Pain

Veterans with chronic headaches had a greater risk of a suicide attempt than that of veterans suffering from chronic neck or back pain, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).

“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
 

‘Surprising’ findings

“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.

“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
 

Veterans with chronic pain

The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.

The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.

The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.

Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.

More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).

“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”

The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).

The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.

Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.

Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.

“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”

No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.

Veterans with chronic headaches had a greater risk of a suicide attempt than that of veterans suffering from chronic neck or back pain, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).

“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
 

‘Surprising’ findings

“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.

“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
 

Veterans with chronic pain

The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.

The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.

The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.

Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.

More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).

“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”

The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).

The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.

Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.

Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.

“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”

No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.

Veterans with chronic headaches had a greater risk of a suicide attempt than that of veterans suffering from chronic neck or back pain, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).

“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
 

‘Surprising’ findings

“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.

“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
 

Veterans with chronic pain

The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.

The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.

The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.

Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.

More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).

“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”

The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).

The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.

Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.

Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.

“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”

No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.

A phase 3, sham-controlled clinical trial of an external trigeminal nerve stimulation (e-TNS) device showed confirmed superiority over a sham device and eliminated the most bothersome migraine symptoms after 2 hours of use. The study also demonstrated that the device, manufactured by Cefaly and cleared in 2020 by the Food and Drug Administration for over-the-counter use, can be safely and effectively used at home.

The study also explored the benefits of 2 hours of use, rather than the 1 hour of use tested in a previous study. “The programming on the device is currently [set to] turn off at 1 hour. As a result of this study, I tell patients if they don’t have adequate relief, and they’re tolerating it, that they can activate it again for a second hour,” Stewart Tepper, MD, said in an interview. Dr. Tepper is a professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., and a coauthor of the study that was presented by Deena Kuruvilla, MD, at the American Headache Society’s 2021 annual meeting. Dr. Kuruvilla is a neurologist and director of the Westport (Conn.) Headache Institute.

The improvements seen over the sham were significant but not overwhelming, according to Deborah Friedman, MD, MPH, professor of neurology and ophthalmology at the University of Texas, Dallas.

“The numbers are not super impressive when you compare them with other devices. I thought it was interesting that the most bothersome symptom went away in a much higher percentage of people than the headache. That was actually pretty impressive,” said Dr. Friedman, who was asked to comment on the study. She also wondered if the sham device may have inadvertently provided a small amount of stimulation, which could explain the smaller than expected efficacy difference. “It just kind of makes me wonder because I would expect to see a larger separation, even though it was statistically significant.”

The study was an overall success according to Dr. Tepper, who noted that the efficacy of pain freedom was comparable with what has been seen with calcitonin gene-related peptide receptor antagonists (gepants), as well as relieving the most bothersome symptom at 2 hours. The device failed to reduce the usage of rescue medication, suggesting that it might be a candidate to combine with rescue medications. “I think the main thing is it works. It works in a sham-controlled trial, it works at home, and it works comparably to acute medication. And it is further evidence that the lack of access is something that needs to be addressed,” said Dr. Tepper.

Access will depend on insurance companies, who have so far been reluctant to pay for the device. Dr. Tepper is not optimistic they will come around on their own. “My feeling about it is that the only way that payers will finally start to cover this is with a concerted, organized advocacy campaign by patients. The analogy is that when the disease-modifying therapies became available for multiple sclerosis, the National MS Society organized the MS patients and they demanded that the payers cover the disease modifying therapies. That’s the kind of intense focus of advocacy that needs to be done for these noninvasive neuromodulation devices,” said Dr. Tepper.

The TEAM study was a double blind, randomized, sham-controlled trial of 538 patients who were asked to use neurostimulation for a 2-hour, continuous session within 4 hours of a moderate to severe migraine accompanied by at least one migraine-associated symptom. At 2 hours, 25.5% of those using the device achieved pain freedom, compared with 18.3% of those using the sham (P < .05). Among those using the device, 56.4% had freedom from most bothersome symptom, compared with 42.3% of those using the sham (P < .01).

Pain relief at 2 hours was more common in the device group (69.5% vs. 55.2%; P < .01), as was absence of all migraine-associated symptoms at 2 hours (42.5% vs. 34.1%; P < .05), sustained pain freedom at 24 hours (22.8% vs. 15.8%; P < .05), and sustained pain relief at 24 hours (45.9% vs. 34.4%; P < .01). There was no statistically significant between-group difference in use of rescue medications.

In the device group, 8.5% of patients experienced an adverse event, versus 2.9% in the sham group (P = .004). The only adverse reaction that occurred more frequently in the device group was forehead paresthesia, discomfort, and burning (3.5% vs. 0.4%; P = .009).

The study was funded by Cefaly. Dr. Tepper and Dr. Friedman have no relevant financial disclosures.

A phase 3, sham-controlled clinical trial of an external trigeminal nerve stimulation (e-TNS) device showed confirmed superiority over a sham device and eliminated the most bothersome migraine symptoms after 2 hours of use. The study also demonstrated that the device, manufactured by Cefaly and cleared in 2020 by the Food and Drug Administration for over-the-counter use, can be safely and effectively used at home.

The study also explored the benefits of 2 hours of use, rather than the 1 hour of use tested in a previous study. “The programming on the device is currently [set to] turn off at 1 hour. As a result of this study, I tell patients if they don’t have adequate relief, and they’re tolerating it, that they can activate it again for a second hour,” Stewart Tepper, MD, said in an interview. Dr. Tepper is a professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., and a coauthor of the study that was presented by Deena Kuruvilla, MD, at the American Headache Society’s 2021 annual meeting. Dr. Kuruvilla is a neurologist and director of the Westport (Conn.) Headache Institute.

The improvements seen over the sham were significant but not overwhelming, according to Deborah Friedman, MD, MPH, professor of neurology and ophthalmology at the University of Texas, Dallas.

“The numbers are not super impressive when you compare them with other devices. I thought it was interesting that the most bothersome symptom went away in a much higher percentage of people than the headache. That was actually pretty impressive,” said Dr. Friedman, who was asked to comment on the study. She also wondered if the sham device may have inadvertently provided a small amount of stimulation, which could explain the smaller than expected efficacy difference. “It just kind of makes me wonder because I would expect to see a larger separation, even though it was statistically significant.”

The study was an overall success according to Dr. Tepper, who noted that the efficacy of pain freedom was comparable with what has been seen with calcitonin gene-related peptide receptor antagonists (gepants), as well as relieving the most bothersome symptom at 2 hours. The device failed to reduce the usage of rescue medication, suggesting that it might be a candidate to combine with rescue medications. “I think the main thing is it works. It works in a sham-controlled trial, it works at home, and it works comparably to acute medication. And it is further evidence that the lack of access is something that needs to be addressed,” said Dr. Tepper.

Access will depend on insurance companies, who have so far been reluctant to pay for the device. Dr. Tepper is not optimistic they will come around on their own. “My feeling about it is that the only way that payers will finally start to cover this is with a concerted, organized advocacy campaign by patients. The analogy is that when the disease-modifying therapies became available for multiple sclerosis, the National MS Society organized the MS patients and they demanded that the payers cover the disease modifying therapies. That’s the kind of intense focus of advocacy that needs to be done for these noninvasive neuromodulation devices,” said Dr. Tepper.

The TEAM study was a double blind, randomized, sham-controlled trial of 538 patients who were asked to use neurostimulation for a 2-hour, continuous session within 4 hours of a moderate to severe migraine accompanied by at least one migraine-associated symptom. At 2 hours, 25.5% of those using the device achieved pain freedom, compared with 18.3% of those using the sham (P < .05). Among those using the device, 56.4% had freedom from most bothersome symptom, compared with 42.3% of those using the sham (P < .01).

Pain relief at 2 hours was more common in the device group (69.5% vs. 55.2%; P < .01), as was absence of all migraine-associated symptoms at 2 hours (42.5% vs. 34.1%; P < .05), sustained pain freedom at 24 hours (22.8% vs. 15.8%; P < .05), and sustained pain relief at 24 hours (45.9% vs. 34.4%; P < .01). There was no statistically significant between-group difference in use of rescue medications.

In the device group, 8.5% of patients experienced an adverse event, versus 2.9% in the sham group (P = .004). The only adverse reaction that occurred more frequently in the device group was forehead paresthesia, discomfort, and burning (3.5% vs. 0.4%; P = .009).

The study was funded by Cefaly. Dr. Tepper and Dr. Friedman have no relevant financial disclosures.

A phase 3, sham-controlled clinical trial of an external trigeminal nerve stimulation (e-TNS) device showed confirmed superiority over a sham device and eliminated the most bothersome migraine symptoms after 2 hours of use. The study also demonstrated that the device, manufactured by Cefaly and cleared in 2020 by the Food and Drug Administration for over-the-counter use, can be safely and effectively used at home.

The study also explored the benefits of 2 hours of use, rather than the 1 hour of use tested in a previous study. “The programming on the device is currently [set to] turn off at 1 hour. As a result of this study, I tell patients if they don’t have adequate relief, and they’re tolerating it, that they can activate it again for a second hour,” Stewart Tepper, MD, said in an interview. Dr. Tepper is a professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., and a coauthor of the study that was presented by Deena Kuruvilla, MD, at the American Headache Society’s 2021 annual meeting. Dr. Kuruvilla is a neurologist and director of the Westport (Conn.) Headache Institute.

The improvements seen over the sham were significant but not overwhelming, according to Deborah Friedman, MD, MPH, professor of neurology and ophthalmology at the University of Texas, Dallas.

“The numbers are not super impressive when you compare them with other devices. I thought it was interesting that the most bothersome symptom went away in a much higher percentage of people than the headache. That was actually pretty impressive,” said Dr. Friedman, who was asked to comment on the study. She also wondered if the sham device may have inadvertently provided a small amount of stimulation, which could explain the smaller than expected efficacy difference. “It just kind of makes me wonder because I would expect to see a larger separation, even though it was statistically significant.”

The study was an overall success according to Dr. Tepper, who noted that the efficacy of pain freedom was comparable with what has been seen with calcitonin gene-related peptide receptor antagonists (gepants), as well as relieving the most bothersome symptom at 2 hours. The device failed to reduce the usage of rescue medication, suggesting that it might be a candidate to combine with rescue medications. “I think the main thing is it works. It works in a sham-controlled trial, it works at home, and it works comparably to acute medication. And it is further evidence that the lack of access is something that needs to be addressed,” said Dr. Tepper.

Access will depend on insurance companies, who have so far been reluctant to pay for the device. Dr. Tepper is not optimistic they will come around on their own. “My feeling about it is that the only way that payers will finally start to cover this is with a concerted, organized advocacy campaign by patients. The analogy is that when the disease-modifying therapies became available for multiple sclerosis, the National MS Society organized the MS patients and they demanded that the payers cover the disease modifying therapies. That’s the kind of intense focus of advocacy that needs to be done for these noninvasive neuromodulation devices,” said Dr. Tepper.

The TEAM study was a double blind, randomized, sham-controlled trial of 538 patients who were asked to use neurostimulation for a 2-hour, continuous session within 4 hours of a moderate to severe migraine accompanied by at least one migraine-associated symptom. At 2 hours, 25.5% of those using the device achieved pain freedom, compared with 18.3% of those using the sham (P < .05). Among those using the device, 56.4% had freedom from most bothersome symptom, compared with 42.3% of those using the sham (P < .01).

Pain relief at 2 hours was more common in the device group (69.5% vs. 55.2%; P < .01), as was absence of all migraine-associated symptoms at 2 hours (42.5% vs. 34.1%; P < .05), sustained pain freedom at 24 hours (22.8% vs. 15.8%; P < .05), and sustained pain relief at 24 hours (45.9% vs. 34.4%; P < .01). There was no statistically significant between-group difference in use of rescue medications.

In the device group, 8.5% of patients experienced an adverse event, versus 2.9% in the sham group (P = .004). The only adverse reaction that occurred more frequently in the device group was forehead paresthesia, discomfort, and burning (3.5% vs. 0.4%; P = .009).

The study was funded by Cefaly. Dr. Tepper and Dr. Friedman have no relevant financial disclosures.

Few patients with migraine receive or are offered preventive therapy, leaving a significant treatment gap in this patient population, new research suggests. Investigators found that among patients with migraine who are eligible for preventive therapy, more than a third were not offered this option. In addition, fewer than 10% were currently taking preventive medication, and an additional 10% had discontinued preventive therapy.

“We confirmed that as of 2012 to 2013 – the years these data were collected from a large, comprehensive survey – gaps in care remained,” said study investigator Stephanie J. Nahas, MD, director of the headache medicine fellowship program, Thomas Jefferson University, Philadelphia. “In this preventive-eligible population, 35% reported never even being offered preventive medication.”

Furthermore, only 28% of patients taking preventive medication experienced a reduction in headache frequency to less than 4 days per month, which is a primary goal of treatment, said Dr. Nahas. Disease burden, as measured with scales of disability and affective comorbidities, remained substantial.

The findings were presented at the American Headache Society’s 2021 annual meeting.


 

Lack of efficacy?

In 2019, the American Headache Society published a position statement recommending that preventive treatment be considered for patients who have migraine and four or more monthly headache days (MHDs), regardless of their level of associated disability. However, previous data suggest few patients who are eligible for preventive treatment receive it. In addition, many who have used preventive medications do not adhere to their regimens because of problems with tolerability, efficacy, or both.

To identify treatment gaps and characterize self-reported use of preventive medications for migraine, the investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a web-based survey conducted in a representative U.S. sample from September 2012 through November 2013.

The survey identified and characterized patients who met modified criteria for migraine consistent with those in ICHD-3. The researchers classified respondents who had migraine and four or more MHDs as potentially eligible for migraine preventive treatment.

The investigators assessed the study population’s use of oral preventive medications, migraine-related disability and burden, willingness to take preventive treatment, and reasons for discontinuation.

Assessments included the Migraine Disability Assessment Questionnaire, the Patient Health Questionnaire–9 for depression, the Generalized Anxiety Disorder 7-Item Scale, the Migraine Specific Quality of Life questionnaire, and the Migraine Symptom Severity Scale.

In all, 16,789 respondents met criteria for migraine, and 6,579 (39.2%) reported having at least four MHDs. The median age of this subgroup that was eligible for preventive treatment was 40.3 years, and approximately 79% were women.

Only 9.8% of respondents who were eligible for preventive medications were currently using an oral preventive medication. Among those who had ever tried an oral preventive medication, 53.6% discontinued it. Efficacy for patients who used medications appeared to be inadequate. Among all current users of preventive treatment, 68.4% continued to have at least four MHDs.

The researchers assessed treatment eligibility among patients not taking preventive medication. Among respondents who had never used a preventive treatment, 35.7% were eligible to receive it. Among all users who had discontinued preventive medication, 61.0% were still eligible to receive it.
 

Attitudes toward injectables

Among respondents who had never used a preventive treatment, 64.3% had zero to three MHDs. The remaining 35.7% had 4-7, 8-14, or 15 or more MHDs. Among current users of preventive treatments, 68.4% had four or more MHDs. Among those who had discontinued preventive treatment, 61.0% had four or more MHDs.

Patients who have never used preventive medication “have substantial management gaps,” said Dr. Nahas. High proportions of these patients have moderate or severe disability (64.7%), depression (43%), and anxiety (39%). The rates of these outcomes are higher in users who discontinued treatment, likely because of confounding by indication, she added.

The prevalence of anxiety was similar between those who currently used, formerly used, or never used preventive medications. However, there were differences between never-users and current or former users with respect to moderate to severe depression (never-users, 43%; current users, 49.4%; discontinued users, 46.5%) and moderate to severe disability (never-users, 64.7%; current users, 80.4%; discontinued users, 78.9%).

In all, 44.6% of those who discontinued preventive therapy reported safety and tolerability problems as reasons for stopping treatment. In addition, 39.7% reported that these medications did not prevent enough headaches. Some patients reported partial or temporary efficacy as a reason for discontinuation. Other reasons were related to health care costs and access and personal preferences. Only 9.2% of patients who discontinued treatment said that their headaches improved enough to stop medication.

The investigators also analyzed respondents’ interest in preventive therapies. Among respondents who had never used preventive therapies, 61.8% of those who were eligible to use them were somewhat or very interested in trying an oral prescription medication for migraine prevention. However, 59.1% of never-users who were eligible for preventive medications were not at all interested, not sure, or needed more information about trying an injectable preventive medication. About 40% were not at all interested in injectables. In general, current users and those who had discontinued medication were more interested in preventive medication, including injectables.
 

‘Disheartening’ discontinuation rates

There are likely multiple reasons for the low rate of migraine prevention treatment, said Dr. Nahas. Many people with migraine never consult a clinician, owing to factors such as stigma, cost, lack of access, and lack of awareness. In addition, patients with migraine are frequently misdiagnosed, she added.

“Other data suggest that only about a quarter of people with episodic migraine and under 5% of people with chronic migraine consult a clinician, receive an accurate diagnosis, and are prescribed appropriate therapy,” said Dr. Nahas.

When the data in this analysis were gathered, public awareness of migraine was much lower than it is today, and injectable migraine therapies had not gained broad acceptance, she noted. Dr. Nahas added it is possible that attitudes toward injectable preventive medications have changed.

“Would people still prefer daily oral medications? We can’t know for sure until we start asking,” she said. In addition, scientific advances and educational outreach have increased clinicians’ awareness, interest, and skill regarding injectable medications, she said.

“I would certainly hope to see that a much greater proportion of preventive-eligible persons with migraine were at least offered, if not currently taking, preventive medication,” said Dr. Nahas. “But there’s no pleasing everyone, so I think we would still see somewhat disheartening discontinuation rates. The reasons for discontinuation, however, might be less typified by concerns about safety and tolerability.”
 

Still relevant

Commenting on the study, Mia Tova Minen, MD, chief of headache research and associate professor of neurology and population health at NYU Langone Health, New York, noted that although CaMEO is an older study, its results are still highly relevant.

“Unfortunately, primary care providers are still uncomfortable prescribing migraine preventive medications, and this accounts for the large percentage [of patients] with migraine who, while eligible for migraine preventive therapy, are not offered it,” she said.

Although the public and primary care physicians are now more aware of preventive treatments for migraine, “the number of people offered migraine preventive medication still needs to increase dramatically,” said Dr. Minen.

The American Academy of Neurology’s guidelines for migraine prevention were published in 2012 and are currently being updated. The updated guidelines may include new evidence for candesartan and emerging treatments, such as melatonin and aerobic exercise.

“It is my hope that primary care providers will become more comfortable prescribing migraine preventive medications sooner,” said Dr. Minen.

The current findings suggest a need for additional ways of educating patients with migraine who are eligible for preventive therapies so that they can advocate for themselves, she added. They also suggest the idea of demanding more insurance coverage of behavioral therapies for migraine, because data indicate that these treatments have long-term efficacy and good safety profiles, said Dr. Minen.
 

An ‘invisible’ disorder

Also commenting on the study, Barbara L. Nye, MD, director of the headache fellowship and codirector of the headache clinic at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said the CaMEO cohort likely is representative of the general population of patients with migraine.

She noted that a significant weakness of the current study is that it examined data collected before the Food and Drug Administration approved monoclonal antibodies and therefore does not reflect patients’ current experience with medications.

“I believe that the attitudes and fears surrounding the use of injectable medication are now likely far less than previously reported, given the positive track record the new generation of once-a-month injectable medications has,” said Dr. Nye.

The findings reinforce the idea that either patients are not talking to their primary care physicians about their headaches and disability or that clinicians are not asking about them, she added. “Both issues are likely linked to the stigma that this disease state has surrounding it. This is an invisible neurological disorder to most,” Dr. Nye said.

The study was sponsored by Allergan before it was acquired by AbbVie. Dr. Nahas has served as a consultant, advisory board member, or speaker for AbbVie/Allergan, Alder/Lundbeck, Amgen/Novartis, Biohaven, Eli Lilly, Impel, Nesos Corp, Supernus, Teva, Theranica, and Zosano. She has not received and will not receive monetary compensation for this research. Dr. Minen has disclosed no relevant financial relationships.
 

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

Few patients with migraine receive or are offered preventive therapy, leaving a significant treatment gap in this patient population, new research suggests. Investigators found that among patients with migraine who are eligible for preventive therapy, more than a third were not offered this option. In addition, fewer than 10% were currently taking preventive medication, and an additional 10% had discontinued preventive therapy.

“We confirmed that as of 2012 to 2013 – the years these data were collected from a large, comprehensive survey – gaps in care remained,” said study investigator Stephanie J. Nahas, MD, director of the headache medicine fellowship program, Thomas Jefferson University, Philadelphia. “In this preventive-eligible population, 35% reported never even being offered preventive medication.”

Furthermore, only 28% of patients taking preventive medication experienced a reduction in headache frequency to less than 4 days per month, which is a primary goal of treatment, said Dr. Nahas. Disease burden, as measured with scales of disability and affective comorbidities, remained substantial.

The findings were presented at the American Headache Society’s 2021 annual meeting.


 

Lack of efficacy?

In 2019, the American Headache Society published a position statement recommending that preventive treatment be considered for patients who have migraine and four or more monthly headache days (MHDs), regardless of their level of associated disability. However, previous data suggest few patients who are eligible for preventive treatment receive it. In addition, many who have used preventive medications do not adhere to their regimens because of problems with tolerability, efficacy, or both.

To identify treatment gaps and characterize self-reported use of preventive medications for migraine, the investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a web-based survey conducted in a representative U.S. sample from September 2012 through November 2013.

The survey identified and characterized patients who met modified criteria for migraine consistent with those in ICHD-3. The researchers classified respondents who had migraine and four or more MHDs as potentially eligible for migraine preventive treatment.

The investigators assessed the study population’s use of oral preventive medications, migraine-related disability and burden, willingness to take preventive treatment, and reasons for discontinuation.

Assessments included the Migraine Disability Assessment Questionnaire, the Patient Health Questionnaire–9 for depression, the Generalized Anxiety Disorder 7-Item Scale, the Migraine Specific Quality of Life questionnaire, and the Migraine Symptom Severity Scale.

In all, 16,789 respondents met criteria for migraine, and 6,579 (39.2%) reported having at least four MHDs. The median age of this subgroup that was eligible for preventive treatment was 40.3 years, and approximately 79% were women.

Only 9.8% of respondents who were eligible for preventive medications were currently using an oral preventive medication. Among those who had ever tried an oral preventive medication, 53.6% discontinued it. Efficacy for patients who used medications appeared to be inadequate. Among all current users of preventive treatment, 68.4% continued to have at least four MHDs.

The researchers assessed treatment eligibility among patients not taking preventive medication. Among respondents who had never used a preventive treatment, 35.7% were eligible to receive it. Among all users who had discontinued preventive medication, 61.0% were still eligible to receive it.
 

Attitudes toward injectables

Among respondents who had never used a preventive treatment, 64.3% had zero to three MHDs. The remaining 35.7% had 4-7, 8-14, or 15 or more MHDs. Among current users of preventive treatments, 68.4% had four or more MHDs. Among those who had discontinued preventive treatment, 61.0% had four or more MHDs.

Patients who have never used preventive medication “have substantial management gaps,” said Dr. Nahas. High proportions of these patients have moderate or severe disability (64.7%), depression (43%), and anxiety (39%). The rates of these outcomes are higher in users who discontinued treatment, likely because of confounding by indication, she added.

The prevalence of anxiety was similar between those who currently used, formerly used, or never used preventive medications. However, there were differences between never-users and current or former users with respect to moderate to severe depression (never-users, 43%; current users, 49.4%; discontinued users, 46.5%) and moderate to severe disability (never-users, 64.7%; current users, 80.4%; discontinued users, 78.9%).

In all, 44.6% of those who discontinued preventive therapy reported safety and tolerability problems as reasons for stopping treatment. In addition, 39.7% reported that these medications did not prevent enough headaches. Some patients reported partial or temporary efficacy as a reason for discontinuation. Other reasons were related to health care costs and access and personal preferences. Only 9.2% of patients who discontinued treatment said that their headaches improved enough to stop medication.

The investigators also analyzed respondents’ interest in preventive therapies. Among respondents who had never used preventive therapies, 61.8% of those who were eligible to use them were somewhat or very interested in trying an oral prescription medication for migraine prevention. However, 59.1% of never-users who were eligible for preventive medications were not at all interested, not sure, or needed more information about trying an injectable preventive medication. About 40% were not at all interested in injectables. In general, current users and those who had discontinued medication were more interested in preventive medication, including injectables.
 

‘Disheartening’ discontinuation rates

There are likely multiple reasons for the low rate of migraine prevention treatment, said Dr. Nahas. Many people with migraine never consult a clinician, owing to factors such as stigma, cost, lack of access, and lack of awareness. In addition, patients with migraine are frequently misdiagnosed, she added.

“Other data suggest that only about a quarter of people with episodic migraine and under 5% of people with chronic migraine consult a clinician, receive an accurate diagnosis, and are prescribed appropriate therapy,” said Dr. Nahas.

When the data in this analysis were gathered, public awareness of migraine was much lower than it is today, and injectable migraine therapies had not gained broad acceptance, she noted. Dr. Nahas added it is possible that attitudes toward injectable preventive medications have changed.

“Would people still prefer daily oral medications? We can’t know for sure until we start asking,” she said. In addition, scientific advances and educational outreach have increased clinicians’ awareness, interest, and skill regarding injectable medications, she said.

“I would certainly hope to see that a much greater proportion of preventive-eligible persons with migraine were at least offered, if not currently taking, preventive medication,” said Dr. Nahas. “But there’s no pleasing everyone, so I think we would still see somewhat disheartening discontinuation rates. The reasons for discontinuation, however, might be less typified by concerns about safety and tolerability.”
 

Still relevant

Commenting on the study, Mia Tova Minen, MD, chief of headache research and associate professor of neurology and population health at NYU Langone Health, New York, noted that although CaMEO is an older study, its results are still highly relevant.

“Unfortunately, primary care providers are still uncomfortable prescribing migraine preventive medications, and this accounts for the large percentage [of patients] with migraine who, while eligible for migraine preventive therapy, are not offered it,” she said.

Although the public and primary care physicians are now more aware of preventive treatments for migraine, “the number of people offered migraine preventive medication still needs to increase dramatically,” said Dr. Minen.

The American Academy of Neurology’s guidelines for migraine prevention were published in 2012 and are currently being updated. The updated guidelines may include new evidence for candesartan and emerging treatments, such as melatonin and aerobic exercise.

“It is my hope that primary care providers will become more comfortable prescribing migraine preventive medications sooner,” said Dr. Minen.

The current findings suggest a need for additional ways of educating patients with migraine who are eligible for preventive therapies so that they can advocate for themselves, she added. They also suggest the idea of demanding more insurance coverage of behavioral therapies for migraine, because data indicate that these treatments have long-term efficacy and good safety profiles, said Dr. Minen.
 

An ‘invisible’ disorder

Also commenting on the study, Barbara L. Nye, MD, director of the headache fellowship and codirector of the headache clinic at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said the CaMEO cohort likely is representative of the general population of patients with migraine.

She noted that a significant weakness of the current study is that it examined data collected before the Food and Drug Administration approved monoclonal antibodies and therefore does not reflect patients’ current experience with medications.

“I believe that the attitudes and fears surrounding the use of injectable medication are now likely far less than previously reported, given the positive track record the new generation of once-a-month injectable medications has,” said Dr. Nye.

The findings reinforce the idea that either patients are not talking to their primary care physicians about their headaches and disability or that clinicians are not asking about them, she added. “Both issues are likely linked to the stigma that this disease state has surrounding it. This is an invisible neurological disorder to most,” Dr. Nye said.

The study was sponsored by Allergan before it was acquired by AbbVie. Dr. Nahas has served as a consultant, advisory board member, or speaker for AbbVie/Allergan, Alder/Lundbeck, Amgen/Novartis, Biohaven, Eli Lilly, Impel, Nesos Corp, Supernus, Teva, Theranica, and Zosano. She has not received and will not receive monetary compensation for this research. Dr. Minen has disclosed no relevant financial relationships.
 

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

Few patients with migraine receive or are offered preventive therapy, leaving a significant treatment gap in this patient population, new research suggests. Investigators found that among patients with migraine who are eligible for preventive therapy, more than a third were not offered this option. In addition, fewer than 10% were currently taking preventive medication, and an additional 10% had discontinued preventive therapy.

“We confirmed that as of 2012 to 2013 – the years these data were collected from a large, comprehensive survey – gaps in care remained,” said study investigator Stephanie J. Nahas, MD, director of the headache medicine fellowship program, Thomas Jefferson University, Philadelphia. “In this preventive-eligible population, 35% reported never even being offered preventive medication.”

Furthermore, only 28% of patients taking preventive medication experienced a reduction in headache frequency to less than 4 days per month, which is a primary goal of treatment, said Dr. Nahas. Disease burden, as measured with scales of disability and affective comorbidities, remained substantial.

The findings were presented at the American Headache Society’s 2021 annual meeting.


 

Lack of efficacy?

In 2019, the American Headache Society published a position statement recommending that preventive treatment be considered for patients who have migraine and four or more monthly headache days (MHDs), regardless of their level of associated disability. However, previous data suggest few patients who are eligible for preventive treatment receive it. In addition, many who have used preventive medications do not adhere to their regimens because of problems with tolerability, efficacy, or both.

To identify treatment gaps and characterize self-reported use of preventive medications for migraine, the investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a web-based survey conducted in a representative U.S. sample from September 2012 through November 2013.

The survey identified and characterized patients who met modified criteria for migraine consistent with those in ICHD-3. The researchers classified respondents who had migraine and four or more MHDs as potentially eligible for migraine preventive treatment.

The investigators assessed the study population’s use of oral preventive medications, migraine-related disability and burden, willingness to take preventive treatment, and reasons for discontinuation.

Assessments included the Migraine Disability Assessment Questionnaire, the Patient Health Questionnaire–9 for depression, the Generalized Anxiety Disorder 7-Item Scale, the Migraine Specific Quality of Life questionnaire, and the Migraine Symptom Severity Scale.

In all, 16,789 respondents met criteria for migraine, and 6,579 (39.2%) reported having at least four MHDs. The median age of this subgroup that was eligible for preventive treatment was 40.3 years, and approximately 79% were women.

Only 9.8% of respondents who were eligible for preventive medications were currently using an oral preventive medication. Among those who had ever tried an oral preventive medication, 53.6% discontinued it. Efficacy for patients who used medications appeared to be inadequate. Among all current users of preventive treatment, 68.4% continued to have at least four MHDs.

The researchers assessed treatment eligibility among patients not taking preventive medication. Among respondents who had never used a preventive treatment, 35.7% were eligible to receive it. Among all users who had discontinued preventive medication, 61.0% were still eligible to receive it.
 

Attitudes toward injectables

Among respondents who had never used a preventive treatment, 64.3% had zero to three MHDs. The remaining 35.7% had 4-7, 8-14, or 15 or more MHDs. Among current users of preventive treatments, 68.4% had four or more MHDs. Among those who had discontinued preventive treatment, 61.0% had four or more MHDs.

Patients who have never used preventive medication “have substantial management gaps,” said Dr. Nahas. High proportions of these patients have moderate or severe disability (64.7%), depression (43%), and anxiety (39%). The rates of these outcomes are higher in users who discontinued treatment, likely because of confounding by indication, she added.

The prevalence of anxiety was similar between those who currently used, formerly used, or never used preventive medications. However, there were differences between never-users and current or former users with respect to moderate to severe depression (never-users, 43%; current users, 49.4%; discontinued users, 46.5%) and moderate to severe disability (never-users, 64.7%; current users, 80.4%; discontinued users, 78.9%).

In all, 44.6% of those who discontinued preventive therapy reported safety and tolerability problems as reasons for stopping treatment. In addition, 39.7% reported that these medications did not prevent enough headaches. Some patients reported partial or temporary efficacy as a reason for discontinuation. Other reasons were related to health care costs and access and personal preferences. Only 9.2% of patients who discontinued treatment said that their headaches improved enough to stop medication.

The investigators also analyzed respondents’ interest in preventive therapies. Among respondents who had never used preventive therapies, 61.8% of those who were eligible to use them were somewhat or very interested in trying an oral prescription medication for migraine prevention. However, 59.1% of never-users who were eligible for preventive medications were not at all interested, not sure, or needed more information about trying an injectable preventive medication. About 40% were not at all interested in injectables. In general, current users and those who had discontinued medication were more interested in preventive medication, including injectables.
 

‘Disheartening’ discontinuation rates

There are likely multiple reasons for the low rate of migraine prevention treatment, said Dr. Nahas. Many people with migraine never consult a clinician, owing to factors such as stigma, cost, lack of access, and lack of awareness. In addition, patients with migraine are frequently misdiagnosed, she added.

“Other data suggest that only about a quarter of people with episodic migraine and under 5% of people with chronic migraine consult a clinician, receive an accurate diagnosis, and are prescribed appropriate therapy,” said Dr. Nahas.

When the data in this analysis were gathered, public awareness of migraine was much lower than it is today, and injectable migraine therapies had not gained broad acceptance, she noted. Dr. Nahas added it is possible that attitudes toward injectable preventive medications have changed.

“Would people still prefer daily oral medications? We can’t know for sure until we start asking,” she said. In addition, scientific advances and educational outreach have increased clinicians’ awareness, interest, and skill regarding injectable medications, she said.

“I would certainly hope to see that a much greater proportion of preventive-eligible persons with migraine were at least offered, if not currently taking, preventive medication,” said Dr. Nahas. “But there’s no pleasing everyone, so I think we would still see somewhat disheartening discontinuation rates. The reasons for discontinuation, however, might be less typified by concerns about safety and tolerability.”
 

Still relevant

Commenting on the study, Mia Tova Minen, MD, chief of headache research and associate professor of neurology and population health at NYU Langone Health, New York, noted that although CaMEO is an older study, its results are still highly relevant.

“Unfortunately, primary care providers are still uncomfortable prescribing migraine preventive medications, and this accounts for the large percentage [of patients] with migraine who, while eligible for migraine preventive therapy, are not offered it,” she said.

Although the public and primary care physicians are now more aware of preventive treatments for migraine, “the number of people offered migraine preventive medication still needs to increase dramatically,” said Dr. Minen.

The American Academy of Neurology’s guidelines for migraine prevention were published in 2012 and are currently being updated. The updated guidelines may include new evidence for candesartan and emerging treatments, such as melatonin and aerobic exercise.

“It is my hope that primary care providers will become more comfortable prescribing migraine preventive medications sooner,” said Dr. Minen.

The current findings suggest a need for additional ways of educating patients with migraine who are eligible for preventive therapies so that they can advocate for themselves, she added. They also suggest the idea of demanding more insurance coverage of behavioral therapies for migraine, because data indicate that these treatments have long-term efficacy and good safety profiles, said Dr. Minen.
 

An ‘invisible’ disorder

Also commenting on the study, Barbara L. Nye, MD, director of the headache fellowship and codirector of the headache clinic at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said the CaMEO cohort likely is representative of the general population of patients with migraine.

She noted that a significant weakness of the current study is that it examined data collected before the Food and Drug Administration approved monoclonal antibodies and therefore does not reflect patients’ current experience with medications.

“I believe that the attitudes and fears surrounding the use of injectable medication are now likely far less than previously reported, given the positive track record the new generation of once-a-month injectable medications has,” said Dr. Nye.

The findings reinforce the idea that either patients are not talking to their primary care physicians about their headaches and disability or that clinicians are not asking about them, she added. “Both issues are likely linked to the stigma that this disease state has surrounding it. This is an invisible neurological disorder to most,” Dr. Nye said.

The study was sponsored by Allergan before it was acquired by AbbVie. Dr. Nahas has served as a consultant, advisory board member, or speaker for AbbVie/Allergan, Alder/Lundbeck, Amgen/Novartis, Biohaven, Eli Lilly, Impel, Nesos Corp, Supernus, Teva, Theranica, and Zosano. She has not received and will not receive monetary compensation for this research. Dr. Minen has disclosed no relevant financial relationships.
 

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

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

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

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

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

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

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

OnabotulinumtoxinA alone provides relief from chronic migraine, and addition of anti-calcitonin gene-related peptide (CGRP) antibodies may boost the benefit, according to a large retrospective analysis. The results lend hope that the combination may be synergistic, according to Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad. Dr. Blumenfeld presented at the American Headache Society’s 2021 annual meeting. The study was published online April 21 in Pain Therapy.

The retrospective analysis showed a 4-day reduction in headache days per month. In contrast, in the pivotal study for erenumab, the most commonly used anti-CGRP antibody among subjects in the study, showed a 2-day benefit in a subanalysis of patients who had failed at least two oral preventives.

There is mechanistic evidence to suggest the two therapies could be synergistic. OnabotulinumtoxinA is believed to inhibit the release of CGRP, and antibodies reduce CGRP levels. OnabotulinumtoxinA prevents activation of C-fibers in the trigeminal sensory afferents, but does not affect A-delta fibers.

On the other hand, most data indicate that the anti-CGRP antibody fremanezumab prevents activation of A-delta but not C-fibers, and a recent review argues that CGRP antibody nonresponders may have migraines driven by C-fibers or other pathways. “Thus, concomitant use of medications blocking the activation of meningeal C-fibers may provide a synergistic effect on the trigeminal nociceptive pathway,” the authors wrote.
 

Study finding match clinical practice

The results of the new study strengthen the case that the combination is effective, though proof would require prospective, randomized trials. “I think that it really gives credibility to what we are seeing in practice, which is that combined therapy often is much better than therapy with onabotulinumtoxinA alone, said Deborah Friedman, MD, MPH, who was asked to comment on the findings. Dr. Friedman is professor of neurology and ophthalmology at the University of Texas, Dallas.

The extra 4 migraine-free days per month is a significant benefit, said Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “It’s an extra month and a half of no disability per year, and that’s on top of what onabotulinumtoxinA does. So it’s really a very important clinical finding,” Dr. Tepper said in an interview.

Improvements with combination therapy

The study was a chart review of 257 patients who started on onabotulinumtoxinA and later initiated anti-CGRP antibody therapy. A total of 104 completed four visits after initiation of anti-CGRP antibody therapy (completers). Before starting any therapy, patients reported an average of 21 headache days per month in the overall group, and 22 among completers. That frequency dropped to 12 in both groups after onabotulinumtoxinA therapy (overall group difference, –9 days; 95% confidence interval, –8 to –11 days; completers group difference, –10; 95% CI, –7 to –12 days).

A total of 77.8% of subjects in the overall cohort took erenumab, 16.3% took galcanezumab, and 5.8% took fremanezumab. In the completers cohort, the percentages were 84.5%, 10.7%, and 4.9%, respectively.

Compared with baseline, both completers and noncompleters had clinically significant improvements in disability, as measured by at least a 5-point improvement in Migraine Disability Assessment (MIDAS) score at the 3-month visit (–5.8 for completers and –6.3 for the overall cohort group), the 6-month visit (–6.6 and –11.1), the 9-month visit (–8.3 and –6.1), and 1 year (–12.7 and –8.4).

At the first visit, 33.0% of completers had at least a 5-point reduction in MIDAS, as did 36.0% of the overall cohort group, and the trend continued at 6 months (39.8% and 45.1%), 9 months (43.7% and 43.7%), and at 1 year (45.3% and 44.8%).

The study was funded by Allergan. Dr. Blumenfeld has served on advisory boards for Aeon, AbbVie, Amgen, Alder, Biohaven, Teva, Supernus, Promius, Eaglet, and Lilly, and has received funding for speaking from AbbVie, Amgen, Pernix, Supernus, Depomed, Avanir, Promius, Teva, Eli Lilly, Lundbeck, Novartis, and Theranica. Dr. Tepper has consulted for Teva. Dr. Friedman has been on the advisory board for Allergan, Amgen, Lundbeck, Eli Lilly, and Teva Pharmaceuticals, and has received grant support from Allergan and Eli Lilly.

OnabotulinumtoxinA alone provides relief from chronic migraine, and addition of anti-calcitonin gene-related peptide (CGRP) antibodies may boost the benefit, according to a large retrospective analysis. The results lend hope that the combination may be synergistic, according to Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad. Dr. Blumenfeld presented at the American Headache Society’s 2021 annual meeting. The study was published online April 21 in Pain Therapy.

The retrospective analysis showed a 4-day reduction in headache days per month. In contrast, in the pivotal study for erenumab, the most commonly used anti-CGRP antibody among subjects in the study, showed a 2-day benefit in a subanalysis of patients who had failed at least two oral preventives.

There is mechanistic evidence to suggest the two therapies could be synergistic. OnabotulinumtoxinA is believed to inhibit the release of CGRP, and antibodies reduce CGRP levels. OnabotulinumtoxinA prevents activation of C-fibers in the trigeminal sensory afferents, but does not affect A-delta fibers.

On the other hand, most data indicate that the anti-CGRP antibody fremanezumab prevents activation of A-delta but not C-fibers, and a recent review argues that CGRP antibody nonresponders may have migraines driven by C-fibers or other pathways. “Thus, concomitant use of medications blocking the activation of meningeal C-fibers may provide a synergistic effect on the trigeminal nociceptive pathway,” the authors wrote.
 

Study finding match clinical practice

The results of the new study strengthen the case that the combination is effective, though proof would require prospective, randomized trials. “I think that it really gives credibility to what we are seeing in practice, which is that combined therapy often is much better than therapy with onabotulinumtoxinA alone, said Deborah Friedman, MD, MPH, who was asked to comment on the findings. Dr. Friedman is professor of neurology and ophthalmology at the University of Texas, Dallas.

The extra 4 migraine-free days per month is a significant benefit, said Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “It’s an extra month and a half of no disability per year, and that’s on top of what onabotulinumtoxinA does. So it’s really a very important clinical finding,” Dr. Tepper said in an interview.

Improvements with combination therapy

The study was a chart review of 257 patients who started on onabotulinumtoxinA and later initiated anti-CGRP antibody therapy. A total of 104 completed four visits after initiation of anti-CGRP antibody therapy (completers). Before starting any therapy, patients reported an average of 21 headache days per month in the overall group, and 22 among completers. That frequency dropped to 12 in both groups after onabotulinumtoxinA therapy (overall group difference, –9 days; 95% confidence interval, –8 to –11 days; completers group difference, –10; 95% CI, –7 to –12 days).

A total of 77.8% of subjects in the overall cohort took erenumab, 16.3% took galcanezumab, and 5.8% took fremanezumab. In the completers cohort, the percentages were 84.5%, 10.7%, and 4.9%, respectively.

Compared with baseline, both completers and noncompleters had clinically significant improvements in disability, as measured by at least a 5-point improvement in Migraine Disability Assessment (MIDAS) score at the 3-month visit (–5.8 for completers and –6.3 for the overall cohort group), the 6-month visit (–6.6 and –11.1), the 9-month visit (–8.3 and –6.1), and 1 year (–12.7 and –8.4).

At the first visit, 33.0% of completers had at least a 5-point reduction in MIDAS, as did 36.0% of the overall cohort group, and the trend continued at 6 months (39.8% and 45.1%), 9 months (43.7% and 43.7%), and at 1 year (45.3% and 44.8%).

The study was funded by Allergan. Dr. Blumenfeld has served on advisory boards for Aeon, AbbVie, Amgen, Alder, Biohaven, Teva, Supernus, Promius, Eaglet, and Lilly, and has received funding for speaking from AbbVie, Amgen, Pernix, Supernus, Depomed, Avanir, Promius, Teva, Eli Lilly, Lundbeck, Novartis, and Theranica. Dr. Tepper has consulted for Teva. Dr. Friedman has been on the advisory board for Allergan, Amgen, Lundbeck, Eli Lilly, and Teva Pharmaceuticals, and has received grant support from Allergan and Eli Lilly.

OnabotulinumtoxinA alone provides relief from chronic migraine, and addition of anti-calcitonin gene-related peptide (CGRP) antibodies may boost the benefit, according to a large retrospective analysis. The results lend hope that the combination may be synergistic, according to Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad. Dr. Blumenfeld presented at the American Headache Society’s 2021 annual meeting. The study was published online April 21 in Pain Therapy.

The retrospective analysis showed a 4-day reduction in headache days per month. In contrast, in the pivotal study for erenumab, the most commonly used anti-CGRP antibody among subjects in the study, showed a 2-day benefit in a subanalysis of patients who had failed at least two oral preventives.

There is mechanistic evidence to suggest the two therapies could be synergistic. OnabotulinumtoxinA is believed to inhibit the release of CGRP, and antibodies reduce CGRP levels. OnabotulinumtoxinA prevents activation of C-fibers in the trigeminal sensory afferents, but does not affect A-delta fibers.

On the other hand, most data indicate that the anti-CGRP antibody fremanezumab prevents activation of A-delta but not C-fibers, and a recent review argues that CGRP antibody nonresponders may have migraines driven by C-fibers or other pathways. “Thus, concomitant use of medications blocking the activation of meningeal C-fibers may provide a synergistic effect on the trigeminal nociceptive pathway,” the authors wrote.
 

Study finding match clinical practice

The results of the new study strengthen the case that the combination is effective, though proof would require prospective, randomized trials. “I think that it really gives credibility to what we are seeing in practice, which is that combined therapy often is much better than therapy with onabotulinumtoxinA alone, said Deborah Friedman, MD, MPH, who was asked to comment on the findings. Dr. Friedman is professor of neurology and ophthalmology at the University of Texas, Dallas.

The extra 4 migraine-free days per month is a significant benefit, said Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “It’s an extra month and a half of no disability per year, and that’s on top of what onabotulinumtoxinA does. So it’s really a very important clinical finding,” Dr. Tepper said in an interview.

Improvements with combination therapy

The study was a chart review of 257 patients who started on onabotulinumtoxinA and later initiated anti-CGRP antibody therapy. A total of 104 completed four visits after initiation of anti-CGRP antibody therapy (completers). Before starting any therapy, patients reported an average of 21 headache days per month in the overall group, and 22 among completers. That frequency dropped to 12 in both groups after onabotulinumtoxinA therapy (overall group difference, –9 days; 95% confidence interval, –8 to –11 days; completers group difference, –10; 95% CI, –7 to –12 days).

A total of 77.8% of subjects in the overall cohort took erenumab, 16.3% took galcanezumab, and 5.8% took fremanezumab. In the completers cohort, the percentages were 84.5%, 10.7%, and 4.9%, respectively.

Compared with baseline, both completers and noncompleters had clinically significant improvements in disability, as measured by at least a 5-point improvement in Migraine Disability Assessment (MIDAS) score at the 3-month visit (–5.8 for completers and –6.3 for the overall cohort group), the 6-month visit (–6.6 and –11.1), the 9-month visit (–8.3 and –6.1), and 1 year (–12.7 and –8.4).

At the first visit, 33.0% of completers had at least a 5-point reduction in MIDAS, as did 36.0% of the overall cohort group, and the trend continued at 6 months (39.8% and 45.1%), 9 months (43.7% and 43.7%), and at 1 year (45.3% and 44.8%).

The study was funded by Allergan. Dr. Blumenfeld has served on advisory boards for Aeon, AbbVie, Amgen, Alder, Biohaven, Teva, Supernus, Promius, Eaglet, and Lilly, and has received funding for speaking from AbbVie, Amgen, Pernix, Supernus, Depomed, Avanir, Promius, Teva, Eli Lilly, Lundbeck, Novartis, and Theranica. Dr. Tepper has consulted for Teva. Dr. Friedman has been on the advisory board for Allergan, Amgen, Lundbeck, Eli Lilly, and Teva Pharmaceuticals, and has received grant support from Allergan and Eli Lilly.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

Obstetric patients whose first language is not English received fewer pain assessments and fewer doses of NSAIDs and oxycodone therapeutic equivalents (OTEs) following cesarean deliveries, according to a retrospective cohort study poster presented at the 2021 annual meeting of the American College of Obstetricians and Gynecologists.

The findings “may indicate language as a barrier for equitable pain management in the postpartum period,” concluded Alison Wiles, MD, a resident at Mount Sinai South Nassau in Oceanside, N.Y., and colleagues. They recommended “scheduled pain assessment and around the clock nonopioid medication administration” as potential ways to reduce the disparities.

“Racial and ethnic disparities in pain management have been well documented in both inpatient and outpatient settings, [and] similar disparities exist within postpartum pain management,” the researchers note in their background material. They also note that non-Hispanic White communities tend to have a higher incidence of opioid misuse.

The researchers conducted a retrospective study of 327 women who had cesarean deliveries from January to June 2018 at Mount Sinai South Nassau Hospital. They excluded women who underwent cesarean hysterectomies, received general anesthesia or patient-controlled analgesia, had a history of drug use, or had allergies to opiates. They did not note incidence of uterine fibroids, endometriosis, or other gynecologic conditions aside from delivery that could cause pain.

The population included a similar number of non-Hispanic White women (n = 111) and Hispanic women (n = 125). The remaining study participants included 32 non-Hispanic Black women and 59 women who were Asian or had another race/ethnicity. The women’s average age was 31, which was statistically similar across all four race/ethnicity groups. Average body mass index of participants was also similar, ranging from 32 to 34.6 kg/m², across all four demographic groups.

About half of all the women (52%) had a previous cesarean delivery, but rates were significantly different between groups: 31% of non-Hispanic Black women and 58% of Hispanic women had a prior cesarean, compared to 50% of non-Hispanic White, Asian, and other women (P < .05).

Half the women in the study overall (50.5%) had public insurance, but the proportion of those with public insurance differed significantly by racial/ethnic demographics. Less than a quarter of Asian/other women (23%) had public insurance, compared with 78% of Hispanic women, 74% of non-Hispanic White women, and 59% of non-Hispanic Black women (P < .0001).

Most of the women (76%) spoke English as their primary language, which included nearly all the women in each demographic group except Hispanic, in which 58% of the women’s primary language was Spanish or another language (P < .0001).

Hispanic patients received an average of 10 pain assessments after their cesarean, compared with an average of 11 in each of the other demographic groups (P = .02). Similarly, English speakers received an average 11 pain assessments, but those who primarily spoke Spanish or another language received 10 (P = .01).

The differences between English and non-English speakers were reflected in who received pain medication even though pain scores were the same between the two groups. English speakers received an average two doses of NSAIDs in the first 24 hours post partum, compared with one dose for those who spoke a primary language other than English (P = .03). At 24-48 hours post partum, those who spoke English received an average three NSAID doses, compared with two among those whose primary language was Spanish or another language (P = .03).

There was no difference between language groups in doses of OTEs in the first 24 hours post partum, but differences did occur on the second day. Women who primarily spoke English received an average four OTE doses in the 24-48 hours post partum, compared with two doses given to women who spoke a non-English primary language (P = .03).

Differences were less consistent or not significant when looking solely at race/ethnicity. All four groups received an average of two NSAID doses in the first 24 hours post partum, but second-day rates varied. Non-Hispanic White women and Asian/other women received an average three doses from 24 to 48 hours post partum while non-Hispanic Black women received one and Hispanic women received two (P = .0009).

No statistically significant differences in OTE doses occurred across the groups in the first 24 hours, but from 24 to 48 hours, the average two doses received by Hispanic women and 3 doses received by Asian women differed significantly from the average four doses received by non-Hispanic White women and the average five doses received by non-Hispanic Black women (P =.01).

“Non-Hispanic Black patients had higher OTE doses and fewer NSAID doses in the 24- to 48-hour postpartum period despite no differences in severe pain scores,” the authors also reported.

“These findings are surprising given the standardized protocols in place designed to assess and treat pain post partum,” Etoi A. Garrison, MD, PhD, an associate professor of maternal-fetal medicine at Vanderbilt University Medical Center, Memphis, Tenn., said in an interview. ” Protocols should minimize bias and promote equitable delivery of care.”

Dr. Garrison said it’s important to find out why these discrepancies exist even when ready access to interpretation services exist in the hospital.

“An important component of health care disparity research is to hear directly from patients themselves about their experiences,” Dr. Garrison said. “Often the patient voice is an overlooked and underappreciated resource. I hope that future iterations of this work include patient perceptions about the adequacy of postpartum care and provide more information about how health care delivery can be tailored to the unique needs of this vulnerable population.”

The authors reported no disclosures. Dr Garrison reported receiving a grant from the State of Tennessee Maternal Mortality Review Committee to Create an Unconscious Bias Faculty Train-the-Trainer Program.

Obstetric patients whose first language is not English received fewer pain assessments and fewer doses of NSAIDs and oxycodone therapeutic equivalents (OTEs) following cesarean deliveries, according to a retrospective cohort study poster presented at the 2021 annual meeting of the American College of Obstetricians and Gynecologists.

The findings “may indicate language as a barrier for equitable pain management in the postpartum period,” concluded Alison Wiles, MD, a resident at Mount Sinai South Nassau in Oceanside, N.Y., and colleagues. They recommended “scheduled pain assessment and around the clock nonopioid medication administration” as potential ways to reduce the disparities.

“Racial and ethnic disparities in pain management have been well documented in both inpatient and outpatient settings, [and] similar disparities exist within postpartum pain management,” the researchers note in their background material. They also note that non-Hispanic White communities tend to have a higher incidence of opioid misuse.

The researchers conducted a retrospective study of 327 women who had cesarean deliveries from January to June 2018 at Mount Sinai South Nassau Hospital. They excluded women who underwent cesarean hysterectomies, received general anesthesia or patient-controlled analgesia, had a history of drug use, or had allergies to opiates. They did not note incidence of uterine fibroids, endometriosis, or other gynecologic conditions aside from delivery that could cause pain.

The population included a similar number of non-Hispanic White women (n = 111) and Hispanic women (n = 125). The remaining study participants included 32 non-Hispanic Black women and 59 women who were Asian or had another race/ethnicity. The women’s average age was 31, which was statistically similar across all four race/ethnicity groups. Average body mass index of participants was also similar, ranging from 32 to 34.6 kg/m², across all four demographic groups.

About half of all the women (52%) had a previous cesarean delivery, but rates were significantly different between groups: 31% of non-Hispanic Black women and 58% of Hispanic women had a prior cesarean, compared to 50% of non-Hispanic White, Asian, and other women (P < .05).

Half the women in the study overall (50.5%) had public insurance, but the proportion of those with public insurance differed significantly by racial/ethnic demographics. Less than a quarter of Asian/other women (23%) had public insurance, compared with 78% of Hispanic women, 74% of non-Hispanic White women, and 59% of non-Hispanic Black women (P < .0001).

Most of the women (76%) spoke English as their primary language, which included nearly all the women in each demographic group except Hispanic, in which 58% of the women’s primary language was Spanish or another language (P < .0001).

Hispanic patients received an average of 10 pain assessments after their cesarean, compared with an average of 11 in each of the other demographic groups (P = .02). Similarly, English speakers received an average 11 pain assessments, but those who primarily spoke Spanish or another language received 10 (P = .01).

The differences between English and non-English speakers were reflected in who received pain medication even though pain scores were the same between the two groups. English speakers received an average two doses of NSAIDs in the first 24 hours post partum, compared with one dose for those who spoke a primary language other than English (P = .03). At 24-48 hours post partum, those who spoke English received an average three NSAID doses, compared with two among those whose primary language was Spanish or another language (P = .03).

There was no difference between language groups in doses of OTEs in the first 24 hours post partum, but differences did occur on the second day. Women who primarily spoke English received an average four OTE doses in the 24-48 hours post partum, compared with two doses given to women who spoke a non-English primary language (P = .03).

Differences were less consistent or not significant when looking solely at race/ethnicity. All four groups received an average of two NSAID doses in the first 24 hours post partum, but second-day rates varied. Non-Hispanic White women and Asian/other women received an average three doses from 24 to 48 hours post partum while non-Hispanic Black women received one and Hispanic women received two (P = .0009).

No statistically significant differences in OTE doses occurred across the groups in the first 24 hours, but from 24 to 48 hours, the average two doses received by Hispanic women and 3 doses received by Asian women differed significantly from the average four doses received by non-Hispanic White women and the average five doses received by non-Hispanic Black women (P =.01).

“Non-Hispanic Black patients had higher OTE doses and fewer NSAID doses in the 24- to 48-hour postpartum period despite no differences in severe pain scores,” the authors also reported.

“These findings are surprising given the standardized protocols in place designed to assess and treat pain post partum,” Etoi A. Garrison, MD, PhD, an associate professor of maternal-fetal medicine at Vanderbilt University Medical Center, Memphis, Tenn., said in an interview. ” Protocols should minimize bias and promote equitable delivery of care.”

Dr. Garrison said it’s important to find out why these discrepancies exist even when ready access to interpretation services exist in the hospital.

“An important component of health care disparity research is to hear directly from patients themselves about their experiences,” Dr. Garrison said. “Often the patient voice is an overlooked and underappreciated resource. I hope that future iterations of this work include patient perceptions about the adequacy of postpartum care and provide more information about how health care delivery can be tailored to the unique needs of this vulnerable population.”

The authors reported no disclosures. Dr Garrison reported receiving a grant from the State of Tennessee Maternal Mortality Review Committee to Create an Unconscious Bias Faculty Train-the-Trainer Program.

Obstetric patients whose first language is not English received fewer pain assessments and fewer doses of NSAIDs and oxycodone therapeutic equivalents (OTEs) following cesarean deliveries, according to a retrospective cohort study poster presented at the 2021 annual meeting of the American College of Obstetricians and Gynecologists.

The findings “may indicate language as a barrier for equitable pain management in the postpartum period,” concluded Alison Wiles, MD, a resident at Mount Sinai South Nassau in Oceanside, N.Y., and colleagues. They recommended “scheduled pain assessment and around the clock nonopioid medication administration” as potential ways to reduce the disparities.

“Racial and ethnic disparities in pain management have been well documented in both inpatient and outpatient settings, [and] similar disparities exist within postpartum pain management,” the researchers note in their background material. They also note that non-Hispanic White communities tend to have a higher incidence of opioid misuse.

The researchers conducted a retrospective study of 327 women who had cesarean deliveries from January to June 2018 at Mount Sinai South Nassau Hospital. They excluded women who underwent cesarean hysterectomies, received general anesthesia or patient-controlled analgesia, had a history of drug use, or had allergies to opiates. They did not note incidence of uterine fibroids, endometriosis, or other gynecologic conditions aside from delivery that could cause pain.

The population included a similar number of non-Hispanic White women (n = 111) and Hispanic women (n = 125). The remaining study participants included 32 non-Hispanic Black women and 59 women who were Asian or had another race/ethnicity. The women’s average age was 31, which was statistically similar across all four race/ethnicity groups. Average body mass index of participants was also similar, ranging from 32 to 34.6 kg/m², across all four demographic groups.

About half of all the women (52%) had a previous cesarean delivery, but rates were significantly different between groups: 31% of non-Hispanic Black women and 58% of Hispanic women had a prior cesarean, compared to 50% of non-Hispanic White, Asian, and other women (P < .05).

Half the women in the study overall (50.5%) had public insurance, but the proportion of those with public insurance differed significantly by racial/ethnic demographics. Less than a quarter of Asian/other women (23%) had public insurance, compared with 78% of Hispanic women, 74% of non-Hispanic White women, and 59% of non-Hispanic Black women (P < .0001).

Most of the women (76%) spoke English as their primary language, which included nearly all the women in each demographic group except Hispanic, in which 58% of the women’s primary language was Spanish or another language (P < .0001).

Hispanic patients received an average of 10 pain assessments after their cesarean, compared with an average of 11 in each of the other demographic groups (P = .02). Similarly, English speakers received an average 11 pain assessments, but those who primarily spoke Spanish or another language received 10 (P = .01).

The differences between English and non-English speakers were reflected in who received pain medication even though pain scores were the same between the two groups. English speakers received an average two doses of NSAIDs in the first 24 hours post partum, compared with one dose for those who spoke a primary language other than English (P = .03). At 24-48 hours post partum, those who spoke English received an average three NSAID doses, compared with two among those whose primary language was Spanish or another language (P = .03).

There was no difference between language groups in doses of OTEs in the first 24 hours post partum, but differences did occur on the second day. Women who primarily spoke English received an average four OTE doses in the 24-48 hours post partum, compared with two doses given to women who spoke a non-English primary language (P = .03).

Differences were less consistent or not significant when looking solely at race/ethnicity. All four groups received an average of two NSAID doses in the first 24 hours post partum, but second-day rates varied. Non-Hispanic White women and Asian/other women received an average three doses from 24 to 48 hours post partum while non-Hispanic Black women received one and Hispanic women received two (P = .0009).

No statistically significant differences in OTE doses occurred across the groups in the first 24 hours, but from 24 to 48 hours, the average two doses received by Hispanic women and 3 doses received by Asian women differed significantly from the average four doses received by non-Hispanic White women and the average five doses received by non-Hispanic Black women (P =.01).

“Non-Hispanic Black patients had higher OTE doses and fewer NSAID doses in the 24- to 48-hour postpartum period despite no differences in severe pain scores,” the authors also reported.

“These findings are surprising given the standardized protocols in place designed to assess and treat pain post partum,” Etoi A. Garrison, MD, PhD, an associate professor of maternal-fetal medicine at Vanderbilt University Medical Center, Memphis, Tenn., said in an interview. ” Protocols should minimize bias and promote equitable delivery of care.”

Dr. Garrison said it’s important to find out why these discrepancies exist even when ready access to interpretation services exist in the hospital.

“An important component of health care disparity research is to hear directly from patients themselves about their experiences,” Dr. Garrison said. “Often the patient voice is an overlooked and underappreciated resource. I hope that future iterations of this work include patient perceptions about the adequacy of postpartum care and provide more information about how health care delivery can be tailored to the unique needs of this vulnerable population.”

The authors reported no disclosures. Dr Garrison reported receiving a grant from the State of Tennessee Maternal Mortality Review Committee to Create an Unconscious Bias Faculty Train-the-Trainer Program.

Study Overview

Objective. To determine the effectiveness of a person-centered intervention (comprising personalized and cocreated treatment plans to promote physical activity) for individuals with chronic widespread pain when delivered with digital eHealth support compared with standard telephone follow-up.

Design. Single-blinded multicenter randomized controlled trial.

Settings and participants. Participants with chronic widespread pain (CWP) who had participated in a pain management program from 2010–16 at 5 primary health care rehabilitation centers in 5 cities or towns in the western part of Sweden were invited to join the study between March 2018 and April 2019 via letter providing information about the intervention. The letter was followed by a phone call 1-2 weeks later to screen for inclusion and exclusion criteria and interest in participating. Additional participants were invited to participate via a newspaper advertisement in 1 of the 5 cities.

Inclusion criteria were Swedish-speaking persons aged 20–65 years with CWP (defined as having pain in both sides of the body, pain above and below the waist, and axial pain for at least 3 months). Exclusion criteria included having other severe somatic or psychiatric disorders, dominating causes of pain other than CWP, or other severe disease interfering with the ability to be physically active, pregnancy, not having access to a smartphone or a computer, inability to speak or understand Swedish, ongoing physiotherapy treatment, and already exercising regularly. Of 716 people initially assessed for eligibility, 425 completed telephone screening, and 139 were randomized (using block randomization) to either the intervention arm (n = 69) or the active control arm (n = 70). Due to the nature of the intervention, it was not possible to blind the participants or the physiotherapist to group allocation. All participants provided written informed consent.

The 2 groups underwent the same first individual meeting with a physiotherapist to cocreate a health plan with physical activities, and, if needed, stress management, based on each participant’s individual preferences, obstacles, goals, and resources. The difference between the groups was the type of follow-up support. Participants in the intervention group had 1 follow-up meeting with the physiotherapist a week after the initial meeting (to review and adjust the health plan as needed) and thereafter were supported through a digital e-health platform (accessed via the participant’s smartphone or computer) during the 6-month follow-up period. Participants were encouraged to access the platform once a week to answer questions regarding their health, and the extent to which they had been able to manage their health plan during the previous week. In addition, the participant and physiotherapist could communicate via the platform as needed. Participants in the active control group had 1 follow-up phone call with the physiotherapist 1 month after the initial meeting (similarly to review and adjust the health plan as needed), and no further contact or support from the physiotherapist during the 6-month follow-up period.

Measures and analysis. The primary outcome measure was pain intensity during the previous week assessed with a 0–100 subscale from the Fibromyalgia Impact Questionnaire (FIQ-pain). Secondary outcome measures included overall health status (via FIQ-total with 10 subscales), global fatigue (via FIQ-fatigue subscale), multidimensional fatigue (via Multidimensional Fatigue Inventory, a 20-item questionnaire rated on a 1-5 Likert scale), clinical manifestations of stress (via Stress and Crisis Inventory, a 35-item questionnaire rated on a 0-4 Likert scale), self-efficacy (via General Self-Efficacy Scale, a 10-item questionnaire rated on a 1-4 Likert scale), health-related quality of life (via Short Form 36, specifically the Physical Component Summary composite score), leisure-time physical activity (via Leisure Time Physical Activity Instrument), and physical function (via 1-min chair-stand test). Additional demographic data on age, pain localization, pharmacological treatment, tobacco use, country of birth, level of education, family status, economic status, work status, sick-leave, and disability pension were collected via a questionnaire.

Between-group differences for changes in outcomes from baseline to 6-month follow-up were calculated using the Mann–Whitney U test for continuous data, and Pearson’s χ² or Fisher’s exact test for categorical data. Significance level was set at 5% with no adjustment for multiple comparisons. All analyses were made according to intention-to-treat by originally assigned group; missing cases were not included in the analysis.

Main results. Participants consisted of primarily middle-age, middle income, educated (> 12 years of education) females, with > 60% of participants working at least part-time (between-group differences in baseline data and demographic data not detailed in the article). A total of 29 participants were lost to follow-up. In the intervention group, lost-to-follow up participants were older, performed fewer hours of physical activity, and had lower mental fatigue at baseline, compared with those who were lost to follow-up in the active control group.

In between-group analyses, there were no significant differences in the primary outcome (pain intensity) from baseline to 6-month follow-up. The only significant difference in secondary outcomes was seen in global fatigue – the active control group improved significantly compared with the intervention group (P = .004).

In the intervention group, 87% of participants used the digital platform. Among these users, 35% contacted the physiotherapist (75% of these communications were health- or study-related issues, 25% were issues with the digital platform), 33% were contacted by the physiotherapist (96% of these communications were about the health plan and physical activity), and 32% never had any contact with the physiotherapist. There was a significant difference in the primary outcome (pain intensity) from baseline to 6-month follow-up between platform users and non-users (P = .03, mean change [SD] 3.8 [19.66] mm vs –20.5 [6.36] mm, respectively).

Conclusion. No significant differences were found between the groups after 6 months (except for a significant decrease in global fatigue in the active control group compared with the intervention group). Further development of interventions to support persons with CWP to maintain regular physical activity is needed.

Commentary

Chronic widespread pain is a disorder characterized by diffuse body pain persisting for at least 3 months.^1-2 It has been associated with lost work productivity, mental ill health, and reduced quality of life. The development of clinically effective and cost-effective pain management strategies for CWP is challenging given the syndrome complexity and heterogenous symptomology. Thus, multimodal, multidisciplinary management is widely advocated, often a combination of education and self-management, with integration of physical, non-pharmacological and pharmacological treatments.^1-3 Of note, physical exercise and cognitive behavioral therapy are 2 non-pharmacological treatments that hold some promise based on available evidence.

The pervasiveness of technology in nearly all aspects of daily life has corresponded with the development of implementation of a wide range of technology-based interventions for health purposes.⁴ Examples of electronic health or eHealth modalities include internet-based, telephone supported, interactive voice-response, videoconferencing, mobile apps, and virtual reality. While the use of technology in chronic pain management interventions has increased in recent years, the literature is still limited, heterogenous, and provides limited evidence on the efficacy of eHealth/digital interventions, let alone which specific modalities are most effective.^4-9

This study adds to the literature as a randomized controlled trial evaluating the effectiveness of a person-centered intervention for individuals with CWP delivered with digital eHealth support compared with standard telephone follow-up. Results showed no significant difference in the primary outcome of pain intensity and nearly all secondary outcomes between the intervention group (supported by the digital platform) and the active control group (supported by a follow-up phone call). Further, intervention participants who did not use the platform improved significantly more in pain intensity than those who used the platform.

While these results imply that digital support does not contribute to improvements in the outcomes measured, it is important these findings are interpreted with caution given the limitations of the study design as well as limitations with the intervention itself. Importantly, while this study was designed as a randomized controlled trial, the authors indicated that it was not possible to blind the participants or the physiotherapist to group allocation, which may have impacted their behaviors while in the study. In addition, as the authors note, an intervention aimed at increasing physical activity should ideally include an objective measure of activity and this was lacking in this study. The use of an actigraphy device for example would have provided objective, continuous data on movement and could have helped assess an important outcome measure – whether participants reached their physical activity goals or had increased their overall physical activity. In the analysis, there was no adjustment for multiple comparisons or use of imputation methods to handle missing values. Further, it was unclear whether differences in baseline data were evaluated and taken into consideration in between-group analyses. Lastly, results are only attributable to the eHealth mode used in this study (digital web-based with limited mechanisms of behavior change and engagement built-in) and thus should not be generalized to all digital/eHealth interventions persons with CWP.

Applications for Clinical Practice

While the results of this study failed to demonstrate significant differences between a physical activity-promoting intervention for persons with CWP with digital follow-up vs telephone follow-up, it remains important to consider person-centered principles when offering CWP management support. In this spirit, clinicians should consider a management approach that takes into account the individual’s knowledge, resources, and barriers, and also actively involves the patient in treatment planning to enhance the patient’s self-efficacy to manage their health. In addition, individual preference for a specific (or combination of) eHealth/digital modality should be considered and used to guide a comprehensive management plan, as well as used as a complementary modality to face-to-face care/support.

Study Overview

Objective. To determine the effectiveness of a person-centered intervention (comprising personalized and cocreated treatment plans to promote physical activity) for individuals with chronic widespread pain when delivered with digital eHealth support compared with standard telephone follow-up.

Design. Single-blinded multicenter randomized controlled trial.

Settings and participants. Participants with chronic widespread pain (CWP) who had participated in a pain management program from 2010–16 at 5 primary health care rehabilitation centers in 5 cities or towns in the western part of Sweden were invited to join the study between March 2018 and April 2019 via letter providing information about the intervention. The letter was followed by a phone call 1-2 weeks later to screen for inclusion and exclusion criteria and interest in participating. Additional participants were invited to participate via a newspaper advertisement in 1 of the 5 cities.

Inclusion criteria were Swedish-speaking persons aged 20–65 years with CWP (defined as having pain in both sides of the body, pain above and below the waist, and axial pain for at least 3 months). Exclusion criteria included having other severe somatic or psychiatric disorders, dominating causes of pain other than CWP, or other severe disease interfering with the ability to be physically active, pregnancy, not having access to a smartphone or a computer, inability to speak or understand Swedish, ongoing physiotherapy treatment, and already exercising regularly. Of 716 people initially assessed for eligibility, 425 completed telephone screening, and 139 were randomized (using block randomization) to either the intervention arm (n = 69) or the active control arm (n = 70). Due to the nature of the intervention, it was not possible to blind the participants or the physiotherapist to group allocation. All participants provided written informed consent.

The 2 groups underwent the same first individual meeting with a physiotherapist to cocreate a health plan with physical activities, and, if needed, stress management, based on each participant’s individual preferences, obstacles, goals, and resources. The difference between the groups was the type of follow-up support. Participants in the intervention group had 1 follow-up meeting with the physiotherapist a week after the initial meeting (to review and adjust the health plan as needed) and thereafter were supported through a digital e-health platform (accessed via the participant’s smartphone or computer) during the 6-month follow-up period. Participants were encouraged to access the platform once a week to answer questions regarding their health, and the extent to which they had been able to manage their health plan during the previous week. In addition, the participant and physiotherapist could communicate via the platform as needed. Participants in the active control group had 1 follow-up phone call with the physiotherapist 1 month after the initial meeting (similarly to review and adjust the health plan as needed), and no further contact or support from the physiotherapist during the 6-month follow-up period.

Measures and analysis. The primary outcome measure was pain intensity during the previous week assessed with a 0–100 subscale from the Fibromyalgia Impact Questionnaire (FIQ-pain). Secondary outcome measures included overall health status (via FIQ-total with 10 subscales), global fatigue (via FIQ-fatigue subscale), multidimensional fatigue (via Multidimensional Fatigue Inventory, a 20-item questionnaire rated on a 1-5 Likert scale), clinical manifestations of stress (via Stress and Crisis Inventory, a 35-item questionnaire rated on a 0-4 Likert scale), self-efficacy (via General Self-Efficacy Scale, a 10-item questionnaire rated on a 1-4 Likert scale), health-related quality of life (via Short Form 36, specifically the Physical Component Summary composite score), leisure-time physical activity (via Leisure Time Physical Activity Instrument), and physical function (via 1-min chair-stand test). Additional demographic data on age, pain localization, pharmacological treatment, tobacco use, country of birth, level of education, family status, economic status, work status, sick-leave, and disability pension were collected via a questionnaire.

Between-group differences for changes in outcomes from baseline to 6-month follow-up were calculated using the Mann–Whitney U test for continuous data, and Pearson’s χ² or Fisher’s exact test for categorical data. Significance level was set at 5% with no adjustment for multiple comparisons. All analyses were made according to intention-to-treat by originally assigned group; missing cases were not included in the analysis.

Main results. Participants consisted of primarily middle-age, middle income, educated (> 12 years of education) females, with > 60% of participants working at least part-time (between-group differences in baseline data and demographic data not detailed in the article). A total of 29 participants were lost to follow-up. In the intervention group, lost-to-follow up participants were older, performed fewer hours of physical activity, and had lower mental fatigue at baseline, compared with those who were lost to follow-up in the active control group.

In between-group analyses, there were no significant differences in the primary outcome (pain intensity) from baseline to 6-month follow-up. The only significant difference in secondary outcomes was seen in global fatigue – the active control group improved significantly compared with the intervention group (P = .004).

In the intervention group, 87% of participants used the digital platform. Among these users, 35% contacted the physiotherapist (75% of these communications were health- or study-related issues, 25% were issues with the digital platform), 33% were contacted by the physiotherapist (96% of these communications were about the health plan and physical activity), and 32% never had any contact with the physiotherapist. There was a significant difference in the primary outcome (pain intensity) from baseline to 6-month follow-up between platform users and non-users (P = .03, mean change [SD] 3.8 [19.66] mm vs –20.5 [6.36] mm, respectively).

Conclusion. No significant differences were found between the groups after 6 months (except for a significant decrease in global fatigue in the active control group compared with the intervention group). Further development of interventions to support persons with CWP to maintain regular physical activity is needed.

Commentary

Chronic widespread pain is a disorder characterized by diffuse body pain persisting for at least 3 months.^1-2 It has been associated with lost work productivity, mental ill health, and reduced quality of life. The development of clinically effective and cost-effective pain management strategies for CWP is challenging given the syndrome complexity and heterogenous symptomology. Thus, multimodal, multidisciplinary management is widely advocated, often a combination of education and self-management, with integration of physical, non-pharmacological and pharmacological treatments.^1-3 Of note, physical exercise and cognitive behavioral therapy are 2 non-pharmacological treatments that hold some promise based on available evidence.

The pervasiveness of technology in nearly all aspects of daily life has corresponded with the development of implementation of a wide range of technology-based interventions for health purposes.⁴ Examples of electronic health or eHealth modalities include internet-based, telephone supported, interactive voice-response, videoconferencing, mobile apps, and virtual reality. While the use of technology in chronic pain management interventions has increased in recent years, the literature is still limited, heterogenous, and provides limited evidence on the efficacy of eHealth/digital interventions, let alone which specific modalities are most effective.^4-9

This study adds to the literature as a randomized controlled trial evaluating the effectiveness of a person-centered intervention for individuals with CWP delivered with digital eHealth support compared with standard telephone follow-up. Results showed no significant difference in the primary outcome of pain intensity and nearly all secondary outcomes between the intervention group (supported by the digital platform) and the active control group (supported by a follow-up phone call). Further, intervention participants who did not use the platform improved significantly more in pain intensity than those who used the platform.

While these results imply that digital support does not contribute to improvements in the outcomes measured, it is important these findings are interpreted with caution given the limitations of the study design as well as limitations with the intervention itself. Importantly, while this study was designed as a randomized controlled trial, the authors indicated that it was not possible to blind the participants or the physiotherapist to group allocation, which may have impacted their behaviors while in the study. In addition, as the authors note, an intervention aimed at increasing physical activity should ideally include an objective measure of activity and this was lacking in this study. The use of an actigraphy device for example would have provided objective, continuous data on movement and could have helped assess an important outcome measure – whether participants reached their physical activity goals or had increased their overall physical activity. In the analysis, there was no adjustment for multiple comparisons or use of imputation methods to handle missing values. Further, it was unclear whether differences in baseline data were evaluated and taken into consideration in between-group analyses. Lastly, results are only attributable to the eHealth mode used in this study (digital web-based with limited mechanisms of behavior change and engagement built-in) and thus should not be generalized to all digital/eHealth interventions persons with CWP.

Applications for Clinical Practice

While the results of this study failed to demonstrate significant differences between a physical activity-promoting intervention for persons with CWP with digital follow-up vs telephone follow-up, it remains important to consider person-centered principles when offering CWP management support. In this spirit, clinicians should consider a management approach that takes into account the individual’s knowledge, resources, and barriers, and also actively involves the patient in treatment planning to enhance the patient’s self-efficacy to manage their health. In addition, individual preference for a specific (or combination of) eHealth/digital modality should be considered and used to guide a comprehensive management plan, as well as used as a complementary modality to face-to-face care/support.

Study Overview

Objective. To determine the effectiveness of a person-centered intervention (comprising personalized and cocreated treatment plans to promote physical activity) for individuals with chronic widespread pain when delivered with digital eHealth support compared with standard telephone follow-up.

Design. Single-blinded multicenter randomized controlled trial.

Settings and participants. Participants with chronic widespread pain (CWP) who had participated in a pain management program from 2010–16 at 5 primary health care rehabilitation centers in 5 cities or towns in the western part of Sweden were invited to join the study between March 2018 and April 2019 via letter providing information about the intervention. The letter was followed by a phone call 1-2 weeks later to screen for inclusion and exclusion criteria and interest in participating. Additional participants were invited to participate via a newspaper advertisement in 1 of the 5 cities.

Inclusion criteria were Swedish-speaking persons aged 20–65 years with CWP (defined as having pain in both sides of the body, pain above and below the waist, and axial pain for at least 3 months). Exclusion criteria included having other severe somatic or psychiatric disorders, dominating causes of pain other than CWP, or other severe disease interfering with the ability to be physically active, pregnancy, not having access to a smartphone or a computer, inability to speak or understand Swedish, ongoing physiotherapy treatment, and already exercising regularly. Of 716 people initially assessed for eligibility, 425 completed telephone screening, and 139 were randomized (using block randomization) to either the intervention arm (n = 69) or the active control arm (n = 70). Due to the nature of the intervention, it was not possible to blind the participants or the physiotherapist to group allocation. All participants provided written informed consent.

The 2 groups underwent the same first individual meeting with a physiotherapist to cocreate a health plan with physical activities, and, if needed, stress management, based on each participant’s individual preferences, obstacles, goals, and resources. The difference between the groups was the type of follow-up support. Participants in the intervention group had 1 follow-up meeting with the physiotherapist a week after the initial meeting (to review and adjust the health plan as needed) and thereafter were supported through a digital e-health platform (accessed via the participant’s smartphone or computer) during the 6-month follow-up period. Participants were encouraged to access the platform once a week to answer questions regarding their health, and the extent to which they had been able to manage their health plan during the previous week. In addition, the participant and physiotherapist could communicate via the platform as needed. Participants in the active control group had 1 follow-up phone call with the physiotherapist 1 month after the initial meeting (similarly to review and adjust the health plan as needed), and no further contact or support from the physiotherapist during the 6-month follow-up period.

Measures and analysis. The primary outcome measure was pain intensity during the previous week assessed with a 0–100 subscale from the Fibromyalgia Impact Questionnaire (FIQ-pain). Secondary outcome measures included overall health status (via FIQ-total with 10 subscales), global fatigue (via FIQ-fatigue subscale), multidimensional fatigue (via Multidimensional Fatigue Inventory, a 20-item questionnaire rated on a 1-5 Likert scale), clinical manifestations of stress (via Stress and Crisis Inventory, a 35-item questionnaire rated on a 0-4 Likert scale), self-efficacy (via General Self-Efficacy Scale, a 10-item questionnaire rated on a 1-4 Likert scale), health-related quality of life (via Short Form 36, specifically the Physical Component Summary composite score), leisure-time physical activity (via Leisure Time Physical Activity Instrument), and physical function (via 1-min chair-stand test). Additional demographic data on age, pain localization, pharmacological treatment, tobacco use, country of birth, level of education, family status, economic status, work status, sick-leave, and disability pension were collected via a questionnaire.

Between-group differences for changes in outcomes from baseline to 6-month follow-up were calculated using the Mann–Whitney U test for continuous data, and Pearson’s χ² or Fisher’s exact test for categorical data. Significance level was set at 5% with no adjustment for multiple comparisons. All analyses were made according to intention-to-treat by originally assigned group; missing cases were not included in the analysis.

Main results. Participants consisted of primarily middle-age, middle income, educated (> 12 years of education) females, with > 60% of participants working at least part-time (between-group differences in baseline data and demographic data not detailed in the article). A total of 29 participants were lost to follow-up. In the intervention group, lost-to-follow up participants were older, performed fewer hours of physical activity, and had lower mental fatigue at baseline, compared with those who were lost to follow-up in the active control group.

In between-group analyses, there were no significant differences in the primary outcome (pain intensity) from baseline to 6-month follow-up. The only significant difference in secondary outcomes was seen in global fatigue – the active control group improved significantly compared with the intervention group (P = .004).

In the intervention group, 87% of participants used the digital platform. Among these users, 35% contacted the physiotherapist (75% of these communications were health- or study-related issues, 25% were issues with the digital platform), 33% were contacted by the physiotherapist (96% of these communications were about the health plan and physical activity), and 32% never had any contact with the physiotherapist. There was a significant difference in the primary outcome (pain intensity) from baseline to 6-month follow-up between platform users and non-users (P = .03, mean change [SD] 3.8 [19.66] mm vs –20.5 [6.36] mm, respectively).

Conclusion. No significant differences were found between the groups after 6 months (except for a significant decrease in global fatigue in the active control group compared with the intervention group). Further development of interventions to support persons with CWP to maintain regular physical activity is needed.

Commentary

Chronic widespread pain is a disorder characterized by diffuse body pain persisting for at least 3 months.^1-2 It has been associated with lost work productivity, mental ill health, and reduced quality of life. The development of clinically effective and cost-effective pain management strategies for CWP is challenging given the syndrome complexity and heterogenous symptomology. Thus, multimodal, multidisciplinary management is widely advocated, often a combination of education and self-management, with integration of physical, non-pharmacological and pharmacological treatments.^1-3 Of note, physical exercise and cognitive behavioral therapy are 2 non-pharmacological treatments that hold some promise based on available evidence.

The pervasiveness of technology in nearly all aspects of daily life has corresponded with the development of implementation of a wide range of technology-based interventions for health purposes.⁴ Examples of electronic health or eHealth modalities include internet-based, telephone supported, interactive voice-response, videoconferencing, mobile apps, and virtual reality. While the use of technology in chronic pain management interventions has increased in recent years, the literature is still limited, heterogenous, and provides limited evidence on the efficacy of eHealth/digital interventions, let alone which specific modalities are most effective.^4-9

This study adds to the literature as a randomized controlled trial evaluating the effectiveness of a person-centered intervention for individuals with CWP delivered with digital eHealth support compared with standard telephone follow-up. Results showed no significant difference in the primary outcome of pain intensity and nearly all secondary outcomes between the intervention group (supported by the digital platform) and the active control group (supported by a follow-up phone call). Further, intervention participants who did not use the platform improved significantly more in pain intensity than those who used the platform.

While these results imply that digital support does not contribute to improvements in the outcomes measured, it is important these findings are interpreted with caution given the limitations of the study design as well as limitations with the intervention itself. Importantly, while this study was designed as a randomized controlled trial, the authors indicated that it was not possible to blind the participants or the physiotherapist to group allocation, which may have impacted their behaviors while in the study. In addition, as the authors note, an intervention aimed at increasing physical activity should ideally include an objective measure of activity and this was lacking in this study. The use of an actigraphy device for example would have provided objective, continuous data on movement and could have helped assess an important outcome measure – whether participants reached their physical activity goals or had increased their overall physical activity. In the analysis, there was no adjustment for multiple comparisons or use of imputation methods to handle missing values. Further, it was unclear whether differences in baseline data were evaluated and taken into consideration in between-group analyses. Lastly, results are only attributable to the eHealth mode used in this study (digital web-based with limited mechanisms of behavior change and engagement built-in) and thus should not be generalized to all digital/eHealth interventions persons with CWP.

Applications for Clinical Practice

While the results of this study failed to demonstrate significant differences between a physical activity-promoting intervention for persons with CWP with digital follow-up vs telephone follow-up, it remains important to consider person-centered principles when offering CWP management support. In this spirit, clinicians should consider a management approach that takes into account the individual’s knowledge, resources, and barriers, and also actively involves the patient in treatment planning to enhance the patient’s self-efficacy to manage their health. In addition, individual preference for a specific (or combination of) eHealth/digital modality should be considered and used to guide a comprehensive management plan, as well as used as a complementary modality to face-to-face care/support.

Recognizing the systemic effects of endometriosis may help doctors better understand the experiences of patients with the disease and guide the approach to diagnosis and treatment, according to the president of the American Society for Reproductive Medicine (ASRM).

Beyond lesions in the pelvis, endometriosis may underlie a range of co-occurring conditions, such as generalized inflammation, fatigue, bowel or bladder dysfunction, depression, and anxiety, Hugh S. Taylor, MD, said at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

Its systemic manifestations may explain why women with endometriosis tend to have a lower body mass index, compared with women without the disease, Dr. Taylor said.

“Stem cells, microRNAs, and generalized inflammation are some of the mechanisms that mediate these long-range effects on distant organ systems,” he said.

Studies have indicated that lesions in the pelvis do not fully explain the disease, and investigators continue to elucidate how “endometriosis that we see in the pelvis is really just the tip of the iceberg,” said Dr. Taylor, chair of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.

Pain, including dysmenorrhea, pelvic pain, and dyspareunia, “can be just as bad with ... stage 1 disease as it can be with stage 4 disease,” he said.

Some patients may not have pain, but have infertility. Other women are asymptomatic, and doctors find endometriosis incidentally.

One common definition of endometriosis – ectopic endometrial glands and stroma predominantly caused by retrograde menstruation – “probably overly simplifies this complex disease,” said Dr. Taylor, who reviewed the current understanding of endometriosis in an article in The Lancet. “The lesions in the pelvis are important. We see them. We treat them. But endometriosis has ... effects throughout the body.”

Dr. Taylor’s research group has shown that stem cells are a potential source of endometriosis. “There are cells from the endometriosis that can be found traveling in the circulation,” but their effects are unclear, he said.

Levels of several microRNAs may be increased or decreased in women with endometriosis, and these altered levels may induce the production of inflammatory cytokines. They also may serve as the basis of a blood test for endometriosis that could be ready for clinical use soon, Dr. Taylor said.

In a mouse model of endometriosis, the disease changes the electrophysiology of the brain and behavior. “We see changes in anxiety induced by endometriosis. We see changes in pain sensitivity induced by endometriosis. And we also see an increase in depression induced by endometriosis in this animal model,” Dr. Taylor said.

Although surgical therapy treats local disease, medical therapy may be needed to treat the systemic manifestations.

During a question-and-answer period after the presentation, Marcelle I. Cedars, MD, asked whether analgesic and hormonal management may be sufficient when a woman has suspected or laparoscopically diagnosed endometriosis and pain is the primary complaint.

“Given the understanding of endometriosis, how would you suggest approaching treatment?” asked Dr. Cedars, president elect of the ASRM and director of the division of reproductive endocrinology and infertility at the University of California, San Francisco.

Analgesic and hormonal therapies remain “the best treatments we have,” Dr. Taylor said. He starts treatment with an oral contraceptive and a nonsteroidal anti-inflammatory medication – “not only for pain relief but to tamp some of the inflammation associated with endometriosis,” he said. If an oral contraceptive does not work, a gonadotropin-releasing hormone antagonist typically is the next step.

Dr. Taylor has disclosed ties to Dot Lab and AbbVie. Dr. Cedars had no disclosures.

jremaly@mdedge.com

Recognizing the systemic effects of endometriosis may help doctors better understand the experiences of patients with the disease and guide the approach to diagnosis and treatment, according to the president of the American Society for Reproductive Medicine (ASRM).

Beyond lesions in the pelvis, endometriosis may underlie a range of co-occurring conditions, such as generalized inflammation, fatigue, bowel or bladder dysfunction, depression, and anxiety, Hugh S. Taylor, MD, said at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

Its systemic manifestations may explain why women with endometriosis tend to have a lower body mass index, compared with women without the disease, Dr. Taylor said.

“Stem cells, microRNAs, and generalized inflammation are some of the mechanisms that mediate these long-range effects on distant organ systems,” he said.

Studies have indicated that lesions in the pelvis do not fully explain the disease, and investigators continue to elucidate how “endometriosis that we see in the pelvis is really just the tip of the iceberg,” said Dr. Taylor, chair of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.

Pain, including dysmenorrhea, pelvic pain, and dyspareunia, “can be just as bad with ... stage 1 disease as it can be with stage 4 disease,” he said.

Some patients may not have pain, but have infertility. Other women are asymptomatic, and doctors find endometriosis incidentally.

One common definition of endometriosis – ectopic endometrial glands and stroma predominantly caused by retrograde menstruation – “probably overly simplifies this complex disease,” said Dr. Taylor, who reviewed the current understanding of endometriosis in an article in The Lancet. “The lesions in the pelvis are important. We see them. We treat them. But endometriosis has ... effects throughout the body.”

Dr. Taylor’s research group has shown that stem cells are a potential source of endometriosis. “There are cells from the endometriosis that can be found traveling in the circulation,” but their effects are unclear, he said.

Levels of several microRNAs may be increased or decreased in women with endometriosis, and these altered levels may induce the production of inflammatory cytokines. They also may serve as the basis of a blood test for endometriosis that could be ready for clinical use soon, Dr. Taylor said.

In a mouse model of endometriosis, the disease changes the electrophysiology of the brain and behavior. “We see changes in anxiety induced by endometriosis. We see changes in pain sensitivity induced by endometriosis. And we also see an increase in depression induced by endometriosis in this animal model,” Dr. Taylor said.

Although surgical therapy treats local disease, medical therapy may be needed to treat the systemic manifestations.

During a question-and-answer period after the presentation, Marcelle I. Cedars, MD, asked whether analgesic and hormonal management may be sufficient when a woman has suspected or laparoscopically diagnosed endometriosis and pain is the primary complaint.

“Given the understanding of endometriosis, how would you suggest approaching treatment?” asked Dr. Cedars, president elect of the ASRM and director of the division of reproductive endocrinology and infertility at the University of California, San Francisco.

Analgesic and hormonal therapies remain “the best treatments we have,” Dr. Taylor said. He starts treatment with an oral contraceptive and a nonsteroidal anti-inflammatory medication – “not only for pain relief but to tamp some of the inflammation associated with endometriosis,” he said. If an oral contraceptive does not work, a gonadotropin-releasing hormone antagonist typically is the next step.

Dr. Taylor has disclosed ties to Dot Lab and AbbVie. Dr. Cedars had no disclosures.

jremaly@mdedge.com

Recognizing the systemic effects of endometriosis may help doctors better understand the experiences of patients with the disease and guide the approach to diagnosis and treatment, according to the president of the American Society for Reproductive Medicine (ASRM).

Beyond lesions in the pelvis, endometriosis may underlie a range of co-occurring conditions, such as generalized inflammation, fatigue, bowel or bladder dysfunction, depression, and anxiety, Hugh S. Taylor, MD, said at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

Its systemic manifestations may explain why women with endometriosis tend to have a lower body mass index, compared with women without the disease, Dr. Taylor said.

“Stem cells, microRNAs, and generalized inflammation are some of the mechanisms that mediate these long-range effects on distant organ systems,” he said.

Studies have indicated that lesions in the pelvis do not fully explain the disease, and investigators continue to elucidate how “endometriosis that we see in the pelvis is really just the tip of the iceberg,” said Dr. Taylor, chair of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn.

Pain, including dysmenorrhea, pelvic pain, and dyspareunia, “can be just as bad with ... stage 1 disease as it can be with stage 4 disease,” he said.

Some patients may not have pain, but have infertility. Other women are asymptomatic, and doctors find endometriosis incidentally.

One common definition of endometriosis – ectopic endometrial glands and stroma predominantly caused by retrograde menstruation – “probably overly simplifies this complex disease,” said Dr. Taylor, who reviewed the current understanding of endometriosis in an article in The Lancet. “The lesions in the pelvis are important. We see them. We treat them. But endometriosis has ... effects throughout the body.”

Dr. Taylor’s research group has shown that stem cells are a potential source of endometriosis. “There are cells from the endometriosis that can be found traveling in the circulation,” but their effects are unclear, he said.

Levels of several microRNAs may be increased or decreased in women with endometriosis, and these altered levels may induce the production of inflammatory cytokines. They also may serve as the basis of a blood test for endometriosis that could be ready for clinical use soon, Dr. Taylor said.

In a mouse model of endometriosis, the disease changes the electrophysiology of the brain and behavior. “We see changes in anxiety induced by endometriosis. We see changes in pain sensitivity induced by endometriosis. And we also see an increase in depression induced by endometriosis in this animal model,” Dr. Taylor said.

Although surgical therapy treats local disease, medical therapy may be needed to treat the systemic manifestations.

During a question-and-answer period after the presentation, Marcelle I. Cedars, MD, asked whether analgesic and hormonal management may be sufficient when a woman has suspected or laparoscopically diagnosed endometriosis and pain is the primary complaint.

“Given the understanding of endometriosis, how would you suggest approaching treatment?” asked Dr. Cedars, president elect of the ASRM and director of the division of reproductive endocrinology and infertility at the University of California, San Francisco.

Analgesic and hormonal therapies remain “the best treatments we have,” Dr. Taylor said. He starts treatment with an oral contraceptive and a nonsteroidal anti-inflammatory medication – “not only for pain relief but to tamp some of the inflammation associated with endometriosis,” he said. If an oral contraceptive does not work, a gonadotropin-releasing hormone antagonist typically is the next step.

Dr. Taylor has disclosed ties to Dot Lab and AbbVie. Dr. Cedars had no disclosures.

jremaly@mdedge.com

Is innervation of cartilage the driving force behind development of osteoarthritis and subsequent pain, or is the degeneration of joints in osteoarthritis affecting nerves and creating pain?

This was the question underpinning a fascinating debate at the OARSI 2021 World Congress, featuring two giants of the OA research community: Anne-Marie Malfait, MD, PhD, professor of medicine in the division of rheumatology at Rush Medical College, Chicago, and Stefan Lohmander, MD, PhD, professor emeritus of orthopedics at Lund (Sweden) University in Sweden.

At stake in the discussion is a greater understanding of the physiological processes that underpin both the development of OA in joints and the experience of pain in patients with OA.

Dr. Lohmander started by pointing out that, while pain is the primary symptoms of OA, it does not always overlap with the physiological processes of the disease, as measured by techniques such as MRI, x-ray, biomarkers, and gait analysis.

“This lack of complete overlap is often a problem when doing our clinical trials,” Dr. Lohmander told the conference, sponsored by Osteoarthritis Research Society International. “When talking about osteoarthritis, we also need to remind ourselves every so often that we are speaking of either the symptoms or the disease and maybe not always the both of them.”

While a healthy joint has pain receptors everywhere but the cartilage, studies have found that the osteoarthritic joint brings blood vessels, sensory nerves, and cells expressing nerve growth factor from the subchondral bone into even noncalcified articular cartilage, he said.

These nociceptor neurons are mechanosensitive, so mechanical injury to the joint triggers inflammation, and the inflammatory proteins themselves act on the nociceptors to generate pain signals in the brain, “so clearly, it is the joint that signals the brain,” Dr. Lohmander said.

However, Dr. Malfait pointed out that there is a body of evidence from animal studies showing that the absence of sensory nerves in joints – either from disease or removal – is associated with the onset or worsening of OA.

“Healthy nerves are really important to ensure healthy joints,” Dr. Malfait said. She said age-related loss of sensory nerves always preceded age-related OA, and was also associated with age-related loss of proprioception and vibratory perception.

Interestingly, animal studies suggest that removing intra-articular nociceptors can actually have a protective effect on the osteoarthritic joint, Dr. Malfait said. Studies in humans who have experienced neurologic lesions also suggests improvement in conditions such as rheumatoid arthritis.

She raised the idea of neurogenic inflammation: that peripheral neurons are releasing vasoactive mediators that contribute to inflammation in tissues. “These nerves and nerve products are talking to all the different cells in the joints,” she said.

Defending his argument that joint pathology is the cause of pain, not the pain causing the joint pathology, Dr. Lohmander gave the example of studies that looked at radiographic abnormalities between two knees of the same patient who also had discordant pain measures for each knee. This research “showed strong association between radiographic osteoarthritis and knee pain, supporting the argument that structural abnormalities cause knee pain,” he said.

Martin van der Esch, PhD, of the Amsterdam University of Applied Sciences, said the debate was one of the highlights of the conference because it addressed such an important and longstanding question in OA.

“Is osteoarthritis leading to a generalized pain, so involvement of the nervous system, but the source – the causality – is in the joint?” he said in an interview. “Or is it the other way around, so that means is there first a problem inside the nervous system – including also the vascular system – and which is presented in the joint?”

It is more than an academic discussion because the conclusions of that could mean different treatment approaches are needed for different groups of patients, and raises the different ways of thinking about OA, he said.

None of the sources for this story declared having any relevant conflicts of interest.

Is innervation of cartilage the driving force behind development of osteoarthritis and subsequent pain, or is the degeneration of joints in osteoarthritis affecting nerves and creating pain?

This was the question underpinning a fascinating debate at the OARSI 2021 World Congress, featuring two giants of the OA research community: Anne-Marie Malfait, MD, PhD, professor of medicine in the division of rheumatology at Rush Medical College, Chicago, and Stefan Lohmander, MD, PhD, professor emeritus of orthopedics at Lund (Sweden) University in Sweden.

At stake in the discussion is a greater understanding of the physiological processes that underpin both the development of OA in joints and the experience of pain in patients with OA.

Dr. Lohmander started by pointing out that, while pain is the primary symptoms of OA, it does not always overlap with the physiological processes of the disease, as measured by techniques such as MRI, x-ray, biomarkers, and gait analysis.

“This lack of complete overlap is often a problem when doing our clinical trials,” Dr. Lohmander told the conference, sponsored by Osteoarthritis Research Society International. “When talking about osteoarthritis, we also need to remind ourselves every so often that we are speaking of either the symptoms or the disease and maybe not always the both of them.”

While a healthy joint has pain receptors everywhere but the cartilage, studies have found that the osteoarthritic joint brings blood vessels, sensory nerves, and cells expressing nerve growth factor from the subchondral bone into even noncalcified articular cartilage, he said.

These nociceptor neurons are mechanosensitive, so mechanical injury to the joint triggers inflammation, and the inflammatory proteins themselves act on the nociceptors to generate pain signals in the brain, “so clearly, it is the joint that signals the brain,” Dr. Lohmander said.

However, Dr. Malfait pointed out that there is a body of evidence from animal studies showing that the absence of sensory nerves in joints – either from disease or removal – is associated with the onset or worsening of OA.

“Healthy nerves are really important to ensure healthy joints,” Dr. Malfait said. She said age-related loss of sensory nerves always preceded age-related OA, and was also associated with age-related loss of proprioception and vibratory perception.

Interestingly, animal studies suggest that removing intra-articular nociceptors can actually have a protective effect on the osteoarthritic joint, Dr. Malfait said. Studies in humans who have experienced neurologic lesions also suggests improvement in conditions such as rheumatoid arthritis.

She raised the idea of neurogenic inflammation: that peripheral neurons are releasing vasoactive mediators that contribute to inflammation in tissues. “These nerves and nerve products are talking to all the different cells in the joints,” she said.

Defending his argument that joint pathology is the cause of pain, not the pain causing the joint pathology, Dr. Lohmander gave the example of studies that looked at radiographic abnormalities between two knees of the same patient who also had discordant pain measures for each knee. This research “showed strong association between radiographic osteoarthritis and knee pain, supporting the argument that structural abnormalities cause knee pain,” he said.

Martin van der Esch, PhD, of the Amsterdam University of Applied Sciences, said the debate was one of the highlights of the conference because it addressed such an important and longstanding question in OA.

“Is osteoarthritis leading to a generalized pain, so involvement of the nervous system, but the source – the causality – is in the joint?” he said in an interview. “Or is it the other way around, so that means is there first a problem inside the nervous system – including also the vascular system – and which is presented in the joint?”

It is more than an academic discussion because the conclusions of that could mean different treatment approaches are needed for different groups of patients, and raises the different ways of thinking about OA, he said.

None of the sources for this story declared having any relevant conflicts of interest.

Is innervation of cartilage the driving force behind development of osteoarthritis and subsequent pain, or is the degeneration of joints in osteoarthritis affecting nerves and creating pain?

This was the question underpinning a fascinating debate at the OARSI 2021 World Congress, featuring two giants of the OA research community: Anne-Marie Malfait, MD, PhD, professor of medicine in the division of rheumatology at Rush Medical College, Chicago, and Stefan Lohmander, MD, PhD, professor emeritus of orthopedics at Lund (Sweden) University in Sweden.

At stake in the discussion is a greater understanding of the physiological processes that underpin both the development of OA in joints and the experience of pain in patients with OA.

Dr. Lohmander started by pointing out that, while pain is the primary symptoms of OA, it does not always overlap with the physiological processes of the disease, as measured by techniques such as MRI, x-ray, biomarkers, and gait analysis.

“This lack of complete overlap is often a problem when doing our clinical trials,” Dr. Lohmander told the conference, sponsored by Osteoarthritis Research Society International. “When talking about osteoarthritis, we also need to remind ourselves every so often that we are speaking of either the symptoms or the disease and maybe not always the both of them.”

While a healthy joint has pain receptors everywhere but the cartilage, studies have found that the osteoarthritic joint brings blood vessels, sensory nerves, and cells expressing nerve growth factor from the subchondral bone into even noncalcified articular cartilage, he said.

These nociceptor neurons are mechanosensitive, so mechanical injury to the joint triggers inflammation, and the inflammatory proteins themselves act on the nociceptors to generate pain signals in the brain, “so clearly, it is the joint that signals the brain,” Dr. Lohmander said.

However, Dr. Malfait pointed out that there is a body of evidence from animal studies showing that the absence of sensory nerves in joints – either from disease or removal – is associated with the onset or worsening of OA.

“Healthy nerves are really important to ensure healthy joints,” Dr. Malfait said. She said age-related loss of sensory nerves always preceded age-related OA, and was also associated with age-related loss of proprioception and vibratory perception.

Interestingly, animal studies suggest that removing intra-articular nociceptors can actually have a protective effect on the osteoarthritic joint, Dr. Malfait said. Studies in humans who have experienced neurologic lesions also suggests improvement in conditions such as rheumatoid arthritis.

She raised the idea of neurogenic inflammation: that peripheral neurons are releasing vasoactive mediators that contribute to inflammation in tissues. “These nerves and nerve products are talking to all the different cells in the joints,” she said.

Defending his argument that joint pathology is the cause of pain, not the pain causing the joint pathology, Dr. Lohmander gave the example of studies that looked at radiographic abnormalities between two knees of the same patient who also had discordant pain measures for each knee. This research “showed strong association between radiographic osteoarthritis and knee pain, supporting the argument that structural abnormalities cause knee pain,” he said.

Martin van der Esch, PhD, of the Amsterdam University of Applied Sciences, said the debate was one of the highlights of the conference because it addressed such an important and longstanding question in OA.

“Is osteoarthritis leading to a generalized pain, so involvement of the nervous system, but the source – the causality – is in the joint?” he said in an interview. “Or is it the other way around, so that means is there first a problem inside the nervous system – including also the vascular system – and which is presented in the joint?”

It is more than an academic discussion because the conclusions of that could mean different treatment approaches are needed for different groups of patients, and raises the different ways of thinking about OA, he said.

None of the sources for this story declared having any relevant conflicts of interest.