Study Overview

Objective. To examine whether discontinuation of nonsteroidal anti-inflammatory drug (NSAID) therapy and initiation of telephone-based cognitive behavioral therapy (CBT) is not worse than continuation of NSAIDs in the management of arthritis pain.

Design. Randomized controlled trial with noninferiority design.

Setting and participants. This study was a multicenter trial conducted across 4 Veterans Affairs health care systems in Boston, Providence, Connecticut, and North Florida/South Georgia that started September 2013 and ended September 2018. Eligibility criteria included being age 20 years or older, radiographic evidence of knee osteoarthritis, and use of an NSAID for knee pain on most days of the month for at least the past 3 months. Exclusion criteria included significant hearing impairments that may impede the conduct of the trial, current opioid prescriptions excluding tramadol, contraindications to NSAID use, recent or scheduled intra-articular injections or surgery, comorbid conditions other than knee pain that limited walking, and bilateral knee replacements or pain only in the replaced knee. Concurrent use of tramadol and other non-NSAID analgesics was permitted.

A total of 490 participants took part in the 2-week run-in period where their NSAID regimen was discontinued and they were started on a standardized dose of the NSAID meloxicam 15 mg daily. During the run-in period, 126 participants were excluded for several reasons, including worsening pain and patient withdrawal, yielding 364 participants who were randomized to continue meloxicam treatment or placebo for 4 weeks with blinding.

Intervention. Subsequent to the 4-week phase 1 placebo controlled trial, participants in the placebo group were given CBT via telephone (unblinded) for 10 weeks, and the meloxicam group continued treatment with meloxicam for phase 2. The CBT group received 10 modules over 10 weeks in 30- to 45-minute telephone contacts with a psychologist using a treatment manual modified for knee osteoarthritis. These modules consisted of 1 introductory module, 8 pain coping skills modules (eg, deep breathing and visual imagery, progressive muscle relaxation, physical activity and bodily mechanics, identifying unhealthy thoughts, balancing unhealthy thoughts, managing stress, time-based pacing, and sleep hygiene), and a final module emphasizing skill consolidation and relapse prevention. Outcomes were assessed at the end of the phase 1 and phase 2 periods.

Main outcome measures. Main study outcome measures included pain as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 4 weeks. Secondary outcomes included the WOMAC pain score, disability score, and global impression of change after treatment at 14 weeks. The WOMAC pain scale ranges from 0 to 20, and consists of 5 questions regarding severity of pain during walking, stair use, lying in bed at night, sitting, and standing, with 0 indicating no pain; 1, mild pain; 2, moderate pain; 3, severe pain; and 4, very severe pain for each item. The WOMAC disability scale measures self-reported difficulty in performing tasks that reflect lower-extremity physical function, including climbing stairs, rising from a chair, walking, and other activities of daily living. The global impression of change after treatment was measured on a 5-point scale (where 1 indicates much better and 5 indicates much worse). The minimum clinically important difference of the WOMAC pain scale is 2, based on prior literature. With the noninferiority design, the margin was set as a score of 1.

Main results. The placebo group consisted of 180 participants, with an average age of 58.2 years (SD, 11.8 years); 89% of them were male. The meloxicam group consisted of 184 participants, with an average age of 58.6 years (SD, 10 years); 84% of them were male. The average body mass index was 33.9 and 33.4 in each group, respectively. For the primary outcome, the placebo group had a worse pain score than the meloxicam group at 4 weeks (difference of 1.4; 95% confidence interval, 0.8- 2.0). At 14 weeks, the placebo group (with CBT) had a worse pain score than the meloxicam group (difference of 0.8; 95% CI, 0.2-1.4). There was no statistically significant difference in the disability score or global impression of change after treatment score between the 2 groups. The observed difference in pain score did not, however, exceed the minimum clinically important difference.

Conclusion. Placebo treatment and CBT are inferior to NSAIDs in managing pain for patients with knee osteoarthritis. The difference in pain may not be clinically important, and there were no differences in function at 14 weeks.

Commentary

Osteoarthritis is a common chronic condition that causes pain and disability and is often treated with oral analgesics. NSAIDs, despite few high-quality trials demonstrating their efficacy, are among the most commonly used treatment for osteoarthritis pain.¹ NSAID therapy, however, does have potential side effects, such as gastric reflux and renal dysfunction.² This withdrawal trial with placebo control contributes further evidence of the effectiveness of NSAIDs on knee osteoarthritis, demonstrating that indeed NSAIDs improve pain scores to a greater degree than placebo treatment. Augmenting placebo treatment with nonpharmacologic CBT was inferior to NSAIDs in pain management. The authors pointed out that the difference in pain score may not be clinically important, and that lower-extremity function was not different between the groups, concluding that, despite the higher pain score, CBT could be a treatment option, particularly for those who may have difficulty tolerating NSAID treatment.

The study population had a number of chronic conditions in addition to having knee arthritis, and thus likely were taking multiple medications for chronic disease management. Use of multiple medications is associated with an increased risk of rug interactions and adverse effects of medications.³ Thus, this attempt to assess whether a nonpharmacologic alternative treatment is noninferior to a drug treatment is a step toward building the evidence base for deprescribing and enhancing medication safety.⁴ Previous studies have examined other nonpharmacologic treatments for knee arthritis, such as acupuncture,⁵ and it is worthwhile to consider combining nonpharmacological approaches as an alternative to oral analgesic medication use.

Applications for Clinical Practice

This study advances our understanding of the effect of NSAID use on knee osteoarthritis when compared to placebo with CBT. Although this is a negative study that failed to show that placebo combined with CBT is noninferior to NSAIDs, it did quantify the expected treatment effect of NSAIDs and showed that this effect likely is not clinically important and/or does not alter lower-extremity function. Further studies are needed to identify other nonpharmacologic approaches and test whether combinations of approaches are effective in the management of chronic pain from osteoarthritis.

–William W. Hung, MD, MPH

Study Overview

Objective. To examine whether discontinuation of nonsteroidal anti-inflammatory drug (NSAID) therapy and initiation of telephone-based cognitive behavioral therapy (CBT) is not worse than continuation of NSAIDs in the management of arthritis pain.

Design. Randomized controlled trial with noninferiority design.

Setting and participants. This study was a multicenter trial conducted across 4 Veterans Affairs health care systems in Boston, Providence, Connecticut, and North Florida/South Georgia that started September 2013 and ended September 2018. Eligibility criteria included being age 20 years or older, radiographic evidence of knee osteoarthritis, and use of an NSAID for knee pain on most days of the month for at least the past 3 months. Exclusion criteria included significant hearing impairments that may impede the conduct of the trial, current opioid prescriptions excluding tramadol, contraindications to NSAID use, recent or scheduled intra-articular injections or surgery, comorbid conditions other than knee pain that limited walking, and bilateral knee replacements or pain only in the replaced knee. Concurrent use of tramadol and other non-NSAID analgesics was permitted.

A total of 490 participants took part in the 2-week run-in period where their NSAID regimen was discontinued and they were started on a standardized dose of the NSAID meloxicam 15 mg daily. During the run-in period, 126 participants were excluded for several reasons, including worsening pain and patient withdrawal, yielding 364 participants who were randomized to continue meloxicam treatment or placebo for 4 weeks with blinding.

Intervention. Subsequent to the 4-week phase 1 placebo controlled trial, participants in the placebo group were given CBT via telephone (unblinded) for 10 weeks, and the meloxicam group continued treatment with meloxicam for phase 2. The CBT group received 10 modules over 10 weeks in 30- to 45-minute telephone contacts with a psychologist using a treatment manual modified for knee osteoarthritis. These modules consisted of 1 introductory module, 8 pain coping skills modules (eg, deep breathing and visual imagery, progressive muscle relaxation, physical activity and bodily mechanics, identifying unhealthy thoughts, balancing unhealthy thoughts, managing stress, time-based pacing, and sleep hygiene), and a final module emphasizing skill consolidation and relapse prevention. Outcomes were assessed at the end of the phase 1 and phase 2 periods.

Main outcome measures. Main study outcome measures included pain as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 4 weeks. Secondary outcomes included the WOMAC pain score, disability score, and global impression of change after treatment at 14 weeks. The WOMAC pain scale ranges from 0 to 20, and consists of 5 questions regarding severity of pain during walking, stair use, lying in bed at night, sitting, and standing, with 0 indicating no pain; 1, mild pain; 2, moderate pain; 3, severe pain; and 4, very severe pain for each item. The WOMAC disability scale measures self-reported difficulty in performing tasks that reflect lower-extremity physical function, including climbing stairs, rising from a chair, walking, and other activities of daily living. The global impression of change after treatment was measured on a 5-point scale (where 1 indicates much better and 5 indicates much worse). The minimum clinically important difference of the WOMAC pain scale is 2, based on prior literature. With the noninferiority design, the margin was set as a score of 1.

Main results. The placebo group consisted of 180 participants, with an average age of 58.2 years (SD, 11.8 years); 89% of them were male. The meloxicam group consisted of 184 participants, with an average age of 58.6 years (SD, 10 years); 84% of them were male. The average body mass index was 33.9 and 33.4 in each group, respectively. For the primary outcome, the placebo group had a worse pain score than the meloxicam group at 4 weeks (difference of 1.4; 95% confidence interval, 0.8- 2.0). At 14 weeks, the placebo group (with CBT) had a worse pain score than the meloxicam group (difference of 0.8; 95% CI, 0.2-1.4). There was no statistically significant difference in the disability score or global impression of change after treatment score between the 2 groups. The observed difference in pain score did not, however, exceed the minimum clinically important difference.

Conclusion. Placebo treatment and CBT are inferior to NSAIDs in managing pain for patients with knee osteoarthritis. The difference in pain may not be clinically important, and there were no differences in function at 14 weeks.

Commentary

Osteoarthritis is a common chronic condition that causes pain and disability and is often treated with oral analgesics. NSAIDs, despite few high-quality trials demonstrating their efficacy, are among the most commonly used treatment for osteoarthritis pain.¹ NSAID therapy, however, does have potential side effects, such as gastric reflux and renal dysfunction.² This withdrawal trial with placebo control contributes further evidence of the effectiveness of NSAIDs on knee osteoarthritis, demonstrating that indeed NSAIDs improve pain scores to a greater degree than placebo treatment. Augmenting placebo treatment with nonpharmacologic CBT was inferior to NSAIDs in pain management. The authors pointed out that the difference in pain score may not be clinically important, and that lower-extremity function was not different between the groups, concluding that, despite the higher pain score, CBT could be a treatment option, particularly for those who may have difficulty tolerating NSAID treatment.

The study population had a number of chronic conditions in addition to having knee arthritis, and thus likely were taking multiple medications for chronic disease management. Use of multiple medications is associated with an increased risk of rug interactions and adverse effects of medications.³ Thus, this attempt to assess whether a nonpharmacologic alternative treatment is noninferior to a drug treatment is a step toward building the evidence base for deprescribing and enhancing medication safety.⁴ Previous studies have examined other nonpharmacologic treatments for knee arthritis, such as acupuncture,⁵ and it is worthwhile to consider combining nonpharmacological approaches as an alternative to oral analgesic medication use.

Applications for Clinical Practice

This study advances our understanding of the effect of NSAID use on knee osteoarthritis when compared to placebo with CBT. Although this is a negative study that failed to show that placebo combined with CBT is noninferior to NSAIDs, it did quantify the expected treatment effect of NSAIDs and showed that this effect likely is not clinically important and/or does not alter lower-extremity function. Further studies are needed to identify other nonpharmacologic approaches and test whether combinations of approaches are effective in the management of chronic pain from osteoarthritis.

–William W. Hung, MD, MPH

Study Overview

Objective. To examine whether discontinuation of nonsteroidal anti-inflammatory drug (NSAID) therapy and initiation of telephone-based cognitive behavioral therapy (CBT) is not worse than continuation of NSAIDs in the management of arthritis pain.

Design. Randomized controlled trial with noninferiority design.

Setting and participants. This study was a multicenter trial conducted across 4 Veterans Affairs health care systems in Boston, Providence, Connecticut, and North Florida/South Georgia that started September 2013 and ended September 2018. Eligibility criteria included being age 20 years or older, radiographic evidence of knee osteoarthritis, and use of an NSAID for knee pain on most days of the month for at least the past 3 months. Exclusion criteria included significant hearing impairments that may impede the conduct of the trial, current opioid prescriptions excluding tramadol, contraindications to NSAID use, recent or scheduled intra-articular injections or surgery, comorbid conditions other than knee pain that limited walking, and bilateral knee replacements or pain only in the replaced knee. Concurrent use of tramadol and other non-NSAID analgesics was permitted.

A total of 490 participants took part in the 2-week run-in period where their NSAID regimen was discontinued and they were started on a standardized dose of the NSAID meloxicam 15 mg daily. During the run-in period, 126 participants were excluded for several reasons, including worsening pain and patient withdrawal, yielding 364 participants who were randomized to continue meloxicam treatment or placebo for 4 weeks with blinding.

Intervention. Subsequent to the 4-week phase 1 placebo controlled trial, participants in the placebo group were given CBT via telephone (unblinded) for 10 weeks, and the meloxicam group continued treatment with meloxicam for phase 2. The CBT group received 10 modules over 10 weeks in 30- to 45-minute telephone contacts with a psychologist using a treatment manual modified for knee osteoarthritis. These modules consisted of 1 introductory module, 8 pain coping skills modules (eg, deep breathing and visual imagery, progressive muscle relaxation, physical activity and bodily mechanics, identifying unhealthy thoughts, balancing unhealthy thoughts, managing stress, time-based pacing, and sleep hygiene), and a final module emphasizing skill consolidation and relapse prevention. Outcomes were assessed at the end of the phase 1 and phase 2 periods.

Main outcome measures. Main study outcome measures included pain as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 4 weeks. Secondary outcomes included the WOMAC pain score, disability score, and global impression of change after treatment at 14 weeks. The WOMAC pain scale ranges from 0 to 20, and consists of 5 questions regarding severity of pain during walking, stair use, lying in bed at night, sitting, and standing, with 0 indicating no pain; 1, mild pain; 2, moderate pain; 3, severe pain; and 4, very severe pain for each item. The WOMAC disability scale measures self-reported difficulty in performing tasks that reflect lower-extremity physical function, including climbing stairs, rising from a chair, walking, and other activities of daily living. The global impression of change after treatment was measured on a 5-point scale (where 1 indicates much better and 5 indicates much worse). The minimum clinically important difference of the WOMAC pain scale is 2, based on prior literature. With the noninferiority design, the margin was set as a score of 1.

Main results. The placebo group consisted of 180 participants, with an average age of 58.2 years (SD, 11.8 years); 89% of them were male. The meloxicam group consisted of 184 participants, with an average age of 58.6 years (SD, 10 years); 84% of them were male. The average body mass index was 33.9 and 33.4 in each group, respectively. For the primary outcome, the placebo group had a worse pain score than the meloxicam group at 4 weeks (difference of 1.4; 95% confidence interval, 0.8- 2.0). At 14 weeks, the placebo group (with CBT) had a worse pain score than the meloxicam group (difference of 0.8; 95% CI, 0.2-1.4). There was no statistically significant difference in the disability score or global impression of change after treatment score between the 2 groups. The observed difference in pain score did not, however, exceed the minimum clinically important difference.

Conclusion. Placebo treatment and CBT are inferior to NSAIDs in managing pain for patients with knee osteoarthritis. The difference in pain may not be clinically important, and there were no differences in function at 14 weeks.

Commentary

Osteoarthritis is a common chronic condition that causes pain and disability and is often treated with oral analgesics. NSAIDs, despite few high-quality trials demonstrating their efficacy, are among the most commonly used treatment for osteoarthritis pain.¹ NSAID therapy, however, does have potential side effects, such as gastric reflux and renal dysfunction.² This withdrawal trial with placebo control contributes further evidence of the effectiveness of NSAIDs on knee osteoarthritis, demonstrating that indeed NSAIDs improve pain scores to a greater degree than placebo treatment. Augmenting placebo treatment with nonpharmacologic CBT was inferior to NSAIDs in pain management. The authors pointed out that the difference in pain score may not be clinically important, and that lower-extremity function was not different between the groups, concluding that, despite the higher pain score, CBT could be a treatment option, particularly for those who may have difficulty tolerating NSAID treatment.

The study population had a number of chronic conditions in addition to having knee arthritis, and thus likely were taking multiple medications for chronic disease management. Use of multiple medications is associated with an increased risk of rug interactions and adverse effects of medications.³ Thus, this attempt to assess whether a nonpharmacologic alternative treatment is noninferior to a drug treatment is a step toward building the evidence base for deprescribing and enhancing medication safety.⁴ Previous studies have examined other nonpharmacologic treatments for knee arthritis, such as acupuncture,⁵ and it is worthwhile to consider combining nonpharmacological approaches as an alternative to oral analgesic medication use.

Applications for Clinical Practice

This study advances our understanding of the effect of NSAID use on knee osteoarthritis when compared to placebo with CBT. Although this is a negative study that failed to show that placebo combined with CBT is noninferior to NSAIDs, it did quantify the expected treatment effect of NSAIDs and showed that this effect likely is not clinically important and/or does not alter lower-extremity function. Further studies are needed to identify other nonpharmacologic approaches and test whether combinations of approaches are effective in the management of chronic pain from osteoarthritis.

–William W. Hung, MD, MPH

A novel lower-cost noninvasive continuous glucose monitor (CGM) combined with a digital education/guidance program is set to launch in the United States and Europe this month for use in type 2 diabetes.

With the goal of improving management, or even reversing the condition, Neumara’s SugarBEAT device is thought to be the world’s first noninvasive CGM.

Its cost is anticipated to be far lower than traditional CGM, and it’s aimed at a different patient population: those with type 2 diabetes or prediabetes who may or may not be performing fingerstick glucose monitoring, but if they are, they still aren’t using the information to guide management.

“This isn’t about handing out devices and letting patients get on about it on their own accord. This is really about supporting those individuals,” Faz Chowdhury, MD, Nemaura’s chief executive officer, said in an interview.

He pointed to studies showing improvements in glycemic control in patients with type 2 diabetes who were instructed to perform fingerstick blood glucose testing seven times a day for 3-4 days a month and given advice about how to respond to the data.

“This is well established. We’re saying we can make that process a lot more scalable and affordable and convenient for the patient. ... The behavior change side is digitized,” Dr. Chowdhury said. “We want to provide a program to help people reverse their diabetes or at least stabilize it as much as possible.”

Nicholas Argento, MD, diabetes technology director at Maryland Endocrine and Diabetes, Columbia, said in an interview: “It’s interesting. They’re taking a very different approach. I think there’s a lot of validity to what they’re looking at because we have great CGMs right now, but because of the price point it’s not accessible to a lot of people.

“I think they’re onto something that could prove to be useful to a larger group of patients,” he added.
 

Worn a few days per month and accurate despite being noninvasive

Instead of inserting a catheter under the skin with a needle, as do current CGMs, the device comprises a small rechargeable transmitter and adhesive patch with a sensor that sits on the top of the skin, typically the upper arm. Glucose molecules are drawn out of the interstitial fluid just below the skin and into a chamber where the transmitter measures the glucose level and transmits the data every 5 minutes via Bluetooth to a smartphone app.

Despite this noninvasive approach, the device appears to be about as accurate as traditional CGMs, with comparable mean absolute relative difference (MARD) from a gold standard glucose measure of about 11%-12% with once-daily calibration versus 10%-11% for the Abbott FreeStyle Libre.

Unlike traditional CGMs, SugarBEAT is meant to be worn for only 14 hours at a time during the day and for 2-4 days per month rather than every day.

It’s not aimed at patients with type 1 diabetes or those with type 2 diabetes who are at high risk for hypoglycemia. It requires once-daily fingerstick calibration and is not indicated to replace fingersticks for treatment decisions.

SugarBEAT received a CE Mark in Europe as a Class IIb medical device in May 2019. That version provides real-time glucose values visible to the wearer. In the United States the company submitted a premarketing approval application for the device to the Food and Drug Administration in July 2020, which awaits a decision.

However, FDA is allowing it to enter the U.S. market as a “wellness” device that won’t deliver real-time values for now but instead will generate retroactive reports available to the physician and the patient.   

And last month, U.K.-based Neumara launched the BEATdiabetes site, which allows users to sign in and link to the device once it becomes available.

The site provides “scientifically validated, personalized coaching” based on a program developed at the Joslin Diabetes Clinic in Syracuse, N.Y., and will ultimately include monitoring of other cardiovascular risk factors with digital connectivity to a variety of wearables.
 

Fingerstick monitoring in type 2 diabetes is only so useful

“Fingerstick monitoring for type 2 diabetes is only so useful,” Dr. Argento said in an interview.

“It’s difficult to get people to monitor in a meaningful way.” If patients perform them only in the morning or at other sporadic times of the day, he said, “Then you get a one-dimensional picture ... and they don’t know what to do with the information anyway, so they stop doing it.”

In contrast, with SugarBEAT and BEATDiabetes, “I think it does address a need that fingerstick monitoring doesn’t.”

Dr. Argento did express a few caveats about the device, however. For one, it still requires one fingerstick a day for calibration. “If people don’t like needles, that might be a disincentive.”

Also, despite the apparently comparable mean absolute relative difference with that of conventional CGMs, that measure can still “hide” values that may be consistently either above or below target range.

“MARD is like A1c in that it’s useful but limited. ... It doesn’t tell you about variability or systemic bias,” he said.

Dr. Argento also said that he’d like to see data on the lag time between the interstitial fluid and blood glucose measures with this noninvasive method as compared with that of a subcutaneous catheter.

However, he acknowledged that these potentials for error would be less important for patients with type 2 diabetes who aren’t generally taking medications that increase their risk for hypoglycemia.

In all, he said, “stay tuned. I think this is part of a movement going away from point-in-time to looking at trends and wearables and data to enrich decision-making…There are still some unanswered questions I have but I think they’re onto a concept that’s useful for a broader population.”  

Dr. Chowdhury is an employee of Neumara. Dr. Argento consults for Senseonics and Dexcom, and is also a speaker for Dexcom.

This article first appeared on Medscape.com.

A novel lower-cost noninvasive continuous glucose monitor (CGM) combined with a digital education/guidance program is set to launch in the United States and Europe this month for use in type 2 diabetes.

With the goal of improving management, or even reversing the condition, Neumara’s SugarBEAT device is thought to be the world’s first noninvasive CGM.

Its cost is anticipated to be far lower than traditional CGM, and it’s aimed at a different patient population: those with type 2 diabetes or prediabetes who may or may not be performing fingerstick glucose monitoring, but if they are, they still aren’t using the information to guide management.

“This isn’t about handing out devices and letting patients get on about it on their own accord. This is really about supporting those individuals,” Faz Chowdhury, MD, Nemaura’s chief executive officer, said in an interview.

He pointed to studies showing improvements in glycemic control in patients with type 2 diabetes who were instructed to perform fingerstick blood glucose testing seven times a day for 3-4 days a month and given advice about how to respond to the data.

“This is well established. We’re saying we can make that process a lot more scalable and affordable and convenient for the patient. ... The behavior change side is digitized,” Dr. Chowdhury said. “We want to provide a program to help people reverse their diabetes or at least stabilize it as much as possible.”

Nicholas Argento, MD, diabetes technology director at Maryland Endocrine and Diabetes, Columbia, said in an interview: “It’s interesting. They’re taking a very different approach. I think there’s a lot of validity to what they’re looking at because we have great CGMs right now, but because of the price point it’s not accessible to a lot of people.

“I think they’re onto something that could prove to be useful to a larger group of patients,” he added.
 

Worn a few days per month and accurate despite being noninvasive

Instead of inserting a catheter under the skin with a needle, as do current CGMs, the device comprises a small rechargeable transmitter and adhesive patch with a sensor that sits on the top of the skin, typically the upper arm. Glucose molecules are drawn out of the interstitial fluid just below the skin and into a chamber where the transmitter measures the glucose level and transmits the data every 5 minutes via Bluetooth to a smartphone app.

Despite this noninvasive approach, the device appears to be about as accurate as traditional CGMs, with comparable mean absolute relative difference (MARD) from a gold standard glucose measure of about 11%-12% with once-daily calibration versus 10%-11% for the Abbott FreeStyle Libre.

Unlike traditional CGMs, SugarBEAT is meant to be worn for only 14 hours at a time during the day and for 2-4 days per month rather than every day.

It’s not aimed at patients with type 1 diabetes or those with type 2 diabetes who are at high risk for hypoglycemia. It requires once-daily fingerstick calibration and is not indicated to replace fingersticks for treatment decisions.

SugarBEAT received a CE Mark in Europe as a Class IIb medical device in May 2019. That version provides real-time glucose values visible to the wearer. In the United States the company submitted a premarketing approval application for the device to the Food and Drug Administration in July 2020, which awaits a decision.

However, FDA is allowing it to enter the U.S. market as a “wellness” device that won’t deliver real-time values for now but instead will generate retroactive reports available to the physician and the patient.   

And last month, U.K.-based Neumara launched the BEATdiabetes site, which allows users to sign in and link to the device once it becomes available.

The site provides “scientifically validated, personalized coaching” based on a program developed at the Joslin Diabetes Clinic in Syracuse, N.Y., and will ultimately include monitoring of other cardiovascular risk factors with digital connectivity to a variety of wearables.
 

Fingerstick monitoring in type 2 diabetes is only so useful

“Fingerstick monitoring for type 2 diabetes is only so useful,” Dr. Argento said in an interview.

“It’s difficult to get people to monitor in a meaningful way.” If patients perform them only in the morning or at other sporadic times of the day, he said, “Then you get a one-dimensional picture ... and they don’t know what to do with the information anyway, so they stop doing it.”

In contrast, with SugarBEAT and BEATDiabetes, “I think it does address a need that fingerstick monitoring doesn’t.”

Dr. Argento did express a few caveats about the device, however. For one, it still requires one fingerstick a day for calibration. “If people don’t like needles, that might be a disincentive.”

Also, despite the apparently comparable mean absolute relative difference with that of conventional CGMs, that measure can still “hide” values that may be consistently either above or below target range.

“MARD is like A1c in that it’s useful but limited. ... It doesn’t tell you about variability or systemic bias,” he said.

Dr. Argento also said that he’d like to see data on the lag time between the interstitial fluid and blood glucose measures with this noninvasive method as compared with that of a subcutaneous catheter.

However, he acknowledged that these potentials for error would be less important for patients with type 2 diabetes who aren’t generally taking medications that increase their risk for hypoglycemia.

In all, he said, “stay tuned. I think this is part of a movement going away from point-in-time to looking at trends and wearables and data to enrich decision-making…There are still some unanswered questions I have but I think they’re onto a concept that’s useful for a broader population.”  

Dr. Chowdhury is an employee of Neumara. Dr. Argento consults for Senseonics and Dexcom, and is also a speaker for Dexcom.

This article first appeared on Medscape.com.

A novel lower-cost noninvasive continuous glucose monitor (CGM) combined with a digital education/guidance program is set to launch in the United States and Europe this month for use in type 2 diabetes.

With the goal of improving management, or even reversing the condition, Neumara’s SugarBEAT device is thought to be the world’s first noninvasive CGM.

Its cost is anticipated to be far lower than traditional CGM, and it’s aimed at a different patient population: those with type 2 diabetes or prediabetes who may or may not be performing fingerstick glucose monitoring, but if they are, they still aren’t using the information to guide management.

“This isn’t about handing out devices and letting patients get on about it on their own accord. This is really about supporting those individuals,” Faz Chowdhury, MD, Nemaura’s chief executive officer, said in an interview.

He pointed to studies showing improvements in glycemic control in patients with type 2 diabetes who were instructed to perform fingerstick blood glucose testing seven times a day for 3-4 days a month and given advice about how to respond to the data.

“This is well established. We’re saying we can make that process a lot more scalable and affordable and convenient for the patient. ... The behavior change side is digitized,” Dr. Chowdhury said. “We want to provide a program to help people reverse their diabetes or at least stabilize it as much as possible.”

Nicholas Argento, MD, diabetes technology director at Maryland Endocrine and Diabetes, Columbia, said in an interview: “It’s interesting. They’re taking a very different approach. I think there’s a lot of validity to what they’re looking at because we have great CGMs right now, but because of the price point it’s not accessible to a lot of people.

“I think they’re onto something that could prove to be useful to a larger group of patients,” he added.
 

Worn a few days per month and accurate despite being noninvasive

Instead of inserting a catheter under the skin with a needle, as do current CGMs, the device comprises a small rechargeable transmitter and adhesive patch with a sensor that sits on the top of the skin, typically the upper arm. Glucose molecules are drawn out of the interstitial fluid just below the skin and into a chamber where the transmitter measures the glucose level and transmits the data every 5 minutes via Bluetooth to a smartphone app.

Despite this noninvasive approach, the device appears to be about as accurate as traditional CGMs, with comparable mean absolute relative difference (MARD) from a gold standard glucose measure of about 11%-12% with once-daily calibration versus 10%-11% for the Abbott FreeStyle Libre.

Unlike traditional CGMs, SugarBEAT is meant to be worn for only 14 hours at a time during the day and for 2-4 days per month rather than every day.

It’s not aimed at patients with type 1 diabetes or those with type 2 diabetes who are at high risk for hypoglycemia. It requires once-daily fingerstick calibration and is not indicated to replace fingersticks for treatment decisions.

SugarBEAT received a CE Mark in Europe as a Class IIb medical device in May 2019. That version provides real-time glucose values visible to the wearer. In the United States the company submitted a premarketing approval application for the device to the Food and Drug Administration in July 2020, which awaits a decision.

However, FDA is allowing it to enter the U.S. market as a “wellness” device that won’t deliver real-time values for now but instead will generate retroactive reports available to the physician and the patient.   

And last month, U.K.-based Neumara launched the BEATdiabetes site, which allows users to sign in and link to the device once it becomes available.

The site provides “scientifically validated, personalized coaching” based on a program developed at the Joslin Diabetes Clinic in Syracuse, N.Y., and will ultimately include monitoring of other cardiovascular risk factors with digital connectivity to a variety of wearables.
 

Fingerstick monitoring in type 2 diabetes is only so useful

“Fingerstick monitoring for type 2 diabetes is only so useful,” Dr. Argento said in an interview.

“It’s difficult to get people to monitor in a meaningful way.” If patients perform them only in the morning or at other sporadic times of the day, he said, “Then you get a one-dimensional picture ... and they don’t know what to do with the information anyway, so they stop doing it.”

In contrast, with SugarBEAT and BEATDiabetes, “I think it does address a need that fingerstick monitoring doesn’t.”

Dr. Argento did express a few caveats about the device, however. For one, it still requires one fingerstick a day for calibration. “If people don’t like needles, that might be a disincentive.”

Also, despite the apparently comparable mean absolute relative difference with that of conventional CGMs, that measure can still “hide” values that may be consistently either above or below target range.

“MARD is like A1c in that it’s useful but limited. ... It doesn’t tell you about variability or systemic bias,” he said.

Dr. Argento also said that he’d like to see data on the lag time between the interstitial fluid and blood glucose measures with this noninvasive method as compared with that of a subcutaneous catheter.

However, he acknowledged that these potentials for error would be less important for patients with type 2 diabetes who aren’t generally taking medications that increase their risk for hypoglycemia.

In all, he said, “stay tuned. I think this is part of a movement going away from point-in-time to looking at trends and wearables and data to enrich decision-making…There are still some unanswered questions I have but I think they’re onto a concept that’s useful for a broader population.”  

Dr. Chowdhury is an employee of Neumara. Dr. Argento consults for Senseonics and Dexcom, and is also a speaker for Dexcom.

This article first appeared on Medscape.com.

Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.

“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.

“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.

The statement was published online Nov. 30 in Circulation.
 

Evolution in knowledge

During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.

“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.

“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.

The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.

Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.

Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.

Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.

Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
 

Lifestyle interventions

The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.

Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.

Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.

“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.

There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.

The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.

They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.

The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.

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

Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.

“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.

“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.

The statement was published online Nov. 30 in Circulation.
 

Evolution in knowledge

During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.

“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.

“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.

The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.

Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.

Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.

Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.

Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
 

Lifestyle interventions

The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.

Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.

Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.

“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.

There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.

The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.

They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.

The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.

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

Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.

“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.

“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.

The statement was published online Nov. 30 in Circulation.
 

Evolution in knowledge

During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.

“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.

“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.

The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.

Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.

Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.

Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.

Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
 

Lifestyle interventions

The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.

Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.

Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.

“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.

There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.

The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.

They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.

The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.

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

Activated circulating basophils appear to play a key role in mediating the underappreciated phenomenon of acute-on-chronic itch flares in atopic dermatitis, Brian S. Kim, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Recent years have brought enormous progress in understanding how chronic itch in patients with atopic dermatitis (AD) is mediated by type 2 cytokines, including interleukin-13, IL-4, and IL-31, as well as by Janus kinase (JAK) signaling. This has led to development of potent therapies targeting these mediators, including dupilumab (Dupixent) and the investigational agents tralokinumab, lebrikizumab, abrocitinib, upadacitinib, baricitinib, and the IL-31 inhibitor nemolizumab.

“This is now one of the most active areas in the field of dermatology,” observed Dr. Kim, a dermatologist and codirector of the Center for the Study of Itch and Sensory Disorders at Washington University in St. Louis.

He has figured prominently in this effort. He and his coinvestigators conducted translational studies in mouse models which unraveled key mechanisms by which the immune system responsible for skin inflammation in AD communicates with the nervous system to trigger the neural sensation of itch. He also led a phase 2 randomized trial in 307 patients with AD, which demonstrated that the investigational JAK1/JAK2 inhibitor ruxolitinib cream markedly improved itch within 36 hours, well before subsequent improvement in skin inflammation – and the topical JAK inhibitor did so with minimal systemic absorption.

Compared with chronic itch, much less research attention has been devoted to the phenomenon of acute itch flares superimposed upon the chronic itch of AD. These acute-on-chronic itch flares are a common feature of the disease. In a soon-to-be-published study of 159 AD patients in the placebo arm of a clinical trial, Dr. Kim and coinvestigators found that 26% exhibited a pattern of acute itch flares during the course of a single month. During the next month, 3.1% of patients under study went from an acute-on-chronic itch pattern in month 1 to a nonflare pattern, 20% went from a nonflare pattern in month 1 to acute itch flares in month 2, and 23% of the overall study population retained their pattern of acute itch flares through both months.

“This does not seem to be just a static phenotype, but rather these patients can evolve over time. And we think that this can be driven by allergen-specific IgE,” according to Dr. Kim.

Indeed, the investigators found that patients with allergen-specific IgE in their serum were roughly twice as likely to exhibit the acute-on-chronic itch flare pattern than those without allergen-specific IgE.

The classical thinking has been that IgE binds to its receptors on mast cells, causing mast cell degranulation and release of histamine and other itch-inducing molecules. Yet antihistamines have proven notoriously ineffective for the treatment of AD.

Circulating basophils capable of working their way into inflamed skin also have IgE receptors. Dr. Kim and colleagues have shown that allergen-specific IgE in mice binds to those receptors, causing the basophils to degenerate, releasing itch-promoting chemicals. They have subsequently carried over this work into the clinical arena.

“We’ve found that patients with atopic dermatitis have significantly higher expression of receptors for IgE in their basophils than in the basophils of healthy controls, indicating perhaps that the basophils in patients with atopic dermatitis are much more prone to stimulation by allergen by way of IgE. This is a new concept that we’re exploring,” Dr. Kim said.

“We haven’t really known before what IgE does in atopic dermatitis, but it turns out that it may actually play a very important role in triggering acute flares of itch,” the dermatologist explained. “What’s been surprising is that the IgE activity is not mediated so much by mast cells, which are tissue-resident; the predominant means appears to be that IgE acts on basophils. That then creates release not of histamine, but of leukotriene C4, which is a very potent pruritogen. This may be responsible for those acute itch flares.”

Asked during an audience Q&A how allergen-specific IgE–mediated basophil activation might be targeted therapeutically in order to prevent acute-on-chronic itch flares in patients with AD, Dr. Kim mentioned two possibilities. One is treatment with potent anti-IgE agents, which to date have not been adequately tested for their antipruritic prowess in AD.

“Also, there’s another molecule that seems to be relatively basophil-selective and -specific that’s just been discovered by my colleague Xinzhong Dong at Johns Hopkins University [in Baltimore] – called MRGPRX2 – that may actually be a potentially viable way to go after basophils, maybe even by depleting them if you had an antibody against that,” Dr. Kim said. He was a coinvestigator in Dr. Dong’s recent study characterizing MRGPRX2, the mast-cell-expressed Mas-related G-protein–coupled receptor activator.

Dr. Kim reported receiving research funding from Cara Therapeutics and LEO Pharma, holding a patent for the use of JAK inhibitors in chronic itch, and serving as a consultant to numerous pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Activated circulating basophils appear to play a key role in mediating the underappreciated phenomenon of acute-on-chronic itch flares in atopic dermatitis, Brian S. Kim, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Recent years have brought enormous progress in understanding how chronic itch in patients with atopic dermatitis (AD) is mediated by type 2 cytokines, including interleukin-13, IL-4, and IL-31, as well as by Janus kinase (JAK) signaling. This has led to development of potent therapies targeting these mediators, including dupilumab (Dupixent) and the investigational agents tralokinumab, lebrikizumab, abrocitinib, upadacitinib, baricitinib, and the IL-31 inhibitor nemolizumab.

“This is now one of the most active areas in the field of dermatology,” observed Dr. Kim, a dermatologist and codirector of the Center for the Study of Itch and Sensory Disorders at Washington University in St. Louis.

He has figured prominently in this effort. He and his coinvestigators conducted translational studies in mouse models which unraveled key mechanisms by which the immune system responsible for skin inflammation in AD communicates with the nervous system to trigger the neural sensation of itch. He also led a phase 2 randomized trial in 307 patients with AD, which demonstrated that the investigational JAK1/JAK2 inhibitor ruxolitinib cream markedly improved itch within 36 hours, well before subsequent improvement in skin inflammation – and the topical JAK inhibitor did so with minimal systemic absorption.

Compared with chronic itch, much less research attention has been devoted to the phenomenon of acute itch flares superimposed upon the chronic itch of AD. These acute-on-chronic itch flares are a common feature of the disease. In a soon-to-be-published study of 159 AD patients in the placebo arm of a clinical trial, Dr. Kim and coinvestigators found that 26% exhibited a pattern of acute itch flares during the course of a single month. During the next month, 3.1% of patients under study went from an acute-on-chronic itch pattern in month 1 to a nonflare pattern, 20% went from a nonflare pattern in month 1 to acute itch flares in month 2, and 23% of the overall study population retained their pattern of acute itch flares through both months.

“This does not seem to be just a static phenotype, but rather these patients can evolve over time. And we think that this can be driven by allergen-specific IgE,” according to Dr. Kim.

Indeed, the investigators found that patients with allergen-specific IgE in their serum were roughly twice as likely to exhibit the acute-on-chronic itch flare pattern than those without allergen-specific IgE.

The classical thinking has been that IgE binds to its receptors on mast cells, causing mast cell degranulation and release of histamine and other itch-inducing molecules. Yet antihistamines have proven notoriously ineffective for the treatment of AD.

Circulating basophils capable of working their way into inflamed skin also have IgE receptors. Dr. Kim and colleagues have shown that allergen-specific IgE in mice binds to those receptors, causing the basophils to degenerate, releasing itch-promoting chemicals. They have subsequently carried over this work into the clinical arena.

“We’ve found that patients with atopic dermatitis have significantly higher expression of receptors for IgE in their basophils than in the basophils of healthy controls, indicating perhaps that the basophils in patients with atopic dermatitis are much more prone to stimulation by allergen by way of IgE. This is a new concept that we’re exploring,” Dr. Kim said.

“We haven’t really known before what IgE does in atopic dermatitis, but it turns out that it may actually play a very important role in triggering acute flares of itch,” the dermatologist explained. “What’s been surprising is that the IgE activity is not mediated so much by mast cells, which are tissue-resident; the predominant means appears to be that IgE acts on basophils. That then creates release not of histamine, but of leukotriene C4, which is a very potent pruritogen. This may be responsible for those acute itch flares.”

Asked during an audience Q&A how allergen-specific IgE–mediated basophil activation might be targeted therapeutically in order to prevent acute-on-chronic itch flares in patients with AD, Dr. Kim mentioned two possibilities. One is treatment with potent anti-IgE agents, which to date have not been adequately tested for their antipruritic prowess in AD.

“Also, there’s another molecule that seems to be relatively basophil-selective and -specific that’s just been discovered by my colleague Xinzhong Dong at Johns Hopkins University [in Baltimore] – called MRGPRX2 – that may actually be a potentially viable way to go after basophils, maybe even by depleting them if you had an antibody against that,” Dr. Kim said. He was a coinvestigator in Dr. Dong’s recent study characterizing MRGPRX2, the mast-cell-expressed Mas-related G-protein–coupled receptor activator.

Dr. Kim reported receiving research funding from Cara Therapeutics and LEO Pharma, holding a patent for the use of JAK inhibitors in chronic itch, and serving as a consultant to numerous pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Activated circulating basophils appear to play a key role in mediating the underappreciated phenomenon of acute-on-chronic itch flares in atopic dermatitis, Brian S. Kim, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Recent years have brought enormous progress in understanding how chronic itch in patients with atopic dermatitis (AD) is mediated by type 2 cytokines, including interleukin-13, IL-4, and IL-31, as well as by Janus kinase (JAK) signaling. This has led to development of potent therapies targeting these mediators, including dupilumab (Dupixent) and the investigational agents tralokinumab, lebrikizumab, abrocitinib, upadacitinib, baricitinib, and the IL-31 inhibitor nemolizumab.

“This is now one of the most active areas in the field of dermatology,” observed Dr. Kim, a dermatologist and codirector of the Center for the Study of Itch and Sensory Disorders at Washington University in St. Louis.

He has figured prominently in this effort. He and his coinvestigators conducted translational studies in mouse models which unraveled key mechanisms by which the immune system responsible for skin inflammation in AD communicates with the nervous system to trigger the neural sensation of itch. He also led a phase 2 randomized trial in 307 patients with AD, which demonstrated that the investigational JAK1/JAK2 inhibitor ruxolitinib cream markedly improved itch within 36 hours, well before subsequent improvement in skin inflammation – and the topical JAK inhibitor did so with minimal systemic absorption.

Compared with chronic itch, much less research attention has been devoted to the phenomenon of acute itch flares superimposed upon the chronic itch of AD. These acute-on-chronic itch flares are a common feature of the disease. In a soon-to-be-published study of 159 AD patients in the placebo arm of a clinical trial, Dr. Kim and coinvestigators found that 26% exhibited a pattern of acute itch flares during the course of a single month. During the next month, 3.1% of patients under study went from an acute-on-chronic itch pattern in month 1 to a nonflare pattern, 20% went from a nonflare pattern in month 1 to acute itch flares in month 2, and 23% of the overall study population retained their pattern of acute itch flares through both months.

“This does not seem to be just a static phenotype, but rather these patients can evolve over time. And we think that this can be driven by allergen-specific IgE,” according to Dr. Kim.

Indeed, the investigators found that patients with allergen-specific IgE in their serum were roughly twice as likely to exhibit the acute-on-chronic itch flare pattern than those without allergen-specific IgE.

The classical thinking has been that IgE binds to its receptors on mast cells, causing mast cell degranulation and release of histamine and other itch-inducing molecules. Yet antihistamines have proven notoriously ineffective for the treatment of AD.

Circulating basophils capable of working their way into inflamed skin also have IgE receptors. Dr. Kim and colleagues have shown that allergen-specific IgE in mice binds to those receptors, causing the basophils to degenerate, releasing itch-promoting chemicals. They have subsequently carried over this work into the clinical arena.

“We’ve found that patients with atopic dermatitis have significantly higher expression of receptors for IgE in their basophils than in the basophils of healthy controls, indicating perhaps that the basophils in patients with atopic dermatitis are much more prone to stimulation by allergen by way of IgE. This is a new concept that we’re exploring,” Dr. Kim said.

“We haven’t really known before what IgE does in atopic dermatitis, but it turns out that it may actually play a very important role in triggering acute flares of itch,” the dermatologist explained. “What’s been surprising is that the IgE activity is not mediated so much by mast cells, which are tissue-resident; the predominant means appears to be that IgE acts on basophils. That then creates release not of histamine, but of leukotriene C4, which is a very potent pruritogen. This may be responsible for those acute itch flares.”

Asked during an audience Q&A how allergen-specific IgE–mediated basophil activation might be targeted therapeutically in order to prevent acute-on-chronic itch flares in patients with AD, Dr. Kim mentioned two possibilities. One is treatment with potent anti-IgE agents, which to date have not been adequately tested for their antipruritic prowess in AD.

“Also, there’s another molecule that seems to be relatively basophil-selective and -specific that’s just been discovered by my colleague Xinzhong Dong at Johns Hopkins University [in Baltimore] – called MRGPRX2 – that may actually be a potentially viable way to go after basophils, maybe even by depleting them if you had an antibody against that,” Dr. Kim said. He was a coinvestigator in Dr. Dong’s recent study characterizing MRGPRX2, the mast-cell-expressed Mas-related G-protein–coupled receptor activator.

Dr. Kim reported receiving research funding from Cara Therapeutics and LEO Pharma, holding a patent for the use of JAK inhibitors in chronic itch, and serving as a consultant to numerous pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.

Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.

For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.¹

An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.² A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
 

Riding the cytokine storm

Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.

Benefits and drawbacks of immunosuppressive agents

To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.

They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.³

SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.

From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.⁴ CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.

Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.

According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.⁵ As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.⁵ Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.


 

COVID-19 safety protocols for cannabis users

Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.

Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.

A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.⁶

Conclusion

The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.

COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
 

References

1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.

2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.

3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.

4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.

5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html

6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.

An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.

Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.

For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.¹

An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.² A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
 

Riding the cytokine storm

Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.

Benefits and drawbacks of immunosuppressive agents

To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.

They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.³

SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.

From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.⁴ CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.

Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.

According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.⁵ As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.⁵ Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.


 

COVID-19 safety protocols for cannabis users

Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.

Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.

A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.⁶

Conclusion

The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.

COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
 

References

1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.

2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.

3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.

4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.

5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html

6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.

An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.

Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.

For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.¹

An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.² A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
 

Riding the cytokine storm

Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.

Benefits and drawbacks of immunosuppressive agents

To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.

They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.³

SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.

From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.⁴ CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.

Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.

According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.⁵ As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.⁵ Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.


 

COVID-19 safety protocols for cannabis users

Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.

Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.

A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.⁶

Conclusion

The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.

COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
 

References

1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.

2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.

3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.

4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.

5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html

6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.

The dramatic advances in targeted therapies for late-stage melanoma capture the headlines, but a recent Australian study quietly concluded that the most cost-effective way to lower both the incidence of melanoma and deaths caused by the malignancy over the long haul is through primary prevention in the form of daily sunscreen use, according to Laura Korb Ferris, MD, PhD, a dermatologist and director of clinical trials in the department of dermatology at the University of Pittsburgh.

Wavebreakmedia Ltd/Thinkstock

“I think it’s really important that we recognize the importance of preventing skin cancer, and not just early detection, not just treatment of late disease,” Dr. Ferris said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

She highlighted the Australian cost-effectiveness analysis, which used Markov modeling of data from two published population-based, randomized controlled trials carried out in Queensland, Australia.

The cost-effectiveness study compared the estimated long-term impact of three different approaches to control of melanoma: a primary prevention strategy, which basically consisted of promoting daily sunscreen use and other forms of sun protection; early detection through annual whole-body skin examinations by physicians starting at age 50; and no intervention. The analysis provided estimates of the number of cases of melanoma, deaths caused by melanoma, nonmelanoma skin cancers, and quality of life outcomes over the course of 30 years starting in 50-year-old men and women.

Primary prevention through sun protection was the clear winner, as shown by the results:

• A 44% reduction in the incidence of melanoma, compared with early detection via annual physician skin examinations.
• A 39% reduction in projected melanoma deaths compared with early detection, which in turn achieved only a 2% reduction when compared with no intervention.
• 27% fewer keratinocyte cancers excised than with annual skin examinations.
• A 21.7% reduction in societal costs, compared with an early-detection program.

Daily sunscreen use for primary prevention was also associated with a modest 0.1% increase in quality-adjusted life-years. “Prevention is low cost, low risk, and effective,” Dr. Ferris observed.

The investigators noted that, while residents of the Australian state of Queensland are mainly fair-skinned and confront high UV radiation levels throughout the year, somewhat limiting the generalizability of the study findings, the relationships between the costs of interventional strategies and their outcomes should be proportional in other countries.

True enough, but a strategy of annual skin examinations starting at age 50 years as modeled in the Australian study is not the most productive way to conduct a melanoma early-detection program, Dr. Ferris said. She noted that data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program show that the median age at diagnosis of melanoma in the United States is 65 years, while the median age at death caused by the malignancy is 71 years. That information is helpful in formulating strategies to improve early detection through more focused, higher-yield screening.

UPMC

Case in point: European investigators have estimated that, by screening everyone age 50 years and older, 475 people need to be screened and an average of 19.6 lesions must be biopsied in order to detect one melanoma. But by reserving screening for those age 50 years and up who have any one of three risk factors – a personal history of melanoma, atypical nevi, or at least 40 common nevi – those numbers drop dramatically: 98 people need to be screened and 13.5 lesions biopsied to detect one melanoma. And by further narrowing the screened population to those age 65 years or older with any of the three risk factors, 63 seniors would need to be screened and 9.2 lesions excised to find one melanoma.

Total-body skin examinations are time-consuming for dermatologists. In a recent U.S. study, investigators determined that the additional face-to-face time required per skin cancer detected by doing a total-body skin exam in adults who present to a dermatologist for another reason is 4.5 hours. And that’s just the time involved in detecting any type of skin cancer.

“To get that number for melanoma, multiply by 15 to 20,” Dr. Ferris said.

The investigators also determined that, for each decade of advancing age and increment in lighter skin phototype, the number-needed-to-examine in order to identify one skin cancer of any type decreased.

“By focusing on patients who are older and have fair skin types we can get that time down to about 1 hour,” commented Dr. Ferris, who penned an editorial perspective on the study.

While many dermatologists recommend that people with a high common nevus count undergo frequent screening for melanoma because they are at particularly high risk for invasive disease, a couple of recent studies challenge that notion, she pointed out. One was a retrospective study of 326 consecutive new melanoma patients which found that patients with a higher nevus count had thinner melanomas and a greater likelihood of in situ melanoma. Patients who presented with invasive melanoma had a mean total nevus count of 31.5 lesions, while those with in situ melanoma averaged 57.2 nevi. Each additional nevus was associated with a 4% reduction in the likelihood of invasive melanoma, independent of age and sex.

The other study included 566 newly diagnosed melanoma patients in two U.S. centers. Among the 56% of patients who were younger than 60 years, those who had more than 50 total nevi were 68% less likely to have a thick melanoma in a logistic regression analysis that controlled for demographic factors, as well as anatomic location of the melanoma, histologic subtype, and skin cancer screening frequency. In contrast, younger patients with more than 5 atypical nevi were 2.43-fold more likely to have thicker melanomas than were those with no such lesions. The lesson, according to the investigators, is that total nevus count isn’t a reliable determinant of a patient’s risk status or the need for skin examinations.

Dr. Ferris reported no financial conflicts of interest regarding her presentation.

Global Academy for Medical Education and this news organization are owned by the same company.

[email protected]

The dramatic advances in targeted therapies for late-stage melanoma capture the headlines, but a recent Australian study quietly concluded that the most cost-effective way to lower both the incidence of melanoma and deaths caused by the malignancy over the long haul is through primary prevention in the form of daily sunscreen use, according to Laura Korb Ferris, MD, PhD, a dermatologist and director of clinical trials in the department of dermatology at the University of Pittsburgh.

Wavebreakmedia Ltd/Thinkstock

“I think it’s really important that we recognize the importance of preventing skin cancer, and not just early detection, not just treatment of late disease,” Dr. Ferris said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

She highlighted the Australian cost-effectiveness analysis, which used Markov modeling of data from two published population-based, randomized controlled trials carried out in Queensland, Australia.

The cost-effectiveness study compared the estimated long-term impact of three different approaches to control of melanoma: a primary prevention strategy, which basically consisted of promoting daily sunscreen use and other forms of sun protection; early detection through annual whole-body skin examinations by physicians starting at age 50; and no intervention. The analysis provided estimates of the number of cases of melanoma, deaths caused by melanoma, nonmelanoma skin cancers, and quality of life outcomes over the course of 30 years starting in 50-year-old men and women.

Primary prevention through sun protection was the clear winner, as shown by the results:

• A 44% reduction in the incidence of melanoma, compared with early detection via annual physician skin examinations.
• A 39% reduction in projected melanoma deaths compared with early detection, which in turn achieved only a 2% reduction when compared with no intervention.
• 27% fewer keratinocyte cancers excised than with annual skin examinations.
• A 21.7% reduction in societal costs, compared with an early-detection program.

Daily sunscreen use for primary prevention was also associated with a modest 0.1% increase in quality-adjusted life-years. “Prevention is low cost, low risk, and effective,” Dr. Ferris observed.

The investigators noted that, while residents of the Australian state of Queensland are mainly fair-skinned and confront high UV radiation levels throughout the year, somewhat limiting the generalizability of the study findings, the relationships between the costs of interventional strategies and their outcomes should be proportional in other countries.

True enough, but a strategy of annual skin examinations starting at age 50 years as modeled in the Australian study is not the most productive way to conduct a melanoma early-detection program, Dr. Ferris said. She noted that data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program show that the median age at diagnosis of melanoma in the United States is 65 years, while the median age at death caused by the malignancy is 71 years. That information is helpful in formulating strategies to improve early detection through more focused, higher-yield screening.

UPMC

Case in point: European investigators have estimated that, by screening everyone age 50 years and older, 475 people need to be screened and an average of 19.6 lesions must be biopsied in order to detect one melanoma. But by reserving screening for those age 50 years and up who have any one of three risk factors – a personal history of melanoma, atypical nevi, or at least 40 common nevi – those numbers drop dramatically: 98 people need to be screened and 13.5 lesions biopsied to detect one melanoma. And by further narrowing the screened population to those age 65 years or older with any of the three risk factors, 63 seniors would need to be screened and 9.2 lesions excised to find one melanoma.

Total-body skin examinations are time-consuming for dermatologists. In a recent U.S. study, investigators determined that the additional face-to-face time required per skin cancer detected by doing a total-body skin exam in adults who present to a dermatologist for another reason is 4.5 hours. And that’s just the time involved in detecting any type of skin cancer.

“To get that number for melanoma, multiply by 15 to 20,” Dr. Ferris said.

The investigators also determined that, for each decade of advancing age and increment in lighter skin phototype, the number-needed-to-examine in order to identify one skin cancer of any type decreased.

“By focusing on patients who are older and have fair skin types we can get that time down to about 1 hour,” commented Dr. Ferris, who penned an editorial perspective on the study.

While many dermatologists recommend that people with a high common nevus count undergo frequent screening for melanoma because they are at particularly high risk for invasive disease, a couple of recent studies challenge that notion, she pointed out. One was a retrospective study of 326 consecutive new melanoma patients which found that patients with a higher nevus count had thinner melanomas and a greater likelihood of in situ melanoma. Patients who presented with invasive melanoma had a mean total nevus count of 31.5 lesions, while those with in situ melanoma averaged 57.2 nevi. Each additional nevus was associated with a 4% reduction in the likelihood of invasive melanoma, independent of age and sex.

The other study included 566 newly diagnosed melanoma patients in two U.S. centers. Among the 56% of patients who were younger than 60 years, those who had more than 50 total nevi were 68% less likely to have a thick melanoma in a logistic regression analysis that controlled for demographic factors, as well as anatomic location of the melanoma, histologic subtype, and skin cancer screening frequency. In contrast, younger patients with more than 5 atypical nevi were 2.43-fold more likely to have thicker melanomas than were those with no such lesions. The lesson, according to the investigators, is that total nevus count isn’t a reliable determinant of a patient’s risk status or the need for skin examinations.

Dr. Ferris reported no financial conflicts of interest regarding her presentation.

Global Academy for Medical Education and this news organization are owned by the same company.

[email protected]

The dramatic advances in targeted therapies for late-stage melanoma capture the headlines, but a recent Australian study quietly concluded that the most cost-effective way to lower both the incidence of melanoma and deaths caused by the malignancy over the long haul is through primary prevention in the form of daily sunscreen use, according to Laura Korb Ferris, MD, PhD, a dermatologist and director of clinical trials in the department of dermatology at the University of Pittsburgh.

Wavebreakmedia Ltd/Thinkstock

“I think it’s really important that we recognize the importance of preventing skin cancer, and not just early detection, not just treatment of late disease,” Dr. Ferris said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

She highlighted the Australian cost-effectiveness analysis, which used Markov modeling of data from two published population-based, randomized controlled trials carried out in Queensland, Australia.

The cost-effectiveness study compared the estimated long-term impact of three different approaches to control of melanoma: a primary prevention strategy, which basically consisted of promoting daily sunscreen use and other forms of sun protection; early detection through annual whole-body skin examinations by physicians starting at age 50; and no intervention. The analysis provided estimates of the number of cases of melanoma, deaths caused by melanoma, nonmelanoma skin cancers, and quality of life outcomes over the course of 30 years starting in 50-year-old men and women.

Primary prevention through sun protection was the clear winner, as shown by the results:

• A 44% reduction in the incidence of melanoma, compared with early detection via annual physician skin examinations.
• A 39% reduction in projected melanoma deaths compared with early detection, which in turn achieved only a 2% reduction when compared with no intervention.
• 27% fewer keratinocyte cancers excised than with annual skin examinations.
• A 21.7% reduction in societal costs, compared with an early-detection program.

Daily sunscreen use for primary prevention was also associated with a modest 0.1% increase in quality-adjusted life-years. “Prevention is low cost, low risk, and effective,” Dr. Ferris observed.

The investigators noted that, while residents of the Australian state of Queensland are mainly fair-skinned and confront high UV radiation levels throughout the year, somewhat limiting the generalizability of the study findings, the relationships between the costs of interventional strategies and their outcomes should be proportional in other countries.

True enough, but a strategy of annual skin examinations starting at age 50 years as modeled in the Australian study is not the most productive way to conduct a melanoma early-detection program, Dr. Ferris said. She noted that data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program show that the median age at diagnosis of melanoma in the United States is 65 years, while the median age at death caused by the malignancy is 71 years. That information is helpful in formulating strategies to improve early detection through more focused, higher-yield screening.

UPMC

Case in point: European investigators have estimated that, by screening everyone age 50 years and older, 475 people need to be screened and an average of 19.6 lesions must be biopsied in order to detect one melanoma. But by reserving screening for those age 50 years and up who have any one of three risk factors – a personal history of melanoma, atypical nevi, or at least 40 common nevi – those numbers drop dramatically: 98 people need to be screened and 13.5 lesions biopsied to detect one melanoma. And by further narrowing the screened population to those age 65 years or older with any of the three risk factors, 63 seniors would need to be screened and 9.2 lesions excised to find one melanoma.

Total-body skin examinations are time-consuming for dermatologists. In a recent U.S. study, investigators determined that the additional face-to-face time required per skin cancer detected by doing a total-body skin exam in adults who present to a dermatologist for another reason is 4.5 hours. And that’s just the time involved in detecting any type of skin cancer.

“To get that number for melanoma, multiply by 15 to 20,” Dr. Ferris said.

The investigators also determined that, for each decade of advancing age and increment in lighter skin phototype, the number-needed-to-examine in order to identify one skin cancer of any type decreased.

“By focusing on patients who are older and have fair skin types we can get that time down to about 1 hour,” commented Dr. Ferris, who penned an editorial perspective on the study.

While many dermatologists recommend that people with a high common nevus count undergo frequent screening for melanoma because they are at particularly high risk for invasive disease, a couple of recent studies challenge that notion, she pointed out. One was a retrospective study of 326 consecutive new melanoma patients which found that patients with a higher nevus count had thinner melanomas and a greater likelihood of in situ melanoma. Patients who presented with invasive melanoma had a mean total nevus count of 31.5 lesions, while those with in situ melanoma averaged 57.2 nevi. Each additional nevus was associated with a 4% reduction in the likelihood of invasive melanoma, independent of age and sex.

The other study included 566 newly diagnosed melanoma patients in two U.S. centers. Among the 56% of patients who were younger than 60 years, those who had more than 50 total nevi were 68% less likely to have a thick melanoma in a logistic regression analysis that controlled for demographic factors, as well as anatomic location of the melanoma, histologic subtype, and skin cancer screening frequency. In contrast, younger patients with more than 5 atypical nevi were 2.43-fold more likely to have thicker melanomas than were those with no such lesions. The lesson, according to the investigators, is that total nevus count isn’t a reliable determinant of a patient’s risk status or the need for skin examinations.

Dr. Ferris reported no financial conflicts of interest regarding her presentation.

Global Academy for Medical Education and this news organization are owned by the same company.

[email protected]

Low-dose chest CT for lung cancer screening provides the opportunity to simultaneously screen patients for osteoporosis, detecting notably higher rates of osteoporosis in men than the traditional tool of DXA, research published in the Journal of Bone and Mineral Research shows.

“Our large-scale, multicenter study of bone density measured from routine low-dose CT scans demonstrated the great potential of using low-dose CT for the opportunistic screening of osteoporosis as an alternative to standard DXA scans,” said senior author Wei Tian, MD, of the Chinese Academy of Engineering and Peking University, in a press statement from the journal.

“Our study revealed the unexpectedly high prevalence of osteoporosis in men, which may impact on the management strategy of men in the future,” Dr. Tian added.

Josephine Therkildsen, MD, of Herning Hospital, Denmark, who has conducted similar research using cardiac CT scans, said the findings add important new insights into the issue of opportunistic screening.

“The results are highly interesting, as they show that low-dose CT-based opportunistic screening could identify a substantial number of patients with low lumbar bone mineral density (BMD) with the future potential to diagnose osteoporosis and initiate relevant treatment before a fracture occurs,” she told this news organization.

Perry J. Pickhardt, MD, chief of gastrointestinal imaging at the University of Wisconsin School of Medicine and Public Health in Madison, agrees. He said in an interview that CT scans of the chest and abdomen, commonly performed for a variety of clinical indications and widespread in most developed countries, can in fact be essential for the detection of a multitude of other concerns – yet are underused for those other purposes.

Use of CT in this way “would likely be very cost effective and clinically efficacious,” he said, adding: “We are seeing greatly increased interest in leveraging this extra information that is contained within every CT scan.” And, “Importantly, artificial intelligence advances now allow for automated approaches, which should allow for expanded use.”
 

Lung cancer CT scans shed light on osteoporosis prevalence

In the study, led by Xiaoguang Cheng, MD, PhD, of the department of radiology, Beijing Jishuitan Hospital, China, researchers examined lung cancer CT screening data from the prospective China Biobank Project to determine the prevalence of osteoporosis in China.

This included the thoracic low-dose CT scans of 69,095 adults, including 40,733 men and 28,362 women, taken between 2018 and 2019.

To screen for osteoporosis, they used quantitative CT software to evaluate lumbar spine (L1-L2) trabecular volume BMD (vBMD) and diagnostic criteria from the American College of Radiology. Using the vBMD measures from the CT imaging, they found the prevalence of osteoporosis among those over 50 years of age in the Chinese population to be 29% for women (49 million) and 13.5% for men (22.8 million).

Interestingly, the osteoporosis prevalence rate among women was comparable to estimates in the population derived from DXA (29.1%); however, the rate in men was twice that estimated from DXA scans (6.5%).

Decreases in trabecular vBMD with age were observed in both genders. However, declines were steeper among women, who had higher peak trabecular vBMD (185.4 mg/cm³), compared with men (176.6 mg/cm³) at age 30-34 years, but significantly lower measures (62.4 mg/cm³) than men (92.1 mg/cm³) at age 80 years.

The prevalence of osteoporosis in women increased from 2.8% at age 50-54 years to 79.8% at age 85 or older, while in men, the prevalence was 3.2% at age 50-54 years and 44.1% at age 85 or older.

“This is the first study to establish Chinese reference data for vBMD using opportunistic screening from low-dose chest CT in a large population cohort,” the authors write.

“The opportunistic screening of osteoporosis using low-dose CT is clinically feasible and requires no additional exposure to ionizing radiation.”

In addition, no additional equipment or patient time was required, suggesting that “this approach has potential for opportunistic screening for osteoporosis.”

They note, however, that further cohort studies are needed to assess clinical utility of this method.
 

CT ‘likely a more accurate measure’ of volumetric BMD

Dr. Pickhardt said the differences in osteoporosis prevalence observed between DXA and CT-derived measures in men likely reflect the greater accuracy of CT.

“DXA is a planar technique with a number of drawbacks,” he said in an interview. “CT provides a more direct volumetric measure and is likely a more accurate method for BMD assessment.”

He speculated that the greater differences between DXA versus CT seen in men than women “may relate to sex differences in cortical bone of vertebral bodies, which cannot be separated from the underlying trabecular bone with DXA (whereas CT directly measures the inner trabecular bone).” 

The authors note that, although areal BMD (aBMD) derived from DXA is required for osteoporosis diagnosis according to World Health Organization criteria, “trabecular vBMD derived from CT can be also used for diagnosis based on thresholds published by the American College of Radiology of 120 mg/cm³ and 80 mg/cm³ to define osteopenia and osteoporosis, respectively, thresholds that were subsequently confirmed for the Chinese population.”

Furthermore, vBMD has been shown in some studies to be more strongly related to fracture risk, compared with DXA aBMD measures.

Importantly, in another recent study involving 9,223 adults, Dr. Pickhardt and colleagues reported that bone and muscle biomarkers derived from CT were comparable to the Fracture Risk Assessment Tool score for the presymptomatic prediction of future osteoporotic fractures.

Dr. Pickhardt is an advisor to Bracco Imaging and Zebra Medical Vision. Dr. Therkildsen has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Low-dose chest CT for lung cancer screening provides the opportunity to simultaneously screen patients for osteoporosis, detecting notably higher rates of osteoporosis in men than the traditional tool of DXA, research published in the Journal of Bone and Mineral Research shows.

“Our large-scale, multicenter study of bone density measured from routine low-dose CT scans demonstrated the great potential of using low-dose CT for the opportunistic screening of osteoporosis as an alternative to standard DXA scans,” said senior author Wei Tian, MD, of the Chinese Academy of Engineering and Peking University, in a press statement from the journal.

“Our study revealed the unexpectedly high prevalence of osteoporosis in men, which may impact on the management strategy of men in the future,” Dr. Tian added.

Josephine Therkildsen, MD, of Herning Hospital, Denmark, who has conducted similar research using cardiac CT scans, said the findings add important new insights into the issue of opportunistic screening.

“The results are highly interesting, as they show that low-dose CT-based opportunistic screening could identify a substantial number of patients with low lumbar bone mineral density (BMD) with the future potential to diagnose osteoporosis and initiate relevant treatment before a fracture occurs,” she told this news organization.

Perry J. Pickhardt, MD, chief of gastrointestinal imaging at the University of Wisconsin School of Medicine and Public Health in Madison, agrees. He said in an interview that CT scans of the chest and abdomen, commonly performed for a variety of clinical indications and widespread in most developed countries, can in fact be essential for the detection of a multitude of other concerns – yet are underused for those other purposes.

Use of CT in this way “would likely be very cost effective and clinically efficacious,” he said, adding: “We are seeing greatly increased interest in leveraging this extra information that is contained within every CT scan.” And, “Importantly, artificial intelligence advances now allow for automated approaches, which should allow for expanded use.”
 

Lung cancer CT scans shed light on osteoporosis prevalence

In the study, led by Xiaoguang Cheng, MD, PhD, of the department of radiology, Beijing Jishuitan Hospital, China, researchers examined lung cancer CT screening data from the prospective China Biobank Project to determine the prevalence of osteoporosis in China.

This included the thoracic low-dose CT scans of 69,095 adults, including 40,733 men and 28,362 women, taken between 2018 and 2019.

To screen for osteoporosis, they used quantitative CT software to evaluate lumbar spine (L1-L2) trabecular volume BMD (vBMD) and diagnostic criteria from the American College of Radiology. Using the vBMD measures from the CT imaging, they found the prevalence of osteoporosis among those over 50 years of age in the Chinese population to be 29% for women (49 million) and 13.5% for men (22.8 million).

Interestingly, the osteoporosis prevalence rate among women was comparable to estimates in the population derived from DXA (29.1%); however, the rate in men was twice that estimated from DXA scans (6.5%).

Decreases in trabecular vBMD with age were observed in both genders. However, declines were steeper among women, who had higher peak trabecular vBMD (185.4 mg/cm³), compared with men (176.6 mg/cm³) at age 30-34 years, but significantly lower measures (62.4 mg/cm³) than men (92.1 mg/cm³) at age 80 years.

The prevalence of osteoporosis in women increased from 2.8% at age 50-54 years to 79.8% at age 85 or older, while in men, the prevalence was 3.2% at age 50-54 years and 44.1% at age 85 or older.

“This is the first study to establish Chinese reference data for vBMD using opportunistic screening from low-dose chest CT in a large population cohort,” the authors write.

“The opportunistic screening of osteoporosis using low-dose CT is clinically feasible and requires no additional exposure to ionizing radiation.”

In addition, no additional equipment or patient time was required, suggesting that “this approach has potential for opportunistic screening for osteoporosis.”

They note, however, that further cohort studies are needed to assess clinical utility of this method.
 

CT ‘likely a more accurate measure’ of volumetric BMD

Dr. Pickhardt said the differences in osteoporosis prevalence observed between DXA and CT-derived measures in men likely reflect the greater accuracy of CT.

“DXA is a planar technique with a number of drawbacks,” he said in an interview. “CT provides a more direct volumetric measure and is likely a more accurate method for BMD assessment.”

He speculated that the greater differences between DXA versus CT seen in men than women “may relate to sex differences in cortical bone of vertebral bodies, which cannot be separated from the underlying trabecular bone with DXA (whereas CT directly measures the inner trabecular bone).” 

The authors note that, although areal BMD (aBMD) derived from DXA is required for osteoporosis diagnosis according to World Health Organization criteria, “trabecular vBMD derived from CT can be also used for diagnosis based on thresholds published by the American College of Radiology of 120 mg/cm³ and 80 mg/cm³ to define osteopenia and osteoporosis, respectively, thresholds that were subsequently confirmed for the Chinese population.”

Furthermore, vBMD has been shown in some studies to be more strongly related to fracture risk, compared with DXA aBMD measures.

Importantly, in another recent study involving 9,223 adults, Dr. Pickhardt and colleagues reported that bone and muscle biomarkers derived from CT were comparable to the Fracture Risk Assessment Tool score for the presymptomatic prediction of future osteoporotic fractures.

Dr. Pickhardt is an advisor to Bracco Imaging and Zebra Medical Vision. Dr. Therkildsen has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Low-dose chest CT for lung cancer screening provides the opportunity to simultaneously screen patients for osteoporosis, detecting notably higher rates of osteoporosis in men than the traditional tool of DXA, research published in the Journal of Bone and Mineral Research shows.

“Our large-scale, multicenter study of bone density measured from routine low-dose CT scans demonstrated the great potential of using low-dose CT for the opportunistic screening of osteoporosis as an alternative to standard DXA scans,” said senior author Wei Tian, MD, of the Chinese Academy of Engineering and Peking University, in a press statement from the journal.

“Our study revealed the unexpectedly high prevalence of osteoporosis in men, which may impact on the management strategy of men in the future,” Dr. Tian added.

Josephine Therkildsen, MD, of Herning Hospital, Denmark, who has conducted similar research using cardiac CT scans, said the findings add important new insights into the issue of opportunistic screening.

“The results are highly interesting, as they show that low-dose CT-based opportunistic screening could identify a substantial number of patients with low lumbar bone mineral density (BMD) with the future potential to diagnose osteoporosis and initiate relevant treatment before a fracture occurs,” she told this news organization.

Perry J. Pickhardt, MD, chief of gastrointestinal imaging at the University of Wisconsin School of Medicine and Public Health in Madison, agrees. He said in an interview that CT scans of the chest and abdomen, commonly performed for a variety of clinical indications and widespread in most developed countries, can in fact be essential for the detection of a multitude of other concerns – yet are underused for those other purposes.

Use of CT in this way “would likely be very cost effective and clinically efficacious,” he said, adding: “We are seeing greatly increased interest in leveraging this extra information that is contained within every CT scan.” And, “Importantly, artificial intelligence advances now allow for automated approaches, which should allow for expanded use.”
 

Lung cancer CT scans shed light on osteoporosis prevalence

In the study, led by Xiaoguang Cheng, MD, PhD, of the department of radiology, Beijing Jishuitan Hospital, China, researchers examined lung cancer CT screening data from the prospective China Biobank Project to determine the prevalence of osteoporosis in China.

This included the thoracic low-dose CT scans of 69,095 adults, including 40,733 men and 28,362 women, taken between 2018 and 2019.

To screen for osteoporosis, they used quantitative CT software to evaluate lumbar spine (L1-L2) trabecular volume BMD (vBMD) and diagnostic criteria from the American College of Radiology. Using the vBMD measures from the CT imaging, they found the prevalence of osteoporosis among those over 50 years of age in the Chinese population to be 29% for women (49 million) and 13.5% for men (22.8 million).

Interestingly, the osteoporosis prevalence rate among women was comparable to estimates in the population derived from DXA (29.1%); however, the rate in men was twice that estimated from DXA scans (6.5%).

Decreases in trabecular vBMD with age were observed in both genders. However, declines were steeper among women, who had higher peak trabecular vBMD (185.4 mg/cm³), compared with men (176.6 mg/cm³) at age 30-34 years, but significantly lower measures (62.4 mg/cm³) than men (92.1 mg/cm³) at age 80 years.

The prevalence of osteoporosis in women increased from 2.8% at age 50-54 years to 79.8% at age 85 or older, while in men, the prevalence was 3.2% at age 50-54 years and 44.1% at age 85 or older.

“This is the first study to establish Chinese reference data for vBMD using opportunistic screening from low-dose chest CT in a large population cohort,” the authors write.

“The opportunistic screening of osteoporosis using low-dose CT is clinically feasible and requires no additional exposure to ionizing radiation.”

In addition, no additional equipment or patient time was required, suggesting that “this approach has potential for opportunistic screening for osteoporosis.”

They note, however, that further cohort studies are needed to assess clinical utility of this method.
 

CT ‘likely a more accurate measure’ of volumetric BMD

Dr. Pickhardt said the differences in osteoporosis prevalence observed between DXA and CT-derived measures in men likely reflect the greater accuracy of CT.

“DXA is a planar technique with a number of drawbacks,” he said in an interview. “CT provides a more direct volumetric measure and is likely a more accurate method for BMD assessment.”

He speculated that the greater differences between DXA versus CT seen in men than women “may relate to sex differences in cortical bone of vertebral bodies, which cannot be separated from the underlying trabecular bone with DXA (whereas CT directly measures the inner trabecular bone).” 

The authors note that, although areal BMD (aBMD) derived from DXA is required for osteoporosis diagnosis according to World Health Organization criteria, “trabecular vBMD derived from CT can be also used for diagnosis based on thresholds published by the American College of Radiology of 120 mg/cm³ and 80 mg/cm³ to define osteopenia and osteoporosis, respectively, thresholds that were subsequently confirmed for the Chinese population.”

Furthermore, vBMD has been shown in some studies to be more strongly related to fracture risk, compared with DXA aBMD measures.

Importantly, in another recent study involving 9,223 adults, Dr. Pickhardt and colleagues reported that bone and muscle biomarkers derived from CT were comparable to the Fracture Risk Assessment Tool score for the presymptomatic prediction of future osteoporotic fractures.

Dr. Pickhardt is an advisor to Bracco Imaging and Zebra Medical Vision. Dr. Therkildsen has reported no relevant financial relationships.

This article first appeared on Medscape.com.

A radioactive diagnostic agent has been approved by the U.S. Food and Drug Administration for use in patients with prostate cancer, but only for those treated at two institutions in California.

The product, Gallium 68 PSMA-11 (Ga 68 PSMA-11), is the first agent approved specifically for use in positron-emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)–positive lesions in men with prostate cancer, the FDA noted.

This imaging approach can “detect whether or not the cancer has spread to other parts of the body,” commented Alex Gorovets, MD, acting deputy director of the Office of Specialty Medicine in the FDA’s Center for Drug Evaluation and Research.

Ga 68 PSMA-11 is indicated for use in patients with suspected prostate cancer metastasis whose conditions are potentially curable by surgery or radiotherapy and in patients with suspected prostate cancer recurrence, as determined on the basis of elevated serum prostate-specific antigen (PSA) levels.
 

Institutional use only

Ga 68 PSMA-11 has been approved for institutional use at the University of California, Los Angeles and the University of California, San Francisco under an academic new drug application (NDA).

The FDA approval was based partly on a clinical trial conducted by the UCSF and UCLA research teams on the effectiveness of PSMA-PET.

“It is rare for academic institutions to obtain FDA approval of a drug, and this unique collaboration has led to what is one of the first coapprovals of a drug at two institutions,” said Thomas Hope, MD, an associate professor at UCSF. “We hope that this first step will lead to a more widespread availability of this imaging test to men with prostate cancer throughout the country.”

Ga 68 PSMA-11 was developed outside the United States at the University of Heidelberg (Germany).

A commercial NDA from Telix Pharmaceuticals for TL591-CDx, a radiopharmaceutical cold kit for the preparation of Ga 68 PSMA-11 injection, is under consideration by the FDA.

The agency noted that two other PET diagnostic agents – fluciclovine F18 and choline C11 – are approved for prostate cancer imaging. However, they are only approved for use in patients with suspected cancer recurrence.
 

Trial results with PSMA-PET/CT

“PSMA-PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” commented T. Martin Ma, MD, PhD, of UCLA.

Dr. Ma presented a U.S. study on the technique at the recent annual meeting of the American Society for Radiation Oncology. That study showed that PSMA-PET/CT led to nodal upstaging in 19.7% of patients and metastasis upstaging in 9.4%.

He said these results were similar to those from the Australian proPSMA trial, which was published in The Lancet earlier this year. That trial found PSMA-PET/CT to be superior to conventional imaging with CT and bone scanning for primary staging of high-risk prostate cancer.

“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma commented.

“PSMA-PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Center, Melbourne, who was not involved in either study.

“PSMA-PET/CT has challenged conventional imaging in staging before curative-intent surgery or radiotherapy,” Dr. Eapen added.

The accuracy of PSMA-PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview last month. This superior accuracy can ultimately affect management. The imaging has additional benefits of lower radiation dose as well as reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.
 

Trial results with Ga 68 PSMA-11

The safety and efficacy of Ga 68 PSMA-11 were evaluated in two prospective clinical trials with a total of 960 men with prostate cancer, each of whom received one injection of the product.

The first trial involved 325 patients with biopsy-proven prostate cancer who underwent PET/CT or PET/MRI scans performed with Ga 68 PSMA-11.

“These patients were candidates for surgical removal of the prostate gland and pelvic lymph nodes and were considered at higher risk for metastasis. Among the patients who proceeded to surgery, those with positive readings in the pelvic lymph nodes on Ga 68 PSMA-11 PET had a clinically important rate of metastatic cancer confirmed by surgical pathology,” the FDA noted.

“The availability of this information prior to treatment is expected to have important implications for patient care,” the FDA commented. “For example, it may spare certain patients from undergoing unnecessary surgery.”

The second trial enrolled 635 patients with rising serum PSA levels after initial prostate surgery or radiotherapy. All patients received a single Ga 68 PSMA-11 PET/CT scan or PET/MRI scan.

About three-quarters of patients (74%) had at least one positive lesion detected by Ga 68 PSMA-11 PET in at least one region – bone, prostate bed, pelvic lymph node, or extra-pelvic soft tissue.

“In patients with positive Ga 68 PSMA-11 PET readings who had correlative tissue pathology from biopsies, results from baseline or follow-up imaging by conventional methods, and serial PSA levels available for comparison, local recurrence or metastasis of prostate cancer was confirmed in an estimated 91% of cases,” the FDA noted.

“Thus, the second trial demonstrated that Ga 68 PSMA-11 PET can detect sites of disease in patients with biochemical evidence of recurrent prostate cancer, thereby providing important information that may impact the approach to therapy,” the agency added.

The FDA also noted that no serious adverse reactions were attributed to Ga 68 PSMA-11. The most common adverse reactions were nausea, diarrhea, and dizziness.

The FDA said there is a risk for misdiagnosis because Ga 68 PSMA-11 binding may occur in other types of cancer, and certain nonmalignant processes may lead to errors in interpreting images. In addition, there are radiation risks because Ga 68 PSMA-11 contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk for cancer.

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

A radioactive diagnostic agent has been approved by the U.S. Food and Drug Administration for use in patients with prostate cancer, but only for those treated at two institutions in California.

The product, Gallium 68 PSMA-11 (Ga 68 PSMA-11), is the first agent approved specifically for use in positron-emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)–positive lesions in men with prostate cancer, the FDA noted.

This imaging approach can “detect whether or not the cancer has spread to other parts of the body,” commented Alex Gorovets, MD, acting deputy director of the Office of Specialty Medicine in the FDA’s Center for Drug Evaluation and Research.

Ga 68 PSMA-11 is indicated for use in patients with suspected prostate cancer metastasis whose conditions are potentially curable by surgery or radiotherapy and in patients with suspected prostate cancer recurrence, as determined on the basis of elevated serum prostate-specific antigen (PSA) levels.
 

Institutional use only

Ga 68 PSMA-11 has been approved for institutional use at the University of California, Los Angeles and the University of California, San Francisco under an academic new drug application (NDA).

The FDA approval was based partly on a clinical trial conducted by the UCSF and UCLA research teams on the effectiveness of PSMA-PET.

“It is rare for academic institutions to obtain FDA approval of a drug, and this unique collaboration has led to what is one of the first coapprovals of a drug at two institutions,” said Thomas Hope, MD, an associate professor at UCSF. “We hope that this first step will lead to a more widespread availability of this imaging test to men with prostate cancer throughout the country.”

Ga 68 PSMA-11 was developed outside the United States at the University of Heidelberg (Germany).

A commercial NDA from Telix Pharmaceuticals for TL591-CDx, a radiopharmaceutical cold kit for the preparation of Ga 68 PSMA-11 injection, is under consideration by the FDA.

The agency noted that two other PET diagnostic agents – fluciclovine F18 and choline C11 – are approved for prostate cancer imaging. However, they are only approved for use in patients with suspected cancer recurrence.
 

Trial results with PSMA-PET/CT

“PSMA-PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” commented T. Martin Ma, MD, PhD, of UCLA.

Dr. Ma presented a U.S. study on the technique at the recent annual meeting of the American Society for Radiation Oncology. That study showed that PSMA-PET/CT led to nodal upstaging in 19.7% of patients and metastasis upstaging in 9.4%.

He said these results were similar to those from the Australian proPSMA trial, which was published in The Lancet earlier this year. That trial found PSMA-PET/CT to be superior to conventional imaging with CT and bone scanning for primary staging of high-risk prostate cancer.

“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma commented.

“PSMA-PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Center, Melbourne, who was not involved in either study.

“PSMA-PET/CT has challenged conventional imaging in staging before curative-intent surgery or radiotherapy,” Dr. Eapen added.

The accuracy of PSMA-PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview last month. This superior accuracy can ultimately affect management. The imaging has additional benefits of lower radiation dose as well as reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.
 

Trial results with Ga 68 PSMA-11

The safety and efficacy of Ga 68 PSMA-11 were evaluated in two prospective clinical trials with a total of 960 men with prostate cancer, each of whom received one injection of the product.

The first trial involved 325 patients with biopsy-proven prostate cancer who underwent PET/CT or PET/MRI scans performed with Ga 68 PSMA-11.

“These patients were candidates for surgical removal of the prostate gland and pelvic lymph nodes and were considered at higher risk for metastasis. Among the patients who proceeded to surgery, those with positive readings in the pelvic lymph nodes on Ga 68 PSMA-11 PET had a clinically important rate of metastatic cancer confirmed by surgical pathology,” the FDA noted.

“The availability of this information prior to treatment is expected to have important implications for patient care,” the FDA commented. “For example, it may spare certain patients from undergoing unnecessary surgery.”

The second trial enrolled 635 patients with rising serum PSA levels after initial prostate surgery or radiotherapy. All patients received a single Ga 68 PSMA-11 PET/CT scan or PET/MRI scan.

About three-quarters of patients (74%) had at least one positive lesion detected by Ga 68 PSMA-11 PET in at least one region – bone, prostate bed, pelvic lymph node, or extra-pelvic soft tissue.

“In patients with positive Ga 68 PSMA-11 PET readings who had correlative tissue pathology from biopsies, results from baseline or follow-up imaging by conventional methods, and serial PSA levels available for comparison, local recurrence or metastasis of prostate cancer was confirmed in an estimated 91% of cases,” the FDA noted.

“Thus, the second trial demonstrated that Ga 68 PSMA-11 PET can detect sites of disease in patients with biochemical evidence of recurrent prostate cancer, thereby providing important information that may impact the approach to therapy,” the agency added.

The FDA also noted that no serious adverse reactions were attributed to Ga 68 PSMA-11. The most common adverse reactions were nausea, diarrhea, and dizziness.

The FDA said there is a risk for misdiagnosis because Ga 68 PSMA-11 binding may occur in other types of cancer, and certain nonmalignant processes may lead to errors in interpreting images. In addition, there are radiation risks because Ga 68 PSMA-11 contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk for cancer.

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

A radioactive diagnostic agent has been approved by the U.S. Food and Drug Administration for use in patients with prostate cancer, but only for those treated at two institutions in California.

The product, Gallium 68 PSMA-11 (Ga 68 PSMA-11), is the first agent approved specifically for use in positron-emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)–positive lesions in men with prostate cancer, the FDA noted.

This imaging approach can “detect whether or not the cancer has spread to other parts of the body,” commented Alex Gorovets, MD, acting deputy director of the Office of Specialty Medicine in the FDA’s Center for Drug Evaluation and Research.

Ga 68 PSMA-11 is indicated for use in patients with suspected prostate cancer metastasis whose conditions are potentially curable by surgery or radiotherapy and in patients with suspected prostate cancer recurrence, as determined on the basis of elevated serum prostate-specific antigen (PSA) levels.
 

Institutional use only

Ga 68 PSMA-11 has been approved for institutional use at the University of California, Los Angeles and the University of California, San Francisco under an academic new drug application (NDA).

The FDA approval was based partly on a clinical trial conducted by the UCSF and UCLA research teams on the effectiveness of PSMA-PET.

“It is rare for academic institutions to obtain FDA approval of a drug, and this unique collaboration has led to what is one of the first coapprovals of a drug at two institutions,” said Thomas Hope, MD, an associate professor at UCSF. “We hope that this first step will lead to a more widespread availability of this imaging test to men with prostate cancer throughout the country.”

Ga 68 PSMA-11 was developed outside the United States at the University of Heidelberg (Germany).

A commercial NDA from Telix Pharmaceuticals for TL591-CDx, a radiopharmaceutical cold kit for the preparation of Ga 68 PSMA-11 injection, is under consideration by the FDA.

The agency noted that two other PET diagnostic agents – fluciclovine F18 and choline C11 – are approved for prostate cancer imaging. However, they are only approved for use in patients with suspected cancer recurrence.
 

Trial results with PSMA-PET/CT

“PSMA-PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” commented T. Martin Ma, MD, PhD, of UCLA.

Dr. Ma presented a U.S. study on the technique at the recent annual meeting of the American Society for Radiation Oncology. That study showed that PSMA-PET/CT led to nodal upstaging in 19.7% of patients and metastasis upstaging in 9.4%.

He said these results were similar to those from the Australian proPSMA trial, which was published in The Lancet earlier this year. That trial found PSMA-PET/CT to be superior to conventional imaging with CT and bone scanning for primary staging of high-risk prostate cancer.

“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma commented.

“PSMA-PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Center, Melbourne, who was not involved in either study.

“PSMA-PET/CT has challenged conventional imaging in staging before curative-intent surgery or radiotherapy,” Dr. Eapen added.

The accuracy of PSMA-PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview last month. This superior accuracy can ultimately affect management. The imaging has additional benefits of lower radiation dose as well as reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.
 

Trial results with Ga 68 PSMA-11

The safety and efficacy of Ga 68 PSMA-11 were evaluated in two prospective clinical trials with a total of 960 men with prostate cancer, each of whom received one injection of the product.

The first trial involved 325 patients with biopsy-proven prostate cancer who underwent PET/CT or PET/MRI scans performed with Ga 68 PSMA-11.

“These patients were candidates for surgical removal of the prostate gland and pelvic lymph nodes and were considered at higher risk for metastasis. Among the patients who proceeded to surgery, those with positive readings in the pelvic lymph nodes on Ga 68 PSMA-11 PET had a clinically important rate of metastatic cancer confirmed by surgical pathology,” the FDA noted.

“The availability of this information prior to treatment is expected to have important implications for patient care,” the FDA commented. “For example, it may spare certain patients from undergoing unnecessary surgery.”

The second trial enrolled 635 patients with rising serum PSA levels after initial prostate surgery or radiotherapy. All patients received a single Ga 68 PSMA-11 PET/CT scan or PET/MRI scan.

About three-quarters of patients (74%) had at least one positive lesion detected by Ga 68 PSMA-11 PET in at least one region – bone, prostate bed, pelvic lymph node, or extra-pelvic soft tissue.

“In patients with positive Ga 68 PSMA-11 PET readings who had correlative tissue pathology from biopsies, results from baseline or follow-up imaging by conventional methods, and serial PSA levels available for comparison, local recurrence or metastasis of prostate cancer was confirmed in an estimated 91% of cases,” the FDA noted.

“Thus, the second trial demonstrated that Ga 68 PSMA-11 PET can detect sites of disease in patients with biochemical evidence of recurrent prostate cancer, thereby providing important information that may impact the approach to therapy,” the agency added.

The FDA also noted that no serious adverse reactions were attributed to Ga 68 PSMA-11. The most common adverse reactions were nausea, diarrhea, and dizziness.

The FDA said there is a risk for misdiagnosis because Ga 68 PSMA-11 binding may occur in other types of cancer, and certain nonmalignant processes may lead to errors in interpreting images. In addition, there are radiation risks because Ga 68 PSMA-11 contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk for cancer.

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

While the concept of home-based care and remote monitoring of patients may not be a new concept, the importance of this option for managing patients has taken on great importance during this COVID-19 pandemic.

Courtesy Dr. Noel Deep

We are currently living and working in unprecedented times and the impact of the pandemic is quite evident, and it plays an important part in every health care worker’s daily life. The high volumes of patients presenting to emergency rooms and urgent care/walk-in clinics and seeking posthospitalization visits with their physicians is stressing the health care environment. In such difficult times, the hospital-at-home model of care provides a valuable and viable option to provide appropriate care to those patients who may require close monitoring of their health without being hospitalized and using valuable inpatient resources that could then be used for the higher-acuity patients. As a physician who lives this every day and as a practicing internist and a part-time administrator, I welcome the hospital-at-home approach that complements the care provided in the emergency room, inpatient and ambulatory practice settings. I believe this type of approach to patient care would benefit those patients who, while being acutely ill, may not require the 24/7 intensive care that more critically ill individuals may need. As long as the patients are provided with appropriate telemonitoring devices such as a blood pressure cuff, pulse oximeter, and thermometer, and have access to video telemonitoring, the appropriately selected patients would benefit from this method of care provision for their acute illness.
 

Mental health benefits

I see several benefits for patients who can be triaged/assigned to this telemonitoring model of care. A patient would probably be happier being at home because they could sleep in their own bed and eat their own food and be able to walk around their house or even venture outdoors to enjoy the fresh air and nature. Being able to do these things will contribute positively to their emotional and psychological well-being.

For some elderly individuals, having access to the familiarity of their surroundings would mean these patients would have fewer incidences of hospital-associated delirium or falls. Additionally, they would be able to enjoy the company of their family members, which, during this COVID pandemic, is not possible in many hospitals. This would reduce emotional tensions for the patients and their families and the risk of transmission of infections to the patients and their visitors in the hospitals.
 

Freeing up resources

More importantly, this model would help physicians and hospitals provide the much needed care to the appropriate patients in the appropriate settings, thereby leading to decreased use of emergency rooms, health care workers, and personal protective equipment – all of which are currently in high demand.

Having a dedicated team of physicians, nurses, respiratory therapists, and other health care workers available to monitor these home-based patients on a daily or more frequent basis, depending on their health status, would result in these patients receiving equivalent care to what they would have received in a hospital.

Another positive outcome of using this home-based care model in the pandemic is that it would free up hospital beds for non–COVID-19 patients who might need hospitalization for management of their acute illnesses or exacerbation of chronic health conditions.
 

Possible limitations

This model of care has some limitations, including that it is not geared toward high volumes in my opinion and will not work in every home. Patients need to have Internet capabilities, phone services, and other features in their homes that make it possible for them to access this type of care. Additionally, patients may not be able to get their insurance companies to pay for these services. While the Centers for Medicare & Medicaid Services recently authorized patients to be transferred from EDs or inpatient wards to hospital-level care at home, for how long will reimbursements for this kind of care continue? If insurance will not pay for this monitoring at home, then will physician practices and hospital based practices provide this non reimbursed service?

Also, patients and their families may not be accepting of this model of care because they may feel it is inferior to inpatient hospitalization.

Despite these limitations, as long as Medicare and other health insurance programs provide reimbursement for such hospital-at-home services, I foresee this concept being highly used and benefiting health care entities in the United States.
 

Dr. Deep is a general internist in a multispecialty group practice with Aspirus Antigo (Wis.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. He is also assistant clinical professor at the Medical College of Wisconsin, Central Wisconsin Campus, and the governor of the Wisconsin chapter of the American College of Physicians. Dr. Deep serves on the editorial advisory board of Internal Medicine News. Contact him at [email protected].

While the concept of home-based care and remote monitoring of patients may not be a new concept, the importance of this option for managing patients has taken on great importance during this COVID-19 pandemic.

Courtesy Dr. Noel Deep

We are currently living and working in unprecedented times and the impact of the pandemic is quite evident, and it plays an important part in every health care worker’s daily life. The high volumes of patients presenting to emergency rooms and urgent care/walk-in clinics and seeking posthospitalization visits with their physicians is stressing the health care environment. In such difficult times, the hospital-at-home model of care provides a valuable and viable option to provide appropriate care to those patients who may require close monitoring of their health without being hospitalized and using valuable inpatient resources that could then be used for the higher-acuity patients. As a physician who lives this every day and as a practicing internist and a part-time administrator, I welcome the hospital-at-home approach that complements the care provided in the emergency room, inpatient and ambulatory practice settings. I believe this type of approach to patient care would benefit those patients who, while being acutely ill, may not require the 24/7 intensive care that more critically ill individuals may need. As long as the patients are provided with appropriate telemonitoring devices such as a blood pressure cuff, pulse oximeter, and thermometer, and have access to video telemonitoring, the appropriately selected patients would benefit from this method of care provision for their acute illness.
 

Mental health benefits

I see several benefits for patients who can be triaged/assigned to this telemonitoring model of care. A patient would probably be happier being at home because they could sleep in their own bed and eat their own food and be able to walk around their house or even venture outdoors to enjoy the fresh air and nature. Being able to do these things will contribute positively to their emotional and psychological well-being.

For some elderly individuals, having access to the familiarity of their surroundings would mean these patients would have fewer incidences of hospital-associated delirium or falls. Additionally, they would be able to enjoy the company of their family members, which, during this COVID pandemic, is not possible in many hospitals. This would reduce emotional tensions for the patients and their families and the risk of transmission of infections to the patients and their visitors in the hospitals.
 

Freeing up resources

More importantly, this model would help physicians and hospitals provide the much needed care to the appropriate patients in the appropriate settings, thereby leading to decreased use of emergency rooms, health care workers, and personal protective equipment – all of which are currently in high demand.

Having a dedicated team of physicians, nurses, respiratory therapists, and other health care workers available to monitor these home-based patients on a daily or more frequent basis, depending on their health status, would result in these patients receiving equivalent care to what they would have received in a hospital.

Another positive outcome of using this home-based care model in the pandemic is that it would free up hospital beds for non–COVID-19 patients who might need hospitalization for management of their acute illnesses or exacerbation of chronic health conditions.
 

Possible limitations

This model of care has some limitations, including that it is not geared toward high volumes in my opinion and will not work in every home. Patients need to have Internet capabilities, phone services, and other features in their homes that make it possible for them to access this type of care. Additionally, patients may not be able to get their insurance companies to pay for these services. While the Centers for Medicare & Medicaid Services recently authorized patients to be transferred from EDs or inpatient wards to hospital-level care at home, for how long will reimbursements for this kind of care continue? If insurance will not pay for this monitoring at home, then will physician practices and hospital based practices provide this non reimbursed service?

Also, patients and their families may not be accepting of this model of care because they may feel it is inferior to inpatient hospitalization.

Despite these limitations, as long as Medicare and other health insurance programs provide reimbursement for such hospital-at-home services, I foresee this concept being highly used and benefiting health care entities in the United States.
 

Dr. Deep is a general internist in a multispecialty group practice with Aspirus Antigo (Wis.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. He is also assistant clinical professor at the Medical College of Wisconsin, Central Wisconsin Campus, and the governor of the Wisconsin chapter of the American College of Physicians. Dr. Deep serves on the editorial advisory board of Internal Medicine News. Contact him at [email protected].

While the concept of home-based care and remote monitoring of patients may not be a new concept, the importance of this option for managing patients has taken on great importance during this COVID-19 pandemic.

Courtesy Dr. Noel Deep

We are currently living and working in unprecedented times and the impact of the pandemic is quite evident, and it plays an important part in every health care worker’s daily life. The high volumes of patients presenting to emergency rooms and urgent care/walk-in clinics and seeking posthospitalization visits with their physicians is stressing the health care environment. In such difficult times, the hospital-at-home model of care provides a valuable and viable option to provide appropriate care to those patients who may require close monitoring of their health without being hospitalized and using valuable inpatient resources that could then be used for the higher-acuity patients. As a physician who lives this every day and as a practicing internist and a part-time administrator, I welcome the hospital-at-home approach that complements the care provided in the emergency room, inpatient and ambulatory practice settings. I believe this type of approach to patient care would benefit those patients who, while being acutely ill, may not require the 24/7 intensive care that more critically ill individuals may need. As long as the patients are provided with appropriate telemonitoring devices such as a blood pressure cuff, pulse oximeter, and thermometer, and have access to video telemonitoring, the appropriately selected patients would benefit from this method of care provision for their acute illness.
 

Mental health benefits

I see several benefits for patients who can be triaged/assigned to this telemonitoring model of care. A patient would probably be happier being at home because they could sleep in their own bed and eat their own food and be able to walk around their house or even venture outdoors to enjoy the fresh air and nature. Being able to do these things will contribute positively to their emotional and psychological well-being.

For some elderly individuals, having access to the familiarity of their surroundings would mean these patients would have fewer incidences of hospital-associated delirium or falls. Additionally, they would be able to enjoy the company of their family members, which, during this COVID pandemic, is not possible in many hospitals. This would reduce emotional tensions for the patients and their families and the risk of transmission of infections to the patients and their visitors in the hospitals.
 

Freeing up resources

More importantly, this model would help physicians and hospitals provide the much needed care to the appropriate patients in the appropriate settings, thereby leading to decreased use of emergency rooms, health care workers, and personal protective equipment – all of which are currently in high demand.

Having a dedicated team of physicians, nurses, respiratory therapists, and other health care workers available to monitor these home-based patients on a daily or more frequent basis, depending on their health status, would result in these patients receiving equivalent care to what they would have received in a hospital.

Another positive outcome of using this home-based care model in the pandemic is that it would free up hospital beds for non–COVID-19 patients who might need hospitalization for management of their acute illnesses or exacerbation of chronic health conditions.
 

Possible limitations

This model of care has some limitations, including that it is not geared toward high volumes in my opinion and will not work in every home. Patients need to have Internet capabilities, phone services, and other features in their homes that make it possible for them to access this type of care. Additionally, patients may not be able to get their insurance companies to pay for these services. While the Centers for Medicare & Medicaid Services recently authorized patients to be transferred from EDs or inpatient wards to hospital-level care at home, for how long will reimbursements for this kind of care continue? If insurance will not pay for this monitoring at home, then will physician practices and hospital based practices provide this non reimbursed service?

Also, patients and their families may not be accepting of this model of care because they may feel it is inferior to inpatient hospitalization.

Despite these limitations, as long as Medicare and other health insurance programs provide reimbursement for such hospital-at-home services, I foresee this concept being highly used and benefiting health care entities in the United States.
 

Dr. Deep is a general internist in a multispecialty group practice with Aspirus Antigo (Wis.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. He is also assistant clinical professor at the Medical College of Wisconsin, Central Wisconsin Campus, and the governor of the Wisconsin chapter of the American College of Physicians. Dr. Deep serves on the editorial advisory board of Internal Medicine News. Contact him at [email protected].