Neurology Reviews

NATIONAL HARBOR, MD. – While patients with multiple sclerosis (MS) don’t seem to be more likely to be infected with COVID-19, a neurologist told colleagues, the jury is still out over whether they face a higher mortality risk, especially if they take certain disease-modifying therapies (DMTs)

In regard to MS overall, “the data is conflicting, but any increased risk of mortality appears to be slight. And it appears to be chiefly the consequences associated with comorbidities as seen in other populations,” Joseph R. Berger, MD, said at the John F. Kurtzke Memorial Lecture at the annual meeting of the Consortium of Multiple Sclerosis Centers. “If you’re old, if you’re infirm, if you have obesity and cardiovascular disease and underlying pulmonary disease, you’re at risk of dying yourself. It’s not so much the MS,” said Dr. Berger, professor of neurology at the Hospital of the University of Pennsylvania and chief of the multiple sclerosis division at the University of Pennsylvania, Philadelphia.

Dr. Berger had his own COVID-19 story to tell: He couldn’t attend the conference in person because he was quarantining in Portugal since he tested positive. At press time, he was faring well but had reported 4 days of intense back pain.

In regard to MS and COVID-19, Dr. Berger said consistent research suggests that patients with MS aren’t at higher risk of COVID infection, although hospitalization may be more common. There may be a very small increase in risk of MS relapse in patients with COVID-19, he said, but pseudorelapses are far more common. As for mortality, he highlighted a 2021 pooled analysis of 18 studies with 5,634 patients that suggested they had a crude death rate of 1.97%, standardized lethality ratio of 1.24, and a 24% increased risk of death.

Dr. Berger is skeptical of these findings, however, in light of overall death rate numbers. Early on in the pandemic, the fatality rate in China was estimated at 2.3%.

He said he’s more convinced by a retrospective 2021 German COVID-19 study that compared 551 patients with MS to 156,973 other patients and found lower rates of ICU admission (17.1% in patients with MS vs. 22.7% in those without it), ventilation (9.8% vs. 14.5%), and in‐hospital mortality (11.1% vs. 19.3%).

Meanwhile, a 2021 systematic review found no increase in mortality among 4,310 patients with MS (3% death rate, 20.7% hospitalization), but the death risk was highest among those on no DMTs and those taking anti-CD20 monoclonal antibodies. The COViMS Registry has reported similar findings regarding the anti-CD20 drugs rituximab and ocrelizumab, Dr. Berger noted, and a pooled study of Italian and French data links the monoclonal antibodies to more severe COVID. A 2021 aggregated study also linked the antibodies to increased risk of hospitalization and ICU admission.

“Anti-CD20 monoclonal antibodies appear to increase the risk of hospitalization and perhaps the acquisition of the virus, ICU admission, maybe death,” he said, with rituximab appearing to pose the most risk, followed by ocrelizumab and ofatumumab. “And it appears that the platform [older] therapies may be associated with lesser mortality.”

As for nondrug factors, Dr. Berger said, studies have linked higher risk to age, male sex, and comorbidities.

COVID-19 vaccines are another area of concern, he said. “The recommendation is to administer vaccination prior to the initiation of the anti-CD20s, alemtuzumab, and cladribine, and wait a period of time. Three months is ideal, maybe a little longer, because it appears that the antibody response seems to be best as your CD19 count starts to return.”

Finally, Dr. Berger noted that “passive vaccination” is now available via Evusheld (tixagevimab and cilgavimab) as a preexposure treatment for people with moderate to severe immune compromise who may not mount an effective immune response to COVID-19 vaccination or those who are allergic.

Dr. Berger reported multiple disclosures.

NATIONAL HARBOR, MD. – While patients with multiple sclerosis (MS) don’t seem to be more likely to be infected with COVID-19, a neurologist told colleagues, the jury is still out over whether they face a higher mortality risk, especially if they take certain disease-modifying therapies (DMTs)

In regard to MS overall, “the data is conflicting, but any increased risk of mortality appears to be slight. And it appears to be chiefly the consequences associated with comorbidities as seen in other populations,” Joseph R. Berger, MD, said at the John F. Kurtzke Memorial Lecture at the annual meeting of the Consortium of Multiple Sclerosis Centers. “If you’re old, if you’re infirm, if you have obesity and cardiovascular disease and underlying pulmonary disease, you’re at risk of dying yourself. It’s not so much the MS,” said Dr. Berger, professor of neurology at the Hospital of the University of Pennsylvania and chief of the multiple sclerosis division at the University of Pennsylvania, Philadelphia.

Dr. Berger had his own COVID-19 story to tell: He couldn’t attend the conference in person because he was quarantining in Portugal since he tested positive. At press time, he was faring well but had reported 4 days of intense back pain.

In regard to MS and COVID-19, Dr. Berger said consistent research suggests that patients with MS aren’t at higher risk of COVID infection, although hospitalization may be more common. There may be a very small increase in risk of MS relapse in patients with COVID-19, he said, but pseudorelapses are far more common. As for mortality, he highlighted a 2021 pooled analysis of 18 studies with 5,634 patients that suggested they had a crude death rate of 1.97%, standardized lethality ratio of 1.24, and a 24% increased risk of death.

Dr. Berger is skeptical of these findings, however, in light of overall death rate numbers. Early on in the pandemic, the fatality rate in China was estimated at 2.3%.

He said he’s more convinced by a retrospective 2021 German COVID-19 study that compared 551 patients with MS to 156,973 other patients and found lower rates of ICU admission (17.1% in patients with MS vs. 22.7% in those without it), ventilation (9.8% vs. 14.5%), and in‐hospital mortality (11.1% vs. 19.3%).

Meanwhile, a 2021 systematic review found no increase in mortality among 4,310 patients with MS (3% death rate, 20.7% hospitalization), but the death risk was highest among those on no DMTs and those taking anti-CD20 monoclonal antibodies. The COViMS Registry has reported similar findings regarding the anti-CD20 drugs rituximab and ocrelizumab, Dr. Berger noted, and a pooled study of Italian and French data links the monoclonal antibodies to more severe COVID. A 2021 aggregated study also linked the antibodies to increased risk of hospitalization and ICU admission.

“Anti-CD20 monoclonal antibodies appear to increase the risk of hospitalization and perhaps the acquisition of the virus, ICU admission, maybe death,” he said, with rituximab appearing to pose the most risk, followed by ocrelizumab and ofatumumab. “And it appears that the platform [older] therapies may be associated with lesser mortality.”

As for nondrug factors, Dr. Berger said, studies have linked higher risk to age, male sex, and comorbidities.

COVID-19 vaccines are another area of concern, he said. “The recommendation is to administer vaccination prior to the initiation of the anti-CD20s, alemtuzumab, and cladribine, and wait a period of time. Three months is ideal, maybe a little longer, because it appears that the antibody response seems to be best as your CD19 count starts to return.”

Finally, Dr. Berger noted that “passive vaccination” is now available via Evusheld (tixagevimab and cilgavimab) as a preexposure treatment for people with moderate to severe immune compromise who may not mount an effective immune response to COVID-19 vaccination or those who are allergic.

Dr. Berger reported multiple disclosures.

NATIONAL HARBOR, MD. – While patients with multiple sclerosis (MS) don’t seem to be more likely to be infected with COVID-19, a neurologist told colleagues, the jury is still out over whether they face a higher mortality risk, especially if they take certain disease-modifying therapies (DMTs)

In regard to MS overall, “the data is conflicting, but any increased risk of mortality appears to be slight. And it appears to be chiefly the consequences associated with comorbidities as seen in other populations,” Joseph R. Berger, MD, said at the John F. Kurtzke Memorial Lecture at the annual meeting of the Consortium of Multiple Sclerosis Centers. “If you’re old, if you’re infirm, if you have obesity and cardiovascular disease and underlying pulmonary disease, you’re at risk of dying yourself. It’s not so much the MS,” said Dr. Berger, professor of neurology at the Hospital of the University of Pennsylvania and chief of the multiple sclerosis division at the University of Pennsylvania, Philadelphia.

Dr. Berger had his own COVID-19 story to tell: He couldn’t attend the conference in person because he was quarantining in Portugal since he tested positive. At press time, he was faring well but had reported 4 days of intense back pain.

In regard to MS and COVID-19, Dr. Berger said consistent research suggests that patients with MS aren’t at higher risk of COVID infection, although hospitalization may be more common. There may be a very small increase in risk of MS relapse in patients with COVID-19, he said, but pseudorelapses are far more common. As for mortality, he highlighted a 2021 pooled analysis of 18 studies with 5,634 patients that suggested they had a crude death rate of 1.97%, standardized lethality ratio of 1.24, and a 24% increased risk of death.

Dr. Berger is skeptical of these findings, however, in light of overall death rate numbers. Early on in the pandemic, the fatality rate in China was estimated at 2.3%.

He said he’s more convinced by a retrospective 2021 German COVID-19 study that compared 551 patients with MS to 156,973 other patients and found lower rates of ICU admission (17.1% in patients with MS vs. 22.7% in those without it), ventilation (9.8% vs. 14.5%), and in‐hospital mortality (11.1% vs. 19.3%).

Meanwhile, a 2021 systematic review found no increase in mortality among 4,310 patients with MS (3% death rate, 20.7% hospitalization), but the death risk was highest among those on no DMTs and those taking anti-CD20 monoclonal antibodies. The COViMS Registry has reported similar findings regarding the anti-CD20 drugs rituximab and ocrelizumab, Dr. Berger noted, and a pooled study of Italian and French data links the monoclonal antibodies to more severe COVID. A 2021 aggregated study also linked the antibodies to increased risk of hospitalization and ICU admission.

“Anti-CD20 monoclonal antibodies appear to increase the risk of hospitalization and perhaps the acquisition of the virus, ICU admission, maybe death,” he said, with rituximab appearing to pose the most risk, followed by ocrelizumab and ofatumumab. “And it appears that the platform [older] therapies may be associated with lesser mortality.”

As for nondrug factors, Dr. Berger said, studies have linked higher risk to age, male sex, and comorbidities.

COVID-19 vaccines are another area of concern, he said. “The recommendation is to administer vaccination prior to the initiation of the anti-CD20s, alemtuzumab, and cladribine, and wait a period of time. Three months is ideal, maybe a little longer, because it appears that the antibody response seems to be best as your CD19 count starts to return.”

Finally, Dr. Berger noted that “passive vaccination” is now available via Evusheld (tixagevimab and cilgavimab) as a preexposure treatment for people with moderate to severe immune compromise who may not mount an effective immune response to COVID-19 vaccination or those who are allergic.

Dr. Berger reported multiple disclosures.

Cannabis-based products may control chronic pain as effectively as opioids, but adverse effects are common, and long-term safety remains unknown, according to a new study.

Several other systematic reviews have recently evaluated cannabinoids for treating chronic pain, but the new study’s methodology was “distinct” in “important ways,” leading to “conclusions that differ from other reviews,” according to the authors of the paper published in the Annals of Internal Medicine.

In the new systematic review, synthetic products with high THC:CBD ratios were associated with moderate improvements in pain, whereas plant-based products with comparable THC:CBD ratios offered less relief, said study author Marian S. McDonagh, PharmD, professor of medical informatics and clinical epidemiology, and codirector of the Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues.

Specifically, the investigators stratified cannabis-based interventions according to relative content of two key cannabinoids: THC and CBD. Products were sorted into five categories: high THC:CBD ratio (at least 2:1), comparable THC:CBD ratio (less than 2:1 but more than 1:2), low THC:CBD ratio (no more than 1:2), whole-plant cannabis products, and other cannabinoids.

“In preclinical studies, THC and related compounds have demonstrated analgesic properties, although its psychoactive effects and addiction potential may limit its suitability as an analgesic,” the investigators wrote. “CBD and other cannabinoids may also have some analgesic or anti-inflammatory properties and are not believed to be psychoactive or addictive. Given the variation in analgesic effect with THC and CBD, response may differ according to the ratio of THC to CBD in products used to treat pain.”

The final analysis included 18 randomized placebo-controlled trials involving 1,740 individuals and 7 cohort studies involving 13,095 individuals. Most of the studies were short-term, lasting 1-6 months.

Pain was scored on a ten-point scale, with improvements reported as the mean difference from baseline to post treatment. A mean difference in pain score of 0.5-1.0 was considered a “small effect,” an improvement of 1-2 points was considered a “moderate effect,” and an improvement greater than 2 points was considered a “large effect.”
 

Cannabis-based products with relatively high THC:CBD ratios showed efficacy

Synthetic products with high THC:CBD ratios offered moderate pain relief, based on a mean difference in pain score of –1.15 (95% confidence interval, –1.99 to –0.54), whereas products with comparable THC:CBD ratios were associated with a small effect on pain, with a mean difference of –0.52 (95% CI, –0.95 to –0.19).

According to Dr. McDonagh, treatment response rates were on par with response rates for more conventional treatments, “such as opioids or specific antidepressant drugs,” but data for the cannabis-based products are weaker.

“The amount of evidence available for cannabis-related products is very limited for [response rates], and therefore less certain,” Dr. McDonagh said in an interview. “The average reduction in pain severity is also similar to some other treatments, but we do not have studies directly comparing these treatments to draw conclusions.”

Although the cannabis-based products with relatively high and comparable THC:CBD ratios showed efficacy, they were also associated with “moderate to large increased risk for dizziness, sedation, and nausea,” the investigators wrote, noting that evidence was insufficient to characterize other “key adverse event outcomes” that may occur with long-term use, such as “psychosis, cannabis use disorder, and cognitive deficits.”

For products with low THC:CBD ratios, or without reported THC:CBD ratios, data were too scarce to reach any conclusions at all about safety or efficacy, highlighting the sizable knowledge gaps that remain in the area, the authors said.

“The current evidence on cannabis-related products for chronic pain is quite limited,” Dr. McDonagh said in an interview. “Patients with chronic pain should consult with their doctor to discuss which of the many options for treating chronic pain is best for them to start with.”
 

Patients may face resistance when asking about cannabis

According to Kevin F. Boehnke, PhD, and Daniel J. Clauw, MD, of the anesthesiology department and Chronic Pain and Fatigue Research Center at the University of Michigan, Ann Arbor, patients with chronic pain may face resistance, or even risk of being reported, when asking about cannabis-based products.

“Some physicians cite lack of data as rationale for not engaging with patients who wish to use or currently use cannabis,” Dr. Boehnke and Dr. Clauw wrote in an accompanying editorial. “Such practices may reflect consideration of cannabis solely as a drug of misuse (even in the 37 states where medical cannabis is legal) and requirements to refer patients who disclose or test positive for cannabis use to addiction services or decline to refill opioid prescriptions.”

Instead of shutting patients out, Dr. Boehnke and Dr. Clauw suggested clinicians engage in an “open information exchange” with their patients that focuses on “pragmatism, patient experience, known cannabinoid effects, and harm reduction.” In these conversations, the editorialists recommend noting that, “as with other analgesics, some persons will benefit, and others will not.”

They also offered some practical guidance: “Clinicians could suggest using tinctures (effect onset, 15-45 minutes) for breakthrough pain and edibles or capsules (which last about 6-8 hours) for extended relief. ... The scientific literature suggests that CBD doses could start at 5-10 mg twice daily and increase to 40-50 mg daily, whereas THC doses could start at 0.5-3 mg (initially at night) and increase to 30-40 mg/day.”

David Copenhaver, MD, MPH, clinical professor and chief of the division of pain medicine at UC Davis Health, Sacramento, shared a similar clinical mindset for patients choosing between opioids and cannabis-based products, specifically, CBD.

Compared with opioids, “the side-effect profile for CBD is less and the risk of mortality is less,” Dr. Copenhaver said in an interview, pointing out that nobody, to his knowledge, has ever died from an overdose of cannabis alone, and that CBD doses up to 1,000 mg/kg have been safely tolerated in people. “You present that, and most patients will say, ‘You know, I’d like to give this a try.’”

If so, Dr. Copenhaver makes sure patients know about a nonmedical risk: “The risk to the pocketbook.” Unlike opioids, which are covered under most insurance policies, most cannabis-based therapies are self-pay.

Buyers may get what they pay for, Dr. Copenhaver said, since products vary in quality, as do the dispensaries, from “very modest,” to highly sophisticated, with some even using chromatographic datasets to support the purity of their products.

Dr. Copenhaver steers his patients toward these more sophisticated retailers. Their expertise appears to be paying off, he said, not only in relief for patients, but also in market share. “Survival of the most fit will occur in the marketplace based on the results,” he said. “Unfortunately, some of that information doesn’t get percolated out into the literature.”

For investigators to fully uncover what cannabis-based products can do for chronic pain, Dr. Copenhaver said they need to get as “granular” as the leading dispensaries, which may first require recognition of the “very expansive opportunity” that less-studied cannabinoids may provide.

The study was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators, Dr. Boehnke, Dr. Clauw, and Dr. Copenhaver, disclosed no conflicts of interest.

Cannabis-based products may control chronic pain as effectively as opioids, but adverse effects are common, and long-term safety remains unknown, according to a new study.

Several other systematic reviews have recently evaluated cannabinoids for treating chronic pain, but the new study’s methodology was “distinct” in “important ways,” leading to “conclusions that differ from other reviews,” according to the authors of the paper published in the Annals of Internal Medicine.

In the new systematic review, synthetic products with high THC:CBD ratios were associated with moderate improvements in pain, whereas plant-based products with comparable THC:CBD ratios offered less relief, said study author Marian S. McDonagh, PharmD, professor of medical informatics and clinical epidemiology, and codirector of the Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues.

Specifically, the investigators stratified cannabis-based interventions according to relative content of two key cannabinoids: THC and CBD. Products were sorted into five categories: high THC:CBD ratio (at least 2:1), comparable THC:CBD ratio (less than 2:1 but more than 1:2), low THC:CBD ratio (no more than 1:2), whole-plant cannabis products, and other cannabinoids.

“In preclinical studies, THC and related compounds have demonstrated analgesic properties, although its psychoactive effects and addiction potential may limit its suitability as an analgesic,” the investigators wrote. “CBD and other cannabinoids may also have some analgesic or anti-inflammatory properties and are not believed to be psychoactive or addictive. Given the variation in analgesic effect with THC and CBD, response may differ according to the ratio of THC to CBD in products used to treat pain.”

The final analysis included 18 randomized placebo-controlled trials involving 1,740 individuals and 7 cohort studies involving 13,095 individuals. Most of the studies were short-term, lasting 1-6 months.

Pain was scored on a ten-point scale, with improvements reported as the mean difference from baseline to post treatment. A mean difference in pain score of 0.5-1.0 was considered a “small effect,” an improvement of 1-2 points was considered a “moderate effect,” and an improvement greater than 2 points was considered a “large effect.”
 

Cannabis-based products with relatively high THC:CBD ratios showed efficacy

Synthetic products with high THC:CBD ratios offered moderate pain relief, based on a mean difference in pain score of –1.15 (95% confidence interval, –1.99 to –0.54), whereas products with comparable THC:CBD ratios were associated with a small effect on pain, with a mean difference of –0.52 (95% CI, –0.95 to –0.19).

According to Dr. McDonagh, treatment response rates were on par with response rates for more conventional treatments, “such as opioids or specific antidepressant drugs,” but data for the cannabis-based products are weaker.

“The amount of evidence available for cannabis-related products is very limited for [response rates], and therefore less certain,” Dr. McDonagh said in an interview. “The average reduction in pain severity is also similar to some other treatments, but we do not have studies directly comparing these treatments to draw conclusions.”

Although the cannabis-based products with relatively high and comparable THC:CBD ratios showed efficacy, they were also associated with “moderate to large increased risk for dizziness, sedation, and nausea,” the investigators wrote, noting that evidence was insufficient to characterize other “key adverse event outcomes” that may occur with long-term use, such as “psychosis, cannabis use disorder, and cognitive deficits.”

For products with low THC:CBD ratios, or without reported THC:CBD ratios, data were too scarce to reach any conclusions at all about safety or efficacy, highlighting the sizable knowledge gaps that remain in the area, the authors said.

“The current evidence on cannabis-related products for chronic pain is quite limited,” Dr. McDonagh said in an interview. “Patients with chronic pain should consult with their doctor to discuss which of the many options for treating chronic pain is best for them to start with.”
 

Patients may face resistance when asking about cannabis

According to Kevin F. Boehnke, PhD, and Daniel J. Clauw, MD, of the anesthesiology department and Chronic Pain and Fatigue Research Center at the University of Michigan, Ann Arbor, patients with chronic pain may face resistance, or even risk of being reported, when asking about cannabis-based products.

“Some physicians cite lack of data as rationale for not engaging with patients who wish to use or currently use cannabis,” Dr. Boehnke and Dr. Clauw wrote in an accompanying editorial. “Such practices may reflect consideration of cannabis solely as a drug of misuse (even in the 37 states where medical cannabis is legal) and requirements to refer patients who disclose or test positive for cannabis use to addiction services or decline to refill opioid prescriptions.”

Instead of shutting patients out, Dr. Boehnke and Dr. Clauw suggested clinicians engage in an “open information exchange” with their patients that focuses on “pragmatism, patient experience, known cannabinoid effects, and harm reduction.” In these conversations, the editorialists recommend noting that, “as with other analgesics, some persons will benefit, and others will not.”

They also offered some practical guidance: “Clinicians could suggest using tinctures (effect onset, 15-45 minutes) for breakthrough pain and edibles or capsules (which last about 6-8 hours) for extended relief. ... The scientific literature suggests that CBD doses could start at 5-10 mg twice daily and increase to 40-50 mg daily, whereas THC doses could start at 0.5-3 mg (initially at night) and increase to 30-40 mg/day.”

David Copenhaver, MD, MPH, clinical professor and chief of the division of pain medicine at UC Davis Health, Sacramento, shared a similar clinical mindset for patients choosing between opioids and cannabis-based products, specifically, CBD.

Compared with opioids, “the side-effect profile for CBD is less and the risk of mortality is less,” Dr. Copenhaver said in an interview, pointing out that nobody, to his knowledge, has ever died from an overdose of cannabis alone, and that CBD doses up to 1,000 mg/kg have been safely tolerated in people. “You present that, and most patients will say, ‘You know, I’d like to give this a try.’”

If so, Dr. Copenhaver makes sure patients know about a nonmedical risk: “The risk to the pocketbook.” Unlike opioids, which are covered under most insurance policies, most cannabis-based therapies are self-pay.

Buyers may get what they pay for, Dr. Copenhaver said, since products vary in quality, as do the dispensaries, from “very modest,” to highly sophisticated, with some even using chromatographic datasets to support the purity of their products.

Dr. Copenhaver steers his patients toward these more sophisticated retailers. Their expertise appears to be paying off, he said, not only in relief for patients, but also in market share. “Survival of the most fit will occur in the marketplace based on the results,” he said. “Unfortunately, some of that information doesn’t get percolated out into the literature.”

For investigators to fully uncover what cannabis-based products can do for chronic pain, Dr. Copenhaver said they need to get as “granular” as the leading dispensaries, which may first require recognition of the “very expansive opportunity” that less-studied cannabinoids may provide.

The study was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators, Dr. Boehnke, Dr. Clauw, and Dr. Copenhaver, disclosed no conflicts of interest.

Cannabis-based products may control chronic pain as effectively as opioids, but adverse effects are common, and long-term safety remains unknown, according to a new study.

Several other systematic reviews have recently evaluated cannabinoids for treating chronic pain, but the new study’s methodology was “distinct” in “important ways,” leading to “conclusions that differ from other reviews,” according to the authors of the paper published in the Annals of Internal Medicine.

In the new systematic review, synthetic products with high THC:CBD ratios were associated with moderate improvements in pain, whereas plant-based products with comparable THC:CBD ratios offered less relief, said study author Marian S. McDonagh, PharmD, professor of medical informatics and clinical epidemiology, and codirector of the Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues.

Specifically, the investigators stratified cannabis-based interventions according to relative content of two key cannabinoids: THC and CBD. Products were sorted into five categories: high THC:CBD ratio (at least 2:1), comparable THC:CBD ratio (less than 2:1 but more than 1:2), low THC:CBD ratio (no more than 1:2), whole-plant cannabis products, and other cannabinoids.

“In preclinical studies, THC and related compounds have demonstrated analgesic properties, although its psychoactive effects and addiction potential may limit its suitability as an analgesic,” the investigators wrote. “CBD and other cannabinoids may also have some analgesic or anti-inflammatory properties and are not believed to be psychoactive or addictive. Given the variation in analgesic effect with THC and CBD, response may differ according to the ratio of THC to CBD in products used to treat pain.”

The final analysis included 18 randomized placebo-controlled trials involving 1,740 individuals and 7 cohort studies involving 13,095 individuals. Most of the studies were short-term, lasting 1-6 months.

Pain was scored on a ten-point scale, with improvements reported as the mean difference from baseline to post treatment. A mean difference in pain score of 0.5-1.0 was considered a “small effect,” an improvement of 1-2 points was considered a “moderate effect,” and an improvement greater than 2 points was considered a “large effect.”
 

Cannabis-based products with relatively high THC:CBD ratios showed efficacy

Synthetic products with high THC:CBD ratios offered moderate pain relief, based on a mean difference in pain score of –1.15 (95% confidence interval, –1.99 to –0.54), whereas products with comparable THC:CBD ratios were associated with a small effect on pain, with a mean difference of –0.52 (95% CI, –0.95 to –0.19).

According to Dr. McDonagh, treatment response rates were on par with response rates for more conventional treatments, “such as opioids or specific antidepressant drugs,” but data for the cannabis-based products are weaker.

“The amount of evidence available for cannabis-related products is very limited for [response rates], and therefore less certain,” Dr. McDonagh said in an interview. “The average reduction in pain severity is also similar to some other treatments, but we do not have studies directly comparing these treatments to draw conclusions.”

Although the cannabis-based products with relatively high and comparable THC:CBD ratios showed efficacy, they were also associated with “moderate to large increased risk for dizziness, sedation, and nausea,” the investigators wrote, noting that evidence was insufficient to characterize other “key adverse event outcomes” that may occur with long-term use, such as “psychosis, cannabis use disorder, and cognitive deficits.”

For products with low THC:CBD ratios, or without reported THC:CBD ratios, data were too scarce to reach any conclusions at all about safety or efficacy, highlighting the sizable knowledge gaps that remain in the area, the authors said.

“The current evidence on cannabis-related products for chronic pain is quite limited,” Dr. McDonagh said in an interview. “Patients with chronic pain should consult with their doctor to discuss which of the many options for treating chronic pain is best for them to start with.”
 

Patients may face resistance when asking about cannabis

According to Kevin F. Boehnke, PhD, and Daniel J. Clauw, MD, of the anesthesiology department and Chronic Pain and Fatigue Research Center at the University of Michigan, Ann Arbor, patients with chronic pain may face resistance, or even risk of being reported, when asking about cannabis-based products.

“Some physicians cite lack of data as rationale for not engaging with patients who wish to use or currently use cannabis,” Dr. Boehnke and Dr. Clauw wrote in an accompanying editorial. “Such practices may reflect consideration of cannabis solely as a drug of misuse (even in the 37 states where medical cannabis is legal) and requirements to refer patients who disclose or test positive for cannabis use to addiction services or decline to refill opioid prescriptions.”

Instead of shutting patients out, Dr. Boehnke and Dr. Clauw suggested clinicians engage in an “open information exchange” with their patients that focuses on “pragmatism, patient experience, known cannabinoid effects, and harm reduction.” In these conversations, the editorialists recommend noting that, “as with other analgesics, some persons will benefit, and others will not.”

They also offered some practical guidance: “Clinicians could suggest using tinctures (effect onset, 15-45 minutes) for breakthrough pain and edibles or capsules (which last about 6-8 hours) for extended relief. ... The scientific literature suggests that CBD doses could start at 5-10 mg twice daily and increase to 40-50 mg daily, whereas THC doses could start at 0.5-3 mg (initially at night) and increase to 30-40 mg/day.”

David Copenhaver, MD, MPH, clinical professor and chief of the division of pain medicine at UC Davis Health, Sacramento, shared a similar clinical mindset for patients choosing between opioids and cannabis-based products, specifically, CBD.

Compared with opioids, “the side-effect profile for CBD is less and the risk of mortality is less,” Dr. Copenhaver said in an interview, pointing out that nobody, to his knowledge, has ever died from an overdose of cannabis alone, and that CBD doses up to 1,000 mg/kg have been safely tolerated in people. “You present that, and most patients will say, ‘You know, I’d like to give this a try.’”

If so, Dr. Copenhaver makes sure patients know about a nonmedical risk: “The risk to the pocketbook.” Unlike opioids, which are covered under most insurance policies, most cannabis-based therapies are self-pay.

Buyers may get what they pay for, Dr. Copenhaver said, since products vary in quality, as do the dispensaries, from “very modest,” to highly sophisticated, with some even using chromatographic datasets to support the purity of their products.

Dr. Copenhaver steers his patients toward these more sophisticated retailers. Their expertise appears to be paying off, he said, not only in relief for patients, but also in market share. “Survival of the most fit will occur in the marketplace based on the results,” he said. “Unfortunately, some of that information doesn’t get percolated out into the literature.”

For investigators to fully uncover what cannabis-based products can do for chronic pain, Dr. Copenhaver said they need to get as “granular” as the leading dispensaries, which may first require recognition of the “very expansive opportunity” that less-studied cannabinoids may provide.

The study was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators, Dr. Boehnke, Dr. Clauw, and Dr. Copenhaver, disclosed no conflicts of interest.

NATIONAL HARBOR, MD. -- Over 25 years of clinical research, phase 3 trials of approved disease-modifying therapies (DMTs) for multiple sclerosis (MS) were overwhelmingly made up of White subjects, a new analysis finds, and many studies failed to report percentages of non-White subjects at all. Researchers also found that the websites of multiple major drug manufacturers don’t include any trial data about how medications may affect people of different races and ethnicities.

It’s clear that “non-White participants are significantly underreported and unrepresented,” said study corresponding author and Dell Medical School/The University of Texas at Austin neurologist Leorah Freeman, MD, PhD, in an interview. “Despite the globalization of MS trials over time, we do not see that trials are enrolling more diverse populations.”

The study was presented at the annual meeting of the Consortium of Multiple Sclerosis Centers and published in Neurology.

“The lack of diversity in MS research is something that has been sporadically discussed in the past. By conducting this systematic review of MS phase 3 trials, we wanted to put numbers on this issue and review the evidence systematically,” Dr. Freeman said. “By doing so, we hoped to raise awareness about the problem of underreporting and underrepresentation of non-White participants in trials so that we, as a community involved in MS research, can start having the difficult conversations needed for change to occur.”
 

25 years of clinical research

The researchers reviewed 44 phase 3 studies from 1995-2020 that represented 45 trials. “We wanted to capture data from the very first global trials being conducted for the approval of MS DMTs, and the first was published in 1995,” Dr. Freeman said. “We were interested in understanding the impact of trial globalization over a long period of time on diversity of enrollment.”

The studies include trials of mainstays of MS treatment such as interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, diroximel fumarate, fingolimod, natalizumab, and others.

The researchers found that 17 (37.8%) of the trials did not report race or ethnicity, 14 (31.1%) reported race and ethnicity as proportion of White participants only, and 14 (31.1%) reported 2 or more races/ethnicities.

Of the 28 trials with racial breakdowns, the median percentage of White participants was 93.8% (range 78.5-99.6% across 28 studies), 1.9% for Black participants (range 0.1-8.1% across 14 studies), and 0.5% for Asian participants (range 0.1-14.5% across 11 studies).

The studies often failed to account for non-White subjects even though “Black people, in particular, have been shown to have a more severe disease course,” Dr. Freeman said.

A 2022 study of more than 2.6 million Southern California adults finds that prevalence of MS was similar among White and Black people at about 230 per 100,000. “Taken together with previous studies, these findings indicate that the burden of MS in the United States Black community has long been underrecognized,” the researchers wrote.

According to Dr. Freeman, it’s unclear why the studies were so dominated by White subjects. “Lack of awareness about the importance of this information likely explains why this information often goes unreported.”

She highlighted the TOWER (teriflunomide) and DEFINE and CONFIRM (dimethyl fumarate) studies as positive examples. “We noted the inclusion of trial sites in Asia and consequently a higher representation of Asian people with MS in those trials. We felt these studies were examples of how trial globalization can support better representation of underrepresented groups.”

And she noted that the ongoing CHIMES trial is examining the use of ocrelizumab in Black and Hispanic people with MS. “This study was designed in partnership with MS patients and advocacy groups to bridge gaps in clinical trial participation in these communities,” she said. “Innovative strategies were developed to increase participation of Black and Hispanic patients in this trial.”
 

What should happen next?

Going forward, Dr. Freeman said, “MS researchers, DMT manufacturers, sponsors, and publishers need to set better standards for racial and ethnic representation and reporting in trial publications.”

In an interview, epidemiologist Luisa N. Borrell, DDS, PhD, a professor who studies race and medicine at City University of New York, said the new study is valid and useful. She noted that it reflects the findings of a 2022 analysis of more than 20,500 clinical trials in the U.S. from 2000-2020: Only 43% reported racial/ethnic breakdowns, and the subjects were much more White than the population at large.

Possible reasons for the disparity include distrust among possible participants and lack of health literacy, she said, which are both “modifiable issues.”

Dr. Borrell added: “Clinical trials should aim to recruit populations affected by the outcome of interest. That would allow for the intervention to effectively treat those who need it the most. Moreover, the lack of diversity of trials brings issues of generalizability and transportability of the findings.”

No funding is reported. Dr. Freeman and some of the other study authors report various disclosures.

NATIONAL HARBOR, MD. -- Over 25 years of clinical research, phase 3 trials of approved disease-modifying therapies (DMTs) for multiple sclerosis (MS) were overwhelmingly made up of White subjects, a new analysis finds, and many studies failed to report percentages of non-White subjects at all. Researchers also found that the websites of multiple major drug manufacturers don’t include any trial data about how medications may affect people of different races and ethnicities.

It’s clear that “non-White participants are significantly underreported and unrepresented,” said study corresponding author and Dell Medical School/The University of Texas at Austin neurologist Leorah Freeman, MD, PhD, in an interview. “Despite the globalization of MS trials over time, we do not see that trials are enrolling more diverse populations.”

The study was presented at the annual meeting of the Consortium of Multiple Sclerosis Centers and published in Neurology.

“The lack of diversity in MS research is something that has been sporadically discussed in the past. By conducting this systematic review of MS phase 3 trials, we wanted to put numbers on this issue and review the evidence systematically,” Dr. Freeman said. “By doing so, we hoped to raise awareness about the problem of underreporting and underrepresentation of non-White participants in trials so that we, as a community involved in MS research, can start having the difficult conversations needed for change to occur.”
 

25 years of clinical research

The researchers reviewed 44 phase 3 studies from 1995-2020 that represented 45 trials. “We wanted to capture data from the very first global trials being conducted for the approval of MS DMTs, and the first was published in 1995,” Dr. Freeman said. “We were interested in understanding the impact of trial globalization over a long period of time on diversity of enrollment.”

The studies include trials of mainstays of MS treatment such as interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, diroximel fumarate, fingolimod, natalizumab, and others.

The researchers found that 17 (37.8%) of the trials did not report race or ethnicity, 14 (31.1%) reported race and ethnicity as proportion of White participants only, and 14 (31.1%) reported 2 or more races/ethnicities.

Of the 28 trials with racial breakdowns, the median percentage of White participants was 93.8% (range 78.5-99.6% across 28 studies), 1.9% for Black participants (range 0.1-8.1% across 14 studies), and 0.5% for Asian participants (range 0.1-14.5% across 11 studies).

The studies often failed to account for non-White subjects even though “Black people, in particular, have been shown to have a more severe disease course,” Dr. Freeman said.

A 2022 study of more than 2.6 million Southern California adults finds that prevalence of MS was similar among White and Black people at about 230 per 100,000. “Taken together with previous studies, these findings indicate that the burden of MS in the United States Black community has long been underrecognized,” the researchers wrote.

According to Dr. Freeman, it’s unclear why the studies were so dominated by White subjects. “Lack of awareness about the importance of this information likely explains why this information often goes unreported.”

She highlighted the TOWER (teriflunomide) and DEFINE and CONFIRM (dimethyl fumarate) studies as positive examples. “We noted the inclusion of trial sites in Asia and consequently a higher representation of Asian people with MS in those trials. We felt these studies were examples of how trial globalization can support better representation of underrepresented groups.”

And she noted that the ongoing CHIMES trial is examining the use of ocrelizumab in Black and Hispanic people with MS. “This study was designed in partnership with MS patients and advocacy groups to bridge gaps in clinical trial participation in these communities,” she said. “Innovative strategies were developed to increase participation of Black and Hispanic patients in this trial.”
 

What should happen next?

Going forward, Dr. Freeman said, “MS researchers, DMT manufacturers, sponsors, and publishers need to set better standards for racial and ethnic representation and reporting in trial publications.”

In an interview, epidemiologist Luisa N. Borrell, DDS, PhD, a professor who studies race and medicine at City University of New York, said the new study is valid and useful. She noted that it reflects the findings of a 2022 analysis of more than 20,500 clinical trials in the U.S. from 2000-2020: Only 43% reported racial/ethnic breakdowns, and the subjects were much more White than the population at large.

Possible reasons for the disparity include distrust among possible participants and lack of health literacy, she said, which are both “modifiable issues.”

Dr. Borrell added: “Clinical trials should aim to recruit populations affected by the outcome of interest. That would allow for the intervention to effectively treat those who need it the most. Moreover, the lack of diversity of trials brings issues of generalizability and transportability of the findings.”

No funding is reported. Dr. Freeman and some of the other study authors report various disclosures.

NATIONAL HARBOR, MD. -- Over 25 years of clinical research, phase 3 trials of approved disease-modifying therapies (DMTs) for multiple sclerosis (MS) were overwhelmingly made up of White subjects, a new analysis finds, and many studies failed to report percentages of non-White subjects at all. Researchers also found that the websites of multiple major drug manufacturers don’t include any trial data about how medications may affect people of different races and ethnicities.

It’s clear that “non-White participants are significantly underreported and unrepresented,” said study corresponding author and Dell Medical School/The University of Texas at Austin neurologist Leorah Freeman, MD, PhD, in an interview. “Despite the globalization of MS trials over time, we do not see that trials are enrolling more diverse populations.”

The study was presented at the annual meeting of the Consortium of Multiple Sclerosis Centers and published in Neurology.

“The lack of diversity in MS research is something that has been sporadically discussed in the past. By conducting this systematic review of MS phase 3 trials, we wanted to put numbers on this issue and review the evidence systematically,” Dr. Freeman said. “By doing so, we hoped to raise awareness about the problem of underreporting and underrepresentation of non-White participants in trials so that we, as a community involved in MS research, can start having the difficult conversations needed for change to occur.”
 

25 years of clinical research

The researchers reviewed 44 phase 3 studies from 1995-2020 that represented 45 trials. “We wanted to capture data from the very first global trials being conducted for the approval of MS DMTs, and the first was published in 1995,” Dr. Freeman said. “We were interested in understanding the impact of trial globalization over a long period of time on diversity of enrollment.”

The studies include trials of mainstays of MS treatment such as interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, diroximel fumarate, fingolimod, natalizumab, and others.

The researchers found that 17 (37.8%) of the trials did not report race or ethnicity, 14 (31.1%) reported race and ethnicity as proportion of White participants only, and 14 (31.1%) reported 2 or more races/ethnicities.

Of the 28 trials with racial breakdowns, the median percentage of White participants was 93.8% (range 78.5-99.6% across 28 studies), 1.9% for Black participants (range 0.1-8.1% across 14 studies), and 0.5% for Asian participants (range 0.1-14.5% across 11 studies).

The studies often failed to account for non-White subjects even though “Black people, in particular, have been shown to have a more severe disease course,” Dr. Freeman said.

A 2022 study of more than 2.6 million Southern California adults finds that prevalence of MS was similar among White and Black people at about 230 per 100,000. “Taken together with previous studies, these findings indicate that the burden of MS in the United States Black community has long been underrecognized,” the researchers wrote.

According to Dr. Freeman, it’s unclear why the studies were so dominated by White subjects. “Lack of awareness about the importance of this information likely explains why this information often goes unreported.”

She highlighted the TOWER (teriflunomide) and DEFINE and CONFIRM (dimethyl fumarate) studies as positive examples. “We noted the inclusion of trial sites in Asia and consequently a higher representation of Asian people with MS in those trials. We felt these studies were examples of how trial globalization can support better representation of underrepresented groups.”

And she noted that the ongoing CHIMES trial is examining the use of ocrelizumab in Black and Hispanic people with MS. “This study was designed in partnership with MS patients and advocacy groups to bridge gaps in clinical trial participation in these communities,” she said. “Innovative strategies were developed to increase participation of Black and Hispanic patients in this trial.”
 

What should happen next?

Going forward, Dr. Freeman said, “MS researchers, DMT manufacturers, sponsors, and publishers need to set better standards for racial and ethnic representation and reporting in trial publications.”

In an interview, epidemiologist Luisa N. Borrell, DDS, PhD, a professor who studies race and medicine at City University of New York, said the new study is valid and useful. She noted that it reflects the findings of a 2022 analysis of more than 20,500 clinical trials in the U.S. from 2000-2020: Only 43% reported racial/ethnic breakdowns, and the subjects were much more White than the population at large.

Possible reasons for the disparity include distrust among possible participants and lack of health literacy, she said, which are both “modifiable issues.”

Dr. Borrell added: “Clinical trials should aim to recruit populations affected by the outcome of interest. That would allow for the intervention to effectively treat those who need it the most. Moreover, the lack of diversity of trials brings issues of generalizability and transportability of the findings.”

No funding is reported. Dr. Freeman and some of the other study authors report various disclosures.

A novel blood-based assay could one day be used to diagnose Parkinson’s disease and possibly other chronic inflammatory conditions, according to investigators. In addition to being highly accurate, the assay, which detects changes in expression of cytochrome P450s, is faster and easier to perform than other Parkinson’s disease assays under investigation, reported lead author Kohei Ihara, PhD, of Kobe University, Japan, and colleagues.

“Effective diagnostic systems and biomarkers for patients without subjective motor symptoms have not yet been established,” the investigators wrote in Nature Scientific Reports. “Consequently, the poor diagnostic options for Parkinson’s disease delay the development of therapeutic approaches and medication. Therefore, the development of efficient diagnostic systems and biomarkers is crucial for overcoming Parkinson’s disease.”

According to Dr. Ihara and colleagues, various cytochrome P450 expression patterns and associated serum metabolites correlate with chronic conditions, making them possible markers of disease. To detect these changes, they developed the present assay. It relies upon recombinant P450s expressed on the surface of Escherichia coli. By mixing the E. coli with serum and Vivid, a fluorescent substrate, the investigators can measure “the inhibition rate of the Vivid decomposition reaction” that was driven by “serum metabolites associated with P450s,” revealing underlying expression and, if present, disease.

After some promising initial experiments with mouse models of ulcerative colitis and diabetes, Dr. Ihara and colleagues focused on a rat model of Parkinson’s disease. Evaluating inhibition rates associated with four P450s revealed area-under-the-curve (AUC) values of 0.814-0.914. Two of those P450s were also associated with progression of disease symptoms.

“Therefore, we concluded that the P450 inhibition assay could discriminate between Parkinson’s disease model rats and control rats,” the investigators wrote.

Next, the investigators tested the approach with a case-control study involving 20 patients with Parkinson’s disease and 20 healthy volunteers. Twelve P450s were analyzed, three of which revealed significant differences between patients with Parkinson’s disease and controls, with AUCs ranging from 0.740-0.775. Each of the three P450 enzymes also correlated significantly with stage of disease on the Hoehn & Yahr scale, although severity and frequency of symptoms were not reported.

To increase accuracy of the technique, the investigators developed a logistic regression model using two of the three P450s, generating an AUC of 0.910. Further testing showed that the P450 inhibition assay could distinguish between patients with Parkinson’s disease and Alzheimer’s disease, as well as other chronic inflammatory diseases.

“The P450 inhibition assay is easier to perform and is faster than other assays because this assay does not require pretreatment, such as purification of exosomes, and it involves a single enzymatic reaction,” the investigators wrote, suggesting that the assay may be suitable for real-world diagnosis.
 

‘Promising’ findings need replication

According to Douglas Galasko, MD, a neurologist and professor of neurosciences at UC San Diego Health, the reported accuracy of the assay “seems spectacular,” and the findings are “promising,” but they need to be replicated, “particularly in early-stage patients where the diagnosis [of Parkinson’s disease] is more difficult and important to make.” In practice, the assay would likely see greatest usage for “early diagnosis or diagnosis of unusual or challenging cases,” so accuracy testing needs to be conducted in this setting, he said.

Dr. Galasko, who was not involved in the study, predicted that liquid biopsy for detecting Parkinson’s disease is unlikely to hit the clinic floor anytime soon. “We’re not really close with blood-based biomarkers for Parkinson’s disease,” he said, “unlike the situation for Alzheimer’s disease, where there are several promising blood-based biomarkers.”

For diagnosing Parkinson’s disease, Dr. Galasko suggested that assays using skin biopsies to measure alpha-synuclein accumulation may be closer to approval.

The study was supported by JSPS KAKENHI Grant Number 20K20223 and the Sumitomo Electric Industries Group Corporate Social Responsibility Foundation. The investigators disclosed no conflicts of interest.

A novel blood-based assay could one day be used to diagnose Parkinson’s disease and possibly other chronic inflammatory conditions, according to investigators. In addition to being highly accurate, the assay, which detects changes in expression of cytochrome P450s, is faster and easier to perform than other Parkinson’s disease assays under investigation, reported lead author Kohei Ihara, PhD, of Kobe University, Japan, and colleagues.

“Effective diagnostic systems and biomarkers for patients without subjective motor symptoms have not yet been established,” the investigators wrote in Nature Scientific Reports. “Consequently, the poor diagnostic options for Parkinson’s disease delay the development of therapeutic approaches and medication. Therefore, the development of efficient diagnostic systems and biomarkers is crucial for overcoming Parkinson’s disease.”

According to Dr. Ihara and colleagues, various cytochrome P450 expression patterns and associated serum metabolites correlate with chronic conditions, making them possible markers of disease. To detect these changes, they developed the present assay. It relies upon recombinant P450s expressed on the surface of Escherichia coli. By mixing the E. coli with serum and Vivid, a fluorescent substrate, the investigators can measure “the inhibition rate of the Vivid decomposition reaction” that was driven by “serum metabolites associated with P450s,” revealing underlying expression and, if present, disease.

After some promising initial experiments with mouse models of ulcerative colitis and diabetes, Dr. Ihara and colleagues focused on a rat model of Parkinson’s disease. Evaluating inhibition rates associated with four P450s revealed area-under-the-curve (AUC) values of 0.814-0.914. Two of those P450s were also associated with progression of disease symptoms.

“Therefore, we concluded that the P450 inhibition assay could discriminate between Parkinson’s disease model rats and control rats,” the investigators wrote.

Next, the investigators tested the approach with a case-control study involving 20 patients with Parkinson’s disease and 20 healthy volunteers. Twelve P450s were analyzed, three of which revealed significant differences between patients with Parkinson’s disease and controls, with AUCs ranging from 0.740-0.775. Each of the three P450 enzymes also correlated significantly with stage of disease on the Hoehn & Yahr scale, although severity and frequency of symptoms were not reported.

To increase accuracy of the technique, the investigators developed a logistic regression model using two of the three P450s, generating an AUC of 0.910. Further testing showed that the P450 inhibition assay could distinguish between patients with Parkinson’s disease and Alzheimer’s disease, as well as other chronic inflammatory diseases.

“The P450 inhibition assay is easier to perform and is faster than other assays because this assay does not require pretreatment, such as purification of exosomes, and it involves a single enzymatic reaction,” the investigators wrote, suggesting that the assay may be suitable for real-world diagnosis.
 

‘Promising’ findings need replication

According to Douglas Galasko, MD, a neurologist and professor of neurosciences at UC San Diego Health, the reported accuracy of the assay “seems spectacular,” and the findings are “promising,” but they need to be replicated, “particularly in early-stage patients where the diagnosis [of Parkinson’s disease] is more difficult and important to make.” In practice, the assay would likely see greatest usage for “early diagnosis or diagnosis of unusual or challenging cases,” so accuracy testing needs to be conducted in this setting, he said.

Dr. Galasko, who was not involved in the study, predicted that liquid biopsy for detecting Parkinson’s disease is unlikely to hit the clinic floor anytime soon. “We’re not really close with blood-based biomarkers for Parkinson’s disease,” he said, “unlike the situation for Alzheimer’s disease, where there are several promising blood-based biomarkers.”

For diagnosing Parkinson’s disease, Dr. Galasko suggested that assays using skin biopsies to measure alpha-synuclein accumulation may be closer to approval.

The study was supported by JSPS KAKENHI Grant Number 20K20223 and the Sumitomo Electric Industries Group Corporate Social Responsibility Foundation. The investigators disclosed no conflicts of interest.

A novel blood-based assay could one day be used to diagnose Parkinson’s disease and possibly other chronic inflammatory conditions, according to investigators. In addition to being highly accurate, the assay, which detects changes in expression of cytochrome P450s, is faster and easier to perform than other Parkinson’s disease assays under investigation, reported lead author Kohei Ihara, PhD, of Kobe University, Japan, and colleagues.

“Effective diagnostic systems and biomarkers for patients without subjective motor symptoms have not yet been established,” the investigators wrote in Nature Scientific Reports. “Consequently, the poor diagnostic options for Parkinson’s disease delay the development of therapeutic approaches and medication. Therefore, the development of efficient diagnostic systems and biomarkers is crucial for overcoming Parkinson’s disease.”

According to Dr. Ihara and colleagues, various cytochrome P450 expression patterns and associated serum metabolites correlate with chronic conditions, making them possible markers of disease. To detect these changes, they developed the present assay. It relies upon recombinant P450s expressed on the surface of Escherichia coli. By mixing the E. coli with serum and Vivid, a fluorescent substrate, the investigators can measure “the inhibition rate of the Vivid decomposition reaction” that was driven by “serum metabolites associated with P450s,” revealing underlying expression and, if present, disease.

After some promising initial experiments with mouse models of ulcerative colitis and diabetes, Dr. Ihara and colleagues focused on a rat model of Parkinson’s disease. Evaluating inhibition rates associated with four P450s revealed area-under-the-curve (AUC) values of 0.814-0.914. Two of those P450s were also associated with progression of disease symptoms.

“Therefore, we concluded that the P450 inhibition assay could discriminate between Parkinson’s disease model rats and control rats,” the investigators wrote.

Next, the investigators tested the approach with a case-control study involving 20 patients with Parkinson’s disease and 20 healthy volunteers. Twelve P450s were analyzed, three of which revealed significant differences between patients with Parkinson’s disease and controls, with AUCs ranging from 0.740-0.775. Each of the three P450 enzymes also correlated significantly with stage of disease on the Hoehn & Yahr scale, although severity and frequency of symptoms were not reported.

To increase accuracy of the technique, the investigators developed a logistic regression model using two of the three P450s, generating an AUC of 0.910. Further testing showed that the P450 inhibition assay could distinguish between patients with Parkinson’s disease and Alzheimer’s disease, as well as other chronic inflammatory diseases.

“The P450 inhibition assay is easier to perform and is faster than other assays because this assay does not require pretreatment, such as purification of exosomes, and it involves a single enzymatic reaction,” the investigators wrote, suggesting that the assay may be suitable for real-world diagnosis.
 

‘Promising’ findings need replication

According to Douglas Galasko, MD, a neurologist and professor of neurosciences at UC San Diego Health, the reported accuracy of the assay “seems spectacular,” and the findings are “promising,” but they need to be replicated, “particularly in early-stage patients where the diagnosis [of Parkinson’s disease] is more difficult and important to make.” In practice, the assay would likely see greatest usage for “early diagnosis or diagnosis of unusual or challenging cases,” so accuracy testing needs to be conducted in this setting, he said.

Dr. Galasko, who was not involved in the study, predicted that liquid biopsy for detecting Parkinson’s disease is unlikely to hit the clinic floor anytime soon. “We’re not really close with blood-based biomarkers for Parkinson’s disease,” he said, “unlike the situation for Alzheimer’s disease, where there are several promising blood-based biomarkers.”

For diagnosing Parkinson’s disease, Dr. Galasko suggested that assays using skin biopsies to measure alpha-synuclein accumulation may be closer to approval.

The study was supported by JSPS KAKENHI Grant Number 20K20223 and the Sumitomo Electric Industries Group Corporate Social Responsibility Foundation. The investigators disclosed no conflicts of interest.

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/mcL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

“It’s meaningless to just go by some recommendation covering time since the last treatment,” study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor at Uppsala University, both in Sweden, told this news organization.

“It’s misleading and potentially harmful for patients,” Dr. Burman said.

The findings were published online  in JAMA Network Open.
 

Finding the cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/mcL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs. 2.1; P = .002).
 

Close monitoring needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/mcL, versus 51/mcL for the remainder of the cohort (P < .001).

A cutoff value of 40/mcL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible – but that they should hold off on receiving a booster until their B-cell counts reach 40/mcL.

Regarding when a clinician should re-vaccinate, “the results from our study strongly suggest that you should not do that right away or just follow some generic guideline,” Dr. Burman said.

“You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/mcL” he added.

Dr. Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.
 

Too soon for B-cell measures?

Commenting for this news organization, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the United States for treating MS.

“Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines,” said Dr. Fox, who was not involved with the research.

“Given the unknown efficacy of these extended intervals, I don’t think we’re at the point of making management recommendations based upon B-cell counts,” he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Dr. Burman reported.

“Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class,” Dr. Fox said.

“Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data,” he noted.

“At this point, we don’t know which decisions were right or wrong, but I certainly don’t think we should judge clinicians for making decisions the best they could.”

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Dr. Burman reported no relevant financial relationships. Dr. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

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

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/mcL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

“It’s meaningless to just go by some recommendation covering time since the last treatment,” study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor at Uppsala University, both in Sweden, told this news organization.

“It’s misleading and potentially harmful for patients,” Dr. Burman said.

The findings were published online  in JAMA Network Open.
 

Finding the cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/mcL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs. 2.1; P = .002).
 

Close monitoring needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/mcL, versus 51/mcL for the remainder of the cohort (P < .001).

A cutoff value of 40/mcL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible – but that they should hold off on receiving a booster until their B-cell counts reach 40/mcL.

Regarding when a clinician should re-vaccinate, “the results from our study strongly suggest that you should not do that right away or just follow some generic guideline,” Dr. Burman said.

“You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/mcL” he added.

Dr. Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.
 

Too soon for B-cell measures?

Commenting for this news organization, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the United States for treating MS.

“Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines,” said Dr. Fox, who was not involved with the research.

“Given the unknown efficacy of these extended intervals, I don’t think we’re at the point of making management recommendations based upon B-cell counts,” he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Dr. Burman reported.

“Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class,” Dr. Fox said.

“Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data,” he noted.

“At this point, we don’t know which decisions were right or wrong, but I certainly don’t think we should judge clinicians for making decisions the best they could.”

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Dr. Burman reported no relevant financial relationships. Dr. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

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

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/mcL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

“It’s meaningless to just go by some recommendation covering time since the last treatment,” study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor at Uppsala University, both in Sweden, told this news organization.

“It’s misleading and potentially harmful for patients,” Dr. Burman said.

The findings were published online  in JAMA Network Open.
 

Finding the cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/mcL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs. 2.1; P = .002).
 

Close monitoring needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/mcL, versus 51/mcL for the remainder of the cohort (P < .001).

A cutoff value of 40/mcL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible – but that they should hold off on receiving a booster until their B-cell counts reach 40/mcL.

Regarding when a clinician should re-vaccinate, “the results from our study strongly suggest that you should not do that right away or just follow some generic guideline,” Dr. Burman said.

“You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/mcL” he added.

Dr. Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.
 

Too soon for B-cell measures?

Commenting for this news organization, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the United States for treating MS.

“Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines,” said Dr. Fox, who was not involved with the research.

“Given the unknown efficacy of these extended intervals, I don’t think we’re at the point of making management recommendations based upon B-cell counts,” he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Dr. Burman reported.

“Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class,” Dr. Fox said.

“Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data,” he noted.

“At this point, we don’t know which decisions were right or wrong, but I certainly don’t think we should judge clinicians for making decisions the best they could.”

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Dr. Burman reported no relevant financial relationships. Dr. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

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

Trauma surgeons are in the tough position of seeing victims just after gun violence across the United States, and they have some advice.

Their strategies can work regardless of where you stand on the Second Amendment of the Constitution, said Patricia Turner, MD. “Our proposals are embraced by both gun owners and non–gun owners alike, and we are unique in that regard.”

These “implementable solutions” could prevent the next massacre, Dr. Turner, executive director of the American College of Surgeons, said during a news briefing the group sponsored on June 2.

“Our future – indeed all of our futures – depend on our ability to find durable, actionable steps that we can implement tomorrow to save lives,” she said.
 

Firsthand perspective

“Sadly I’m here today as a trauma surgeon who has cared for two of the largest mass shootings in modern U.S. history,” said Ronald Stewart, MD, chair of the department of surgery at University Hospital in San Antonio, Texas.

Dr. Stewart treated victims of the 2017 Sutherland Springs First Baptist Church shooting – where 27 people died, including the shooter – and the recent Uvalde school shooting, both in Texas.

“The injuries inflicted by high-velocity weapons used at both of these attacks are horrific. A high-capacity, magazine-fed automatic rifle such as the AR-15 causes extremely destructive tissue wounds,” he said.

One of the group’s proposals is to increase the regulation of high-velocity weapons, including AR-15s.

“These wounds are horribly lethal at close range, and sadly, most victims do not survive long enough to make it to a trauma center,” Dr. Stewart said.

On a positive note, “all of our current [Uvalde] patients are improving, which really brings us joy in this dark time,” he said. “But all of them have a long road to deal with recovery with both the physical and emotional impact of their injuries.”

Jeffrey Kerby, MD, agreed.

“Trauma surgeons see the short-term physical effects of these injuries and watch patients struggle with the long-term impact of these wounds,” said Dr. Kerby, director of trauma and acute care surgery at the University of Alabama at Birmingham.
 

Surgeons feel ‘profound impact’ of shootings

“Firearm violence has a profound impact on surgeons, and we are the undisputed subject matter experts in treating the tragic results,” said Patrick Bailey, MD, medical director for advocacy at the American College of Surgeons.

“This impacts surgeons as well,” said Dr. Kerby, chair of the Committee on Trauma for the surgeons’ group. “We are human, and we can’t help but share in the grief, the pain, and the suffering that our patients endure.

“As a pediatric surgeon ... I have too often witnessed the impact of firearm violence, and obviously, the devastation extends beyond the victims to their families,” he said. “To put it succinctly, in our culture, parents are not supposed to be put in a position of burying their children.”
 

A public health crisis

“It’s important to recognize that we’ve been talking about a public health approach,” said Eileen Bulger, MD, acting chief of the trauma division at the University of Washington in Seattle. That strategy is important for engaging both firearm owners and communities that have a higher risk for firearm violence, she said.

A committee of the American College of Surgeons developed specific recommendations in 2018, which are still valid today. The group brought together surgeons from across the U.S. including “passionate firearm owners and experts in firearm safety,” Dr. Bulger said.

The committee, for example, agreed on 10 specific recommendations “that we believe are bipartisan and could have an immediate impact in saving lives.”

“I’m a lifelong gun owner,” Dr. Bailey said, emphasizing that the team’s process included participation and perspective from other surgeons “who, like me, are also gun owners, but gun owners who also seek to reduce the impact of firearm violence in our country.”

The recommendations address these areas:

• Gun ownership
• Firearm registration
• Licensure
• Education and training
• Ownership responsibilities
• Mandatory reporting and risk reduction
• Safety innovation and technology
• Research
• The culture of violence
• Social isolation and mental health

For example, “we currently have certain classes of weapons with significant offensive capability,” Dr. Bulger said, “that are appropriately restricted and regulated under the National Firearms Act as Class 3 weapons.”

This group includes fully automatic machine guns, explosive devices, and short-barrel shotguns.

“We recommend a formal reassessment of the firearms designated within each of these national firearms classifications,” Dr. Bulger said.

For example, high-capacity, magazine-fed semiautomatic rifles, such as the AR-15, should be considered for reclassification as NFA Class 3 firearms, or they should get a new designation with tighter regulation.

The ACS endorses formal firearm safety training for all new gun owners. Also, owners who do not provide reasonably safe firearm storage should be held responsible for events related to the discharge of their firearms, Dr. Bulger said. And people who are deemed an imminent threat to themselves or others through firearm ownership should be temporarily or permanently restricted, with due process.
 

Research and reporting reforms

The ACS is also calling for research on firearm injuries and firearm injury prevention to be federally funded, Dr. Bulger said. The research should be done in a nonpartisan manner, she said.

“We have concerns that the manner and tone in which information is released to the public may lead to copycat mass killers,” she said. “The ACS recommends that law enforcement officials and the press take steps to eliminate the notoriety of the shooter, for example.”

Dr. Bulger also addressed the mental health angle. “We encourage recognition of mental health warning signs and social isolation by teachers, counselors, peers, and parents.” When identified, immediate referral to professionals is needed.

In addition to these recommendations, another team from the American College of Surgeons has published an overview of ways to address the inequities that contribute to violence. “We advocate for federal funding to support the development of hospital-based and community programs for violence intervention and prevention,” Dr. Bulger said.

Dr. Bailey said that as a gun owner himself, he thinks other gun owners would support these recommendations.

“I do not believe that the steps recommended ... pose undue burden on the rights of individual gun owners,” he said.
 

The time is now

Most firearm injuries are not from mass shooting events, Dr. Kerby said.

“My own trauma center has seen a 40% increase in the number of firearm injuries just in the last 2 years,” he added, “and these numbers continue to grow.”

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

Trauma surgeons are in the tough position of seeing victims just after gun violence across the United States, and they have some advice.

Their strategies can work regardless of where you stand on the Second Amendment of the Constitution, said Patricia Turner, MD. “Our proposals are embraced by both gun owners and non–gun owners alike, and we are unique in that regard.”

These “implementable solutions” could prevent the next massacre, Dr. Turner, executive director of the American College of Surgeons, said during a news briefing the group sponsored on June 2.

“Our future – indeed all of our futures – depend on our ability to find durable, actionable steps that we can implement tomorrow to save lives,” she said.
 

Firsthand perspective

“Sadly I’m here today as a trauma surgeon who has cared for two of the largest mass shootings in modern U.S. history,” said Ronald Stewart, MD, chair of the department of surgery at University Hospital in San Antonio, Texas.

Dr. Stewart treated victims of the 2017 Sutherland Springs First Baptist Church shooting – where 27 people died, including the shooter – and the recent Uvalde school shooting, both in Texas.

“The injuries inflicted by high-velocity weapons used at both of these attacks are horrific. A high-capacity, magazine-fed automatic rifle such as the AR-15 causes extremely destructive tissue wounds,” he said.

One of the group’s proposals is to increase the regulation of high-velocity weapons, including AR-15s.

“These wounds are horribly lethal at close range, and sadly, most victims do not survive long enough to make it to a trauma center,” Dr. Stewart said.

On a positive note, “all of our current [Uvalde] patients are improving, which really brings us joy in this dark time,” he said. “But all of them have a long road to deal with recovery with both the physical and emotional impact of their injuries.”

Jeffrey Kerby, MD, agreed.

“Trauma surgeons see the short-term physical effects of these injuries and watch patients struggle with the long-term impact of these wounds,” said Dr. Kerby, director of trauma and acute care surgery at the University of Alabama at Birmingham.
 

Surgeons feel ‘profound impact’ of shootings

“Firearm violence has a profound impact on surgeons, and we are the undisputed subject matter experts in treating the tragic results,” said Patrick Bailey, MD, medical director for advocacy at the American College of Surgeons.

“This impacts surgeons as well,” said Dr. Kerby, chair of the Committee on Trauma for the surgeons’ group. “We are human, and we can’t help but share in the grief, the pain, and the suffering that our patients endure.

“As a pediatric surgeon ... I have too often witnessed the impact of firearm violence, and obviously, the devastation extends beyond the victims to their families,” he said. “To put it succinctly, in our culture, parents are not supposed to be put in a position of burying their children.”
 

A public health crisis

“It’s important to recognize that we’ve been talking about a public health approach,” said Eileen Bulger, MD, acting chief of the trauma division at the University of Washington in Seattle. That strategy is important for engaging both firearm owners and communities that have a higher risk for firearm violence, she said.

A committee of the American College of Surgeons developed specific recommendations in 2018, which are still valid today. The group brought together surgeons from across the U.S. including “passionate firearm owners and experts in firearm safety,” Dr. Bulger said.

The committee, for example, agreed on 10 specific recommendations “that we believe are bipartisan and could have an immediate impact in saving lives.”

“I’m a lifelong gun owner,” Dr. Bailey said, emphasizing that the team’s process included participation and perspective from other surgeons “who, like me, are also gun owners, but gun owners who also seek to reduce the impact of firearm violence in our country.”

The recommendations address these areas:

• Gun ownership
• Firearm registration
• Licensure
• Education and training
• Ownership responsibilities
• Mandatory reporting and risk reduction
• Safety innovation and technology
• Research
• The culture of violence
• Social isolation and mental health

For example, “we currently have certain classes of weapons with significant offensive capability,” Dr. Bulger said, “that are appropriately restricted and regulated under the National Firearms Act as Class 3 weapons.”

This group includes fully automatic machine guns, explosive devices, and short-barrel shotguns.

“We recommend a formal reassessment of the firearms designated within each of these national firearms classifications,” Dr. Bulger said.

For example, high-capacity, magazine-fed semiautomatic rifles, such as the AR-15, should be considered for reclassification as NFA Class 3 firearms, or they should get a new designation with tighter regulation.

The ACS endorses formal firearm safety training for all new gun owners. Also, owners who do not provide reasonably safe firearm storage should be held responsible for events related to the discharge of their firearms, Dr. Bulger said. And people who are deemed an imminent threat to themselves or others through firearm ownership should be temporarily or permanently restricted, with due process.
 

Research and reporting reforms

The ACS is also calling for research on firearm injuries and firearm injury prevention to be federally funded, Dr. Bulger said. The research should be done in a nonpartisan manner, she said.

“We have concerns that the manner and tone in which information is released to the public may lead to copycat mass killers,” she said. “The ACS recommends that law enforcement officials and the press take steps to eliminate the notoriety of the shooter, for example.”

Dr. Bulger also addressed the mental health angle. “We encourage recognition of mental health warning signs and social isolation by teachers, counselors, peers, and parents.” When identified, immediate referral to professionals is needed.

In addition to these recommendations, another team from the American College of Surgeons has published an overview of ways to address the inequities that contribute to violence. “We advocate for federal funding to support the development of hospital-based and community programs for violence intervention and prevention,” Dr. Bulger said.

Dr. Bailey said that as a gun owner himself, he thinks other gun owners would support these recommendations.

“I do not believe that the steps recommended ... pose undue burden on the rights of individual gun owners,” he said.
 

The time is now

Most firearm injuries are not from mass shooting events, Dr. Kerby said.

“My own trauma center has seen a 40% increase in the number of firearm injuries just in the last 2 years,” he added, “and these numbers continue to grow.”

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

Trauma surgeons are in the tough position of seeing victims just after gun violence across the United States, and they have some advice.

Their strategies can work regardless of where you stand on the Second Amendment of the Constitution, said Patricia Turner, MD. “Our proposals are embraced by both gun owners and non–gun owners alike, and we are unique in that regard.”

These “implementable solutions” could prevent the next massacre, Dr. Turner, executive director of the American College of Surgeons, said during a news briefing the group sponsored on June 2.

“Our future – indeed all of our futures – depend on our ability to find durable, actionable steps that we can implement tomorrow to save lives,” she said.
 

Firsthand perspective

“Sadly I’m here today as a trauma surgeon who has cared for two of the largest mass shootings in modern U.S. history,” said Ronald Stewart, MD, chair of the department of surgery at University Hospital in San Antonio, Texas.

Dr. Stewart treated victims of the 2017 Sutherland Springs First Baptist Church shooting – where 27 people died, including the shooter – and the recent Uvalde school shooting, both in Texas.

“The injuries inflicted by high-velocity weapons used at both of these attacks are horrific. A high-capacity, magazine-fed automatic rifle such as the AR-15 causes extremely destructive tissue wounds,” he said.

One of the group’s proposals is to increase the regulation of high-velocity weapons, including AR-15s.

“These wounds are horribly lethal at close range, and sadly, most victims do not survive long enough to make it to a trauma center,” Dr. Stewart said.

On a positive note, “all of our current [Uvalde] patients are improving, which really brings us joy in this dark time,” he said. “But all of them have a long road to deal with recovery with both the physical and emotional impact of their injuries.”

Jeffrey Kerby, MD, agreed.

“Trauma surgeons see the short-term physical effects of these injuries and watch patients struggle with the long-term impact of these wounds,” said Dr. Kerby, director of trauma and acute care surgery at the University of Alabama at Birmingham.
 

Surgeons feel ‘profound impact’ of shootings

“Firearm violence has a profound impact on surgeons, and we are the undisputed subject matter experts in treating the tragic results,” said Patrick Bailey, MD, medical director for advocacy at the American College of Surgeons.

“This impacts surgeons as well,” said Dr. Kerby, chair of the Committee on Trauma for the surgeons’ group. “We are human, and we can’t help but share in the grief, the pain, and the suffering that our patients endure.

“As a pediatric surgeon ... I have too often witnessed the impact of firearm violence, and obviously, the devastation extends beyond the victims to their families,” he said. “To put it succinctly, in our culture, parents are not supposed to be put in a position of burying their children.”
 

A public health crisis

“It’s important to recognize that we’ve been talking about a public health approach,” said Eileen Bulger, MD, acting chief of the trauma division at the University of Washington in Seattle. That strategy is important for engaging both firearm owners and communities that have a higher risk for firearm violence, she said.

A committee of the American College of Surgeons developed specific recommendations in 2018, which are still valid today. The group brought together surgeons from across the U.S. including “passionate firearm owners and experts in firearm safety,” Dr. Bulger said.

The committee, for example, agreed on 10 specific recommendations “that we believe are bipartisan and could have an immediate impact in saving lives.”

“I’m a lifelong gun owner,” Dr. Bailey said, emphasizing that the team’s process included participation and perspective from other surgeons “who, like me, are also gun owners, but gun owners who also seek to reduce the impact of firearm violence in our country.”

The recommendations address these areas:

• Gun ownership
• Firearm registration
• Licensure
• Education and training
• Ownership responsibilities
• Mandatory reporting and risk reduction
• Safety innovation and technology
• Research
• The culture of violence
• Social isolation and mental health

For example, “we currently have certain classes of weapons with significant offensive capability,” Dr. Bulger said, “that are appropriately restricted and regulated under the National Firearms Act as Class 3 weapons.”

This group includes fully automatic machine guns, explosive devices, and short-barrel shotguns.

“We recommend a formal reassessment of the firearms designated within each of these national firearms classifications,” Dr. Bulger said.

For example, high-capacity, magazine-fed semiautomatic rifles, such as the AR-15, should be considered for reclassification as NFA Class 3 firearms, or they should get a new designation with tighter regulation.

The ACS endorses formal firearm safety training for all new gun owners. Also, owners who do not provide reasonably safe firearm storage should be held responsible for events related to the discharge of their firearms, Dr. Bulger said. And people who are deemed an imminent threat to themselves or others through firearm ownership should be temporarily or permanently restricted, with due process.
 

Research and reporting reforms

The ACS is also calling for research on firearm injuries and firearm injury prevention to be federally funded, Dr. Bulger said. The research should be done in a nonpartisan manner, she said.

“We have concerns that the manner and tone in which information is released to the public may lead to copycat mass killers,” she said. “The ACS recommends that law enforcement officials and the press take steps to eliminate the notoriety of the shooter, for example.”

Dr. Bulger also addressed the mental health angle. “We encourage recognition of mental health warning signs and social isolation by teachers, counselors, peers, and parents.” When identified, immediate referral to professionals is needed.

In addition to these recommendations, another team from the American College of Surgeons has published an overview of ways to address the inequities that contribute to violence. “We advocate for federal funding to support the development of hospital-based and community programs for violence intervention and prevention,” Dr. Bulger said.

Dr. Bailey said that as a gun owner himself, he thinks other gun owners would support these recommendations.

“I do not believe that the steps recommended ... pose undue burden on the rights of individual gun owners,” he said.
 

The time is now

Most firearm injuries are not from mass shooting events, Dr. Kerby said.

“My own trauma center has seen a 40% increase in the number of firearm injuries just in the last 2 years,” he added, “and these numbers continue to grow.”

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

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

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

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

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

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