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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Controlled hyperthermia: Novel treatment of BCCs without surgery continues to be refined
PHOENIX – .
“For 2,000 years, it’s been known that heat can kill cancers,” an apoptotic reaction “rather than a destructive reaction coming from excessive heat,” Christopher B. Zachary, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study was presented during an abstract session.
Dr. Zachary, professor and chair emeritus of the department of dermatology at the University of California, Irvine, and colleagues, evaluated a novel, noninvasive technique of controlled hyperthermia and mapping protocol (CHAMP) designed to help clinicians with margin assessment and treatment of superficial and nodular BCCs. For this prospective study, which was first described at the 2022 ASLMS annual conference and is being conducted at three centers, 73 patients with biopsy-proven superficial and nodular BCCs have been scanned with the VivoSight Dx optical coherence tomography (OCT) device to map BCC tumor margins.
The BCCs were treated with the Sciton 1,064-nm Er:YAG laser equipped with a 4-mm beam diameter scan pattern with no overlap and an 8-millisecond pulse duration, randomized to either standard 120-140 J/cm2 pulses until tissue graying and contraction was observed, or the CHAMP controlled hyperthermia technique using repeated 25 J/cm2 pulses under thermal camera imaging to maintain a consistent temperature of 55º C for 60 seconds. Patients were rescanned by OCT at 3 to 12 months for any signs of residual tumor and if positive, were retreated. Finally, lesions were excised for evidence of histological clearance.
To date, 48 patients have completed the study. Among the 26 patients treated with the CHAMP method, 22 (84.6%) were histologically clear, as were 19 of the 22 (86.4%) in the standard treatment group. Ulceration was uncommon with the CHAMP method, and patients healed with modest erythema, Dr. Zachary said.
Pretreatment OCT mapping of BCCs indicated that tumors extended beyond their 5-mm clinical margins in 11 cases (15%). “This will be of interest to those who treat BCCs by Mohs or standard excision,” he said. Increased vascularity measured by dynamic OCT was noted in most CHAMP patients immediately after irradiation, which suggests that apoptosis was the primary mechanism of tumor response instead of vascular destruction.
“The traditional technique for using the long pulsed 1,064-nm Er:YAG laser to cause damage and destruction of BCC is 120-140 J/cm2 at one or two passes until you get to an endpoint of graying and contraction of tissue,” Dr. Zachary said. “That’s opposed to the ‘Low and Slow’ approach [where you use] multiple pulses at 25 J/cm2 until you achieve an optimal time and temperature. If you treat above 60º C, you tend to get epidermal blistering, prolonged healing, and interestingly, absence of pain. I think that’s because you kill off the nerve fibers. With the low fluence multiple scan technique, you’re going for an even flat-top heating.”
Currently, he and his colleagues consider 55 degrees at 60 seconds as “the optimal parameters,” he said, but “it could be 45 degrees at 90 seconds or two minutes. We don’t know yet.”
In an interview at the meeting, one of the abstract session moderators, Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, said that he was encouraged by the study results as investigations into effective, noninvasive treatment of BCC continue to move forward. “Details matter such as the temperature [of energy delivery] and noninvasive imaging to delineate the appropriate margins,” said Dr. Avram, who has conducted research on the 1,064-nm long-pulsed Nd:YAG laser as an alternative treatment for nonfacial BCCs in patients who are poor surgical candidates.
“Hopefully, at some point,” he said, such approaches will “become the standard of care for many BCCs that we are now treating surgically. I don’t think this will happen in the next 3 years, but I think in the long term, it will emerge as the treatment of choice.”
The study is being funded by Michelson Diagnostics. Sciton provided the long-pulsed 1,064-nm lasers devices being used in the trial. Dr. Zachary reported having no relevant disclosures. Dr. Avram disclosed that he has received consulting fees from Sciton.
PHOENIX – .
“For 2,000 years, it’s been known that heat can kill cancers,” an apoptotic reaction “rather than a destructive reaction coming from excessive heat,” Christopher B. Zachary, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study was presented during an abstract session.
Dr. Zachary, professor and chair emeritus of the department of dermatology at the University of California, Irvine, and colleagues, evaluated a novel, noninvasive technique of controlled hyperthermia and mapping protocol (CHAMP) designed to help clinicians with margin assessment and treatment of superficial and nodular BCCs. For this prospective study, which was first described at the 2022 ASLMS annual conference and is being conducted at three centers, 73 patients with biopsy-proven superficial and nodular BCCs have been scanned with the VivoSight Dx optical coherence tomography (OCT) device to map BCC tumor margins.
The BCCs were treated with the Sciton 1,064-nm Er:YAG laser equipped with a 4-mm beam diameter scan pattern with no overlap and an 8-millisecond pulse duration, randomized to either standard 120-140 J/cm2 pulses until tissue graying and contraction was observed, or the CHAMP controlled hyperthermia technique using repeated 25 J/cm2 pulses under thermal camera imaging to maintain a consistent temperature of 55º C for 60 seconds. Patients were rescanned by OCT at 3 to 12 months for any signs of residual tumor and if positive, were retreated. Finally, lesions were excised for evidence of histological clearance.
To date, 48 patients have completed the study. Among the 26 patients treated with the CHAMP method, 22 (84.6%) were histologically clear, as were 19 of the 22 (86.4%) in the standard treatment group. Ulceration was uncommon with the CHAMP method, and patients healed with modest erythema, Dr. Zachary said.
Pretreatment OCT mapping of BCCs indicated that tumors extended beyond their 5-mm clinical margins in 11 cases (15%). “This will be of interest to those who treat BCCs by Mohs or standard excision,” he said. Increased vascularity measured by dynamic OCT was noted in most CHAMP patients immediately after irradiation, which suggests that apoptosis was the primary mechanism of tumor response instead of vascular destruction.
“The traditional technique for using the long pulsed 1,064-nm Er:YAG laser to cause damage and destruction of BCC is 120-140 J/cm2 at one or two passes until you get to an endpoint of graying and contraction of tissue,” Dr. Zachary said. “That’s opposed to the ‘Low and Slow’ approach [where you use] multiple pulses at 25 J/cm2 until you achieve an optimal time and temperature. If you treat above 60º C, you tend to get epidermal blistering, prolonged healing, and interestingly, absence of pain. I think that’s because you kill off the nerve fibers. With the low fluence multiple scan technique, you’re going for an even flat-top heating.”
Currently, he and his colleagues consider 55 degrees at 60 seconds as “the optimal parameters,” he said, but “it could be 45 degrees at 90 seconds or two minutes. We don’t know yet.”
In an interview at the meeting, one of the abstract session moderators, Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, said that he was encouraged by the study results as investigations into effective, noninvasive treatment of BCC continue to move forward. “Details matter such as the temperature [of energy delivery] and noninvasive imaging to delineate the appropriate margins,” said Dr. Avram, who has conducted research on the 1,064-nm long-pulsed Nd:YAG laser as an alternative treatment for nonfacial BCCs in patients who are poor surgical candidates.
“Hopefully, at some point,” he said, such approaches will “become the standard of care for many BCCs that we are now treating surgically. I don’t think this will happen in the next 3 years, but I think in the long term, it will emerge as the treatment of choice.”
The study is being funded by Michelson Diagnostics. Sciton provided the long-pulsed 1,064-nm lasers devices being used in the trial. Dr. Zachary reported having no relevant disclosures. Dr. Avram disclosed that he has received consulting fees from Sciton.
PHOENIX – .
“For 2,000 years, it’s been known that heat can kill cancers,” an apoptotic reaction “rather than a destructive reaction coming from excessive heat,” Christopher B. Zachary, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study was presented during an abstract session.
Dr. Zachary, professor and chair emeritus of the department of dermatology at the University of California, Irvine, and colleagues, evaluated a novel, noninvasive technique of controlled hyperthermia and mapping protocol (CHAMP) designed to help clinicians with margin assessment and treatment of superficial and nodular BCCs. For this prospective study, which was first described at the 2022 ASLMS annual conference and is being conducted at three centers, 73 patients with biopsy-proven superficial and nodular BCCs have been scanned with the VivoSight Dx optical coherence tomography (OCT) device to map BCC tumor margins.
The BCCs were treated with the Sciton 1,064-nm Er:YAG laser equipped with a 4-mm beam diameter scan pattern with no overlap and an 8-millisecond pulse duration, randomized to either standard 120-140 J/cm2 pulses until tissue graying and contraction was observed, or the CHAMP controlled hyperthermia technique using repeated 25 J/cm2 pulses under thermal camera imaging to maintain a consistent temperature of 55º C for 60 seconds. Patients were rescanned by OCT at 3 to 12 months for any signs of residual tumor and if positive, were retreated. Finally, lesions were excised for evidence of histological clearance.
To date, 48 patients have completed the study. Among the 26 patients treated with the CHAMP method, 22 (84.6%) were histologically clear, as were 19 of the 22 (86.4%) in the standard treatment group. Ulceration was uncommon with the CHAMP method, and patients healed with modest erythema, Dr. Zachary said.
Pretreatment OCT mapping of BCCs indicated that tumors extended beyond their 5-mm clinical margins in 11 cases (15%). “This will be of interest to those who treat BCCs by Mohs or standard excision,” he said. Increased vascularity measured by dynamic OCT was noted in most CHAMP patients immediately after irradiation, which suggests that apoptosis was the primary mechanism of tumor response instead of vascular destruction.
“The traditional technique for using the long pulsed 1,064-nm Er:YAG laser to cause damage and destruction of BCC is 120-140 J/cm2 at one or two passes until you get to an endpoint of graying and contraction of tissue,” Dr. Zachary said. “That’s opposed to the ‘Low and Slow’ approach [where you use] multiple pulses at 25 J/cm2 until you achieve an optimal time and temperature. If you treat above 60º C, you tend to get epidermal blistering, prolonged healing, and interestingly, absence of pain. I think that’s because you kill off the nerve fibers. With the low fluence multiple scan technique, you’re going for an even flat-top heating.”
Currently, he and his colleagues consider 55 degrees at 60 seconds as “the optimal parameters,” he said, but “it could be 45 degrees at 90 seconds or two minutes. We don’t know yet.”
In an interview at the meeting, one of the abstract session moderators, Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, said that he was encouraged by the study results as investigations into effective, noninvasive treatment of BCC continue to move forward. “Details matter such as the temperature [of energy delivery] and noninvasive imaging to delineate the appropriate margins,” said Dr. Avram, who has conducted research on the 1,064-nm long-pulsed Nd:YAG laser as an alternative treatment for nonfacial BCCs in patients who are poor surgical candidates.
“Hopefully, at some point,” he said, such approaches will “become the standard of care for many BCCs that we are now treating surgically. I don’t think this will happen in the next 3 years, but I think in the long term, it will emerge as the treatment of choice.”
The study is being funded by Michelson Diagnostics. Sciton provided the long-pulsed 1,064-nm lasers devices being used in the trial. Dr. Zachary reported having no relevant disclosures. Dr. Avram disclosed that he has received consulting fees from Sciton.
AT ASLMS 2023
Teriflunomide delays MS symptoms in radiologically isolated syndrome
BOSTON – , according to a double-blind, phase 3 trial presented in the Emerging Science session of the 2023 annual meeting of the American Academy of Neurology.
“These data add to the evidence that early immunomodulation offers clinical benefit even in the presymptomatic phase of MS,” reported Christine Lebrun-Frenay, MD, PhD, head of inflammatory neurological disorders research unit, University of Nice, France. This is the second study to show a benefit from a disease-modifying therapy in asymptomatic RIS patients. The ARISE study, which was presented at the 2022 European Committee for Treatment and Research in MS and has now been published, compared 240 mg of twice-daily dimethyl fumarate with placebo. Dimethyl fumarate was associated with an 82% (hazard ratio, 0.18; P = .007) reduction in the risk of a first demyelinating event after 96 weeks of follow-up.
TERIS trial data
In the new study, called TERIS, the design and outcomes were similar to the ARISE study. Eighty-nine patients meeting standard criteria for RIS were randomized to 14 mg of once-daily teriflunomide or placebo. The majority (71%) were female, and the mean age was 39.8 years. At the time of RIS diagnosis, the mean age was 38 years. At study entry, standardized MRI studies were performed of the brain and spinal cord.
During 2 years of follow-up, 8 of 28 demyelinating events were observed in the active treatment group. The remaining 20 occurred in the placebo group. This translated to a 63% reduction (HR, 0.37; P = .018) in favor of teriflunomide. When graphed, the curves separated at about 6 months and then widened progressively over time.
Distinct from clinically isolated syndrome (CIS), which describes individuals who have a symptomatic episode consistent with a demyelinating event, RIS is based primarily on an MRI that shows lesions highly suggestive of MS. Neither confirms the MS diagnosis, but both are associated with a high likelihood of eventually meeting MS diagnostic criteria. The ARISE and TERIS studies now support therapy to delay demyelinating events.
“With more and more people having brain scans for various reasons, such as headache or head trauma, more of these cases are being discovered,” Dr. Lebrun-Frenay said.
Caution warranted when interpreting the findings
The data support the theory that treatment should begin early in patients with a high likelihood of developing symptomatic MS on the basis of brain lesions. It is logical to assume that preventing damage to the myelin will reduce or delay permanent symptoms and permanent neurologic impairment, but Dr. Lebrun-Frenay suggested that the available data from ARISE and TERIS are not practice changing even though both were multicenter double-blind trials.
“More data from larger groups of patients are needed to confirm the findings,” she said. She expressed concern about not adhering to strict criteria to diagnosis RIS.
“It is important that medical professionals are cautious,” she said, citing the risk of misdiagnosis of pathology of MRI that leads to treatment of patients with a low risk of developing symptomatic MS.
Teriflunomide and dimethyl fumarate, which have long been available as first-line therapies in relapsing-remitting MS, are generally well tolerated. In the TERIS and ARISE studies, mild or moderate events occurred more commonly in the active treatment than the placebo arms, but there were no serious adverse events. However, both can produce more serious adverse events, which, in the case of teriflunomide, include liver toxicity leading to injury and liver failure.
Challenging the traditional definition of MS
The author of the ARISE study, Darin T. Okuda, MD, a professor of neurology at the UT Southwestern Medical Center, Dallas, indicated that his study, now reinforced by the TERIS study, challenges the definition of MS.
“Both ARISE and TERIS demonstrated a significant reduction in seminal clinical event rates related to inflammatory demyelination,” Dr. Okuda said in an interview. They provide evidence that patients are at high risk of the demyelinating events that characterize MS. Given the potential difficulty for accessing therapies of benefit, “how we define multiple sclerosis is highly important.”
“Individuals of younger age with abnormal spinal cord MRI studies along with other paraclinical features related to risk for a first event may be the most ideal group to treat,” he said. However, he agreed with Dr. Lebrun-Frenay that it is not yet clear which RIS patients are the most appropriate candidates.
“Gaining a more refined sense of who we should treat will require more work,” he said.
These data are likely to change the orientation toward RIS, according to Melina Hosseiny, MD, department of radiology, University of California, Los Angeles, Medical Center. She noted that the relationship between RIS and increased risk of MS has long been recognized, and the risk increases with specific features on imaging.
“Studies have shown that spinal cord lesions are associated with a greater than 50% chance of converting to MS,” said Dr. Hosseiny, who was the lead author of a review article on RIS. “Identifying such imaging findings can help identify patients who may benefit from disease-modifying medications.”
Dr. Lebrun-Frenay reports no potential conflicts of interest. Dr. Okuda has financial relationships with Alexion, Biogen, Celgene, EMD Serono, Genzyme, TG Therapeutics, and VielaBio. Dr. Hosseiny reports no potential conflicts of interest.
BOSTON – , according to a double-blind, phase 3 trial presented in the Emerging Science session of the 2023 annual meeting of the American Academy of Neurology.
“These data add to the evidence that early immunomodulation offers clinical benefit even in the presymptomatic phase of MS,” reported Christine Lebrun-Frenay, MD, PhD, head of inflammatory neurological disorders research unit, University of Nice, France. This is the second study to show a benefit from a disease-modifying therapy in asymptomatic RIS patients. The ARISE study, which was presented at the 2022 European Committee for Treatment and Research in MS and has now been published, compared 240 mg of twice-daily dimethyl fumarate with placebo. Dimethyl fumarate was associated with an 82% (hazard ratio, 0.18; P = .007) reduction in the risk of a first demyelinating event after 96 weeks of follow-up.
TERIS trial data
In the new study, called TERIS, the design and outcomes were similar to the ARISE study. Eighty-nine patients meeting standard criteria for RIS were randomized to 14 mg of once-daily teriflunomide or placebo. The majority (71%) were female, and the mean age was 39.8 years. At the time of RIS diagnosis, the mean age was 38 years. At study entry, standardized MRI studies were performed of the brain and spinal cord.
During 2 years of follow-up, 8 of 28 demyelinating events were observed in the active treatment group. The remaining 20 occurred in the placebo group. This translated to a 63% reduction (HR, 0.37; P = .018) in favor of teriflunomide. When graphed, the curves separated at about 6 months and then widened progressively over time.
Distinct from clinically isolated syndrome (CIS), which describes individuals who have a symptomatic episode consistent with a demyelinating event, RIS is based primarily on an MRI that shows lesions highly suggestive of MS. Neither confirms the MS diagnosis, but both are associated with a high likelihood of eventually meeting MS diagnostic criteria. The ARISE and TERIS studies now support therapy to delay demyelinating events.
“With more and more people having brain scans for various reasons, such as headache or head trauma, more of these cases are being discovered,” Dr. Lebrun-Frenay said.
Caution warranted when interpreting the findings
The data support the theory that treatment should begin early in patients with a high likelihood of developing symptomatic MS on the basis of brain lesions. It is logical to assume that preventing damage to the myelin will reduce or delay permanent symptoms and permanent neurologic impairment, but Dr. Lebrun-Frenay suggested that the available data from ARISE and TERIS are not practice changing even though both were multicenter double-blind trials.
“More data from larger groups of patients are needed to confirm the findings,” she said. She expressed concern about not adhering to strict criteria to diagnosis RIS.
“It is important that medical professionals are cautious,” she said, citing the risk of misdiagnosis of pathology of MRI that leads to treatment of patients with a low risk of developing symptomatic MS.
Teriflunomide and dimethyl fumarate, which have long been available as first-line therapies in relapsing-remitting MS, are generally well tolerated. In the TERIS and ARISE studies, mild or moderate events occurred more commonly in the active treatment than the placebo arms, but there were no serious adverse events. However, both can produce more serious adverse events, which, in the case of teriflunomide, include liver toxicity leading to injury and liver failure.
Challenging the traditional definition of MS
The author of the ARISE study, Darin T. Okuda, MD, a professor of neurology at the UT Southwestern Medical Center, Dallas, indicated that his study, now reinforced by the TERIS study, challenges the definition of MS.
“Both ARISE and TERIS demonstrated a significant reduction in seminal clinical event rates related to inflammatory demyelination,” Dr. Okuda said in an interview. They provide evidence that patients are at high risk of the demyelinating events that characterize MS. Given the potential difficulty for accessing therapies of benefit, “how we define multiple sclerosis is highly important.”
“Individuals of younger age with abnormal spinal cord MRI studies along with other paraclinical features related to risk for a first event may be the most ideal group to treat,” he said. However, he agreed with Dr. Lebrun-Frenay that it is not yet clear which RIS patients are the most appropriate candidates.
“Gaining a more refined sense of who we should treat will require more work,” he said.
These data are likely to change the orientation toward RIS, according to Melina Hosseiny, MD, department of radiology, University of California, Los Angeles, Medical Center. She noted that the relationship between RIS and increased risk of MS has long been recognized, and the risk increases with specific features on imaging.
“Studies have shown that spinal cord lesions are associated with a greater than 50% chance of converting to MS,” said Dr. Hosseiny, who was the lead author of a review article on RIS. “Identifying such imaging findings can help identify patients who may benefit from disease-modifying medications.”
Dr. Lebrun-Frenay reports no potential conflicts of interest. Dr. Okuda has financial relationships with Alexion, Biogen, Celgene, EMD Serono, Genzyme, TG Therapeutics, and VielaBio. Dr. Hosseiny reports no potential conflicts of interest.
BOSTON – , according to a double-blind, phase 3 trial presented in the Emerging Science session of the 2023 annual meeting of the American Academy of Neurology.
“These data add to the evidence that early immunomodulation offers clinical benefit even in the presymptomatic phase of MS,” reported Christine Lebrun-Frenay, MD, PhD, head of inflammatory neurological disorders research unit, University of Nice, France. This is the second study to show a benefit from a disease-modifying therapy in asymptomatic RIS patients. The ARISE study, which was presented at the 2022 European Committee for Treatment and Research in MS and has now been published, compared 240 mg of twice-daily dimethyl fumarate with placebo. Dimethyl fumarate was associated with an 82% (hazard ratio, 0.18; P = .007) reduction in the risk of a first demyelinating event after 96 weeks of follow-up.
TERIS trial data
In the new study, called TERIS, the design and outcomes were similar to the ARISE study. Eighty-nine patients meeting standard criteria for RIS were randomized to 14 mg of once-daily teriflunomide or placebo. The majority (71%) were female, and the mean age was 39.8 years. At the time of RIS diagnosis, the mean age was 38 years. At study entry, standardized MRI studies were performed of the brain and spinal cord.
During 2 years of follow-up, 8 of 28 demyelinating events were observed in the active treatment group. The remaining 20 occurred in the placebo group. This translated to a 63% reduction (HR, 0.37; P = .018) in favor of teriflunomide. When graphed, the curves separated at about 6 months and then widened progressively over time.
Distinct from clinically isolated syndrome (CIS), which describes individuals who have a symptomatic episode consistent with a demyelinating event, RIS is based primarily on an MRI that shows lesions highly suggestive of MS. Neither confirms the MS diagnosis, but both are associated with a high likelihood of eventually meeting MS diagnostic criteria. The ARISE and TERIS studies now support therapy to delay demyelinating events.
“With more and more people having brain scans for various reasons, such as headache or head trauma, more of these cases are being discovered,” Dr. Lebrun-Frenay said.
Caution warranted when interpreting the findings
The data support the theory that treatment should begin early in patients with a high likelihood of developing symptomatic MS on the basis of brain lesions. It is logical to assume that preventing damage to the myelin will reduce or delay permanent symptoms and permanent neurologic impairment, but Dr. Lebrun-Frenay suggested that the available data from ARISE and TERIS are not practice changing even though both were multicenter double-blind trials.
“More data from larger groups of patients are needed to confirm the findings,” she said. She expressed concern about not adhering to strict criteria to diagnosis RIS.
“It is important that medical professionals are cautious,” she said, citing the risk of misdiagnosis of pathology of MRI that leads to treatment of patients with a low risk of developing symptomatic MS.
Teriflunomide and dimethyl fumarate, which have long been available as first-line therapies in relapsing-remitting MS, are generally well tolerated. In the TERIS and ARISE studies, mild or moderate events occurred more commonly in the active treatment than the placebo arms, but there were no serious adverse events. However, both can produce more serious adverse events, which, in the case of teriflunomide, include liver toxicity leading to injury and liver failure.
Challenging the traditional definition of MS
The author of the ARISE study, Darin T. Okuda, MD, a professor of neurology at the UT Southwestern Medical Center, Dallas, indicated that his study, now reinforced by the TERIS study, challenges the definition of MS.
“Both ARISE and TERIS demonstrated a significant reduction in seminal clinical event rates related to inflammatory demyelination,” Dr. Okuda said in an interview. They provide evidence that patients are at high risk of the demyelinating events that characterize MS. Given the potential difficulty for accessing therapies of benefit, “how we define multiple sclerosis is highly important.”
“Individuals of younger age with abnormal spinal cord MRI studies along with other paraclinical features related to risk for a first event may be the most ideal group to treat,” he said. However, he agreed with Dr. Lebrun-Frenay that it is not yet clear which RIS patients are the most appropriate candidates.
“Gaining a more refined sense of who we should treat will require more work,” he said.
These data are likely to change the orientation toward RIS, according to Melina Hosseiny, MD, department of radiology, University of California, Los Angeles, Medical Center. She noted that the relationship between RIS and increased risk of MS has long been recognized, and the risk increases with specific features on imaging.
“Studies have shown that spinal cord lesions are associated with a greater than 50% chance of converting to MS,” said Dr. Hosseiny, who was the lead author of a review article on RIS. “Identifying such imaging findings can help identify patients who may benefit from disease-modifying medications.”
Dr. Lebrun-Frenay reports no potential conflicts of interest. Dr. Okuda has financial relationships with Alexion, Biogen, Celgene, EMD Serono, Genzyme, TG Therapeutics, and VielaBio. Dr. Hosseiny reports no potential conflicts of interest.
AT AAN 2023
New drugs in primary care: Lessons learned from COVID-19
SAN DIEGO – – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.
Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.
Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
Understanding the mechanism of action
Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.
“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.
“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.
Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.
Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.
Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.
When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.
Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.
“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.
Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
Effective in real world, but less so than in clinical trials
The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.
A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
Many drug-drug interactions, but they can be managed
Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.
To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.
This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.
To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:
- Prescribe an alternative COVID therapy.
- Temporarily withhold concomitant medication if clinically appropriate.
- Adjust the dose of concomitant medication and monitor for adverse effects.
Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
Important considerations
Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.
He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.
Dr. Smetana and Dr. Kiefl reported no disclosures.
SAN DIEGO – – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.
Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.
Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
Understanding the mechanism of action
Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.
“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.
“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.
Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.
Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.
Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.
When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.
Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.
“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.
Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
Effective in real world, but less so than in clinical trials
The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.
A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
Many drug-drug interactions, but they can be managed
Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.
To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.
This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.
To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:
- Prescribe an alternative COVID therapy.
- Temporarily withhold concomitant medication if clinically appropriate.
- Adjust the dose of concomitant medication and monitor for adverse effects.
Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
Important considerations
Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.
He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.
Dr. Smetana and Dr. Kiefl reported no disclosures.
SAN DIEGO – – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.
Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.
Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
Understanding the mechanism of action
Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.
“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.
“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.
Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.
Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.
Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.
When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.
Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.
“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.
Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
Effective in real world, but less so than in clinical trials
The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.
A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
Many drug-drug interactions, but they can be managed
Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.
To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.
This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.
To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:
- Prescribe an alternative COVID therapy.
- Temporarily withhold concomitant medication if clinically appropriate.
- Adjust the dose of concomitant medication and monitor for adverse effects.
Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
Important considerations
Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.
He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.
Dr. Smetana and Dr. Kiefl reported no disclosures.
AT INTERNAL MEDICINE 2023
Statins tied to lower stroke risk in atrial fibrillation
Among patients with atrial fibrillation (AFib), initiation of statins soon after diagnosis was protective against stroke and related vascular events, and longer duration of use was associated with greater protection, a new cohort study shows.
Statin use was associated with lower risks of ischemic stroke or systemic embolism, hemorrhagic stroke, and transient ischemic attack (TIA), regardless of whether patients were also taking anticoagulant medications.
Lead author Jiayi Huang, a PhD student at Hong Kong University at Shenzhen (China) Hospital, concluded that the study’s findings support the use of statins to prevent stroke for patients with new-onset AFib.
“The findings have important clinical implications, particularly given that in atrial fibrillation, patients’ ischemic strokes are often fatal or disabling and have a high risk of recurrence,” she said.
The results were presented in a moderated poster session at the European Heart Rhythm Association 2023 Congress.
Widely prescribed
Anticoagulant drugs are prescribed to lower the fivefold increased risk of stroke among individuals with AFib, compared with those without AFib, but the therapy does not eliminate the higher risk, Ms. Huang explained. And although statins are widely prescribed to reduce the likelihood of myocardial infarction and stroke, “the benefit of statins for stroke prevention in patients with atrial fibrillation has been unclear.”
Ms. Huang and colleagues analyzed data from 51,472 patients newly diagnosed with AFib between 2010 and 2018. The population was divided into statin users (n = 11,866), defined as patients who had taken statins for at least 19 consecutive days in the first year after AFib diagnosis, and statin nonusers (n = 39,606), based on whether they were prescribed statin therapy after their first diagnosis of AFib.
The median age of the cohort was 74.9 years, and 47.7% were women. The investigators used statistical methods to balance baseline covariates between the two groups.
The primary outcomes were ischemic stroke or systemic embolism, hemorrhagic stroke, and TIA. Median follow-up was 5.1 years.
Statin use was associated with a significantly lower risk of all outcomes, compared with nonuse. Statin users had a 17% reduced risk of ischemic stroke or systemic embolism, a 7% reduced risk of hemorrhagic stroke, and a 15% rate of reduced risk of TIA, Ms. Huang reported.
“We also found long-term statin use was associated with greater protection than short-term use,” she said. For statin use of 6 years or longer, in comparison with use of 3 months to 2 years, the risk of ischemic stroke or systemic embolism was lowered by 43%; for hemorrhagic stroke, it was lowered by 44%, and for TIA, it was lowered by 42%.
These associations were consistent regardless of whether patients used anticoagulant medications or the type of anticoagulant.
Oussama Wazni, MD, MBA, section head of cardiac electrophysiology and pacing at the Cleveland Clinic, was a moderator of the poster session at which Ms. Huang presented her study. In an interview, he called the study “very important.”
“The message should be that all patients who have atrial fibrillation should be checked for cholesterol levels, and we should consider placing them on statins,” he said. “Is there an opportunity? Probably there is, and that’s why we’re seeing this effect in this group of patients.”
When asked about a possible mechanism by which statins produced the effects seen in the study, he pointed to LDL cholesterol lowering and possibly an effect on inflammation. “If a patient had a carotid atheroma, for example, maybe it helped with that,” he said. Previous work has shown that inflammation is related to or is associated with higher risk of thrombogenic effects, including MI or stroke.
It may be a bit less clear how statins reduced the incidence of hemorrhagic strokes, but Dr. Wazni proposed that some strokes could have started as an ischemic stroke “and then had hemorrhagic conversion, so we don’t have the granularity in here to know whether that was the case or not.”
Given the fact that the effect was stronger the longer a patient had been taking a statin, Dr. Wazni said that if a patient is tolerating the drug well, there should be no reason to discontinue it, regardless of age.
He said the study provides “welcome data and evidence because it’s pointing in the right direction,” but prospective studies would be useful “so that we can see what is driving what. Otherwise, this is just an association.”
The study was supported by Sanming Project Shenzhen. Ms. Huang and Dr. Wazni disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Among patients with atrial fibrillation (AFib), initiation of statins soon after diagnosis was protective against stroke and related vascular events, and longer duration of use was associated with greater protection, a new cohort study shows.
Statin use was associated with lower risks of ischemic stroke or systemic embolism, hemorrhagic stroke, and transient ischemic attack (TIA), regardless of whether patients were also taking anticoagulant medications.
Lead author Jiayi Huang, a PhD student at Hong Kong University at Shenzhen (China) Hospital, concluded that the study’s findings support the use of statins to prevent stroke for patients with new-onset AFib.
“The findings have important clinical implications, particularly given that in atrial fibrillation, patients’ ischemic strokes are often fatal or disabling and have a high risk of recurrence,” she said.
The results were presented in a moderated poster session at the European Heart Rhythm Association 2023 Congress.
Widely prescribed
Anticoagulant drugs are prescribed to lower the fivefold increased risk of stroke among individuals with AFib, compared with those without AFib, but the therapy does not eliminate the higher risk, Ms. Huang explained. And although statins are widely prescribed to reduce the likelihood of myocardial infarction and stroke, “the benefit of statins for stroke prevention in patients with atrial fibrillation has been unclear.”
Ms. Huang and colleagues analyzed data from 51,472 patients newly diagnosed with AFib between 2010 and 2018. The population was divided into statin users (n = 11,866), defined as patients who had taken statins for at least 19 consecutive days in the first year after AFib diagnosis, and statin nonusers (n = 39,606), based on whether they were prescribed statin therapy after their first diagnosis of AFib.
The median age of the cohort was 74.9 years, and 47.7% were women. The investigators used statistical methods to balance baseline covariates between the two groups.
The primary outcomes were ischemic stroke or systemic embolism, hemorrhagic stroke, and TIA. Median follow-up was 5.1 years.
Statin use was associated with a significantly lower risk of all outcomes, compared with nonuse. Statin users had a 17% reduced risk of ischemic stroke or systemic embolism, a 7% reduced risk of hemorrhagic stroke, and a 15% rate of reduced risk of TIA, Ms. Huang reported.
“We also found long-term statin use was associated with greater protection than short-term use,” she said. For statin use of 6 years or longer, in comparison with use of 3 months to 2 years, the risk of ischemic stroke or systemic embolism was lowered by 43%; for hemorrhagic stroke, it was lowered by 44%, and for TIA, it was lowered by 42%.
These associations were consistent regardless of whether patients used anticoagulant medications or the type of anticoagulant.
Oussama Wazni, MD, MBA, section head of cardiac electrophysiology and pacing at the Cleveland Clinic, was a moderator of the poster session at which Ms. Huang presented her study. In an interview, he called the study “very important.”
“The message should be that all patients who have atrial fibrillation should be checked for cholesterol levels, and we should consider placing them on statins,” he said. “Is there an opportunity? Probably there is, and that’s why we’re seeing this effect in this group of patients.”
When asked about a possible mechanism by which statins produced the effects seen in the study, he pointed to LDL cholesterol lowering and possibly an effect on inflammation. “If a patient had a carotid atheroma, for example, maybe it helped with that,” he said. Previous work has shown that inflammation is related to or is associated with higher risk of thrombogenic effects, including MI or stroke.
It may be a bit less clear how statins reduced the incidence of hemorrhagic strokes, but Dr. Wazni proposed that some strokes could have started as an ischemic stroke “and then had hemorrhagic conversion, so we don’t have the granularity in here to know whether that was the case or not.”
Given the fact that the effect was stronger the longer a patient had been taking a statin, Dr. Wazni said that if a patient is tolerating the drug well, there should be no reason to discontinue it, regardless of age.
He said the study provides “welcome data and evidence because it’s pointing in the right direction,” but prospective studies would be useful “so that we can see what is driving what. Otherwise, this is just an association.”
The study was supported by Sanming Project Shenzhen. Ms. Huang and Dr. Wazni disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Among patients with atrial fibrillation (AFib), initiation of statins soon after diagnosis was protective against stroke and related vascular events, and longer duration of use was associated with greater protection, a new cohort study shows.
Statin use was associated with lower risks of ischemic stroke or systemic embolism, hemorrhagic stroke, and transient ischemic attack (TIA), regardless of whether patients were also taking anticoagulant medications.
Lead author Jiayi Huang, a PhD student at Hong Kong University at Shenzhen (China) Hospital, concluded that the study’s findings support the use of statins to prevent stroke for patients with new-onset AFib.
“The findings have important clinical implications, particularly given that in atrial fibrillation, patients’ ischemic strokes are often fatal or disabling and have a high risk of recurrence,” she said.
The results were presented in a moderated poster session at the European Heart Rhythm Association 2023 Congress.
Widely prescribed
Anticoagulant drugs are prescribed to lower the fivefold increased risk of stroke among individuals with AFib, compared with those without AFib, but the therapy does not eliminate the higher risk, Ms. Huang explained. And although statins are widely prescribed to reduce the likelihood of myocardial infarction and stroke, “the benefit of statins for stroke prevention in patients with atrial fibrillation has been unclear.”
Ms. Huang and colleagues analyzed data from 51,472 patients newly diagnosed with AFib between 2010 and 2018. The population was divided into statin users (n = 11,866), defined as patients who had taken statins for at least 19 consecutive days in the first year after AFib diagnosis, and statin nonusers (n = 39,606), based on whether they were prescribed statin therapy after their first diagnosis of AFib.
The median age of the cohort was 74.9 years, and 47.7% were women. The investigators used statistical methods to balance baseline covariates between the two groups.
The primary outcomes were ischemic stroke or systemic embolism, hemorrhagic stroke, and TIA. Median follow-up was 5.1 years.
Statin use was associated with a significantly lower risk of all outcomes, compared with nonuse. Statin users had a 17% reduced risk of ischemic stroke or systemic embolism, a 7% reduced risk of hemorrhagic stroke, and a 15% rate of reduced risk of TIA, Ms. Huang reported.
“We also found long-term statin use was associated with greater protection than short-term use,” she said. For statin use of 6 years or longer, in comparison with use of 3 months to 2 years, the risk of ischemic stroke or systemic embolism was lowered by 43%; for hemorrhagic stroke, it was lowered by 44%, and for TIA, it was lowered by 42%.
These associations were consistent regardless of whether patients used anticoagulant medications or the type of anticoagulant.
Oussama Wazni, MD, MBA, section head of cardiac electrophysiology and pacing at the Cleveland Clinic, was a moderator of the poster session at which Ms. Huang presented her study. In an interview, he called the study “very important.”
“The message should be that all patients who have atrial fibrillation should be checked for cholesterol levels, and we should consider placing them on statins,” he said. “Is there an opportunity? Probably there is, and that’s why we’re seeing this effect in this group of patients.”
When asked about a possible mechanism by which statins produced the effects seen in the study, he pointed to LDL cholesterol lowering and possibly an effect on inflammation. “If a patient had a carotid atheroma, for example, maybe it helped with that,” he said. Previous work has shown that inflammation is related to or is associated with higher risk of thrombogenic effects, including MI or stroke.
It may be a bit less clear how statins reduced the incidence of hemorrhagic strokes, but Dr. Wazni proposed that some strokes could have started as an ischemic stroke “and then had hemorrhagic conversion, so we don’t have the granularity in here to know whether that was the case or not.”
Given the fact that the effect was stronger the longer a patient had been taking a statin, Dr. Wazni said that if a patient is tolerating the drug well, there should be no reason to discontinue it, regardless of age.
He said the study provides “welcome data and evidence because it’s pointing in the right direction,” but prospective studies would be useful “so that we can see what is driving what. Otherwise, this is just an association.”
The study was supported by Sanming Project Shenzhen. Ms. Huang and Dr. Wazni disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM EHRA 2023
Novel levodopa delivery system promises continuous dosing without surgery or pump
BOSTON – , according to an early clinical experience described in the Emerging Science session at the 2023 annual meeting of the American Academy of Neurology.
On this device, the attenuation of levodopa fluctuations “translated into dramatic improvements in clinical behavior, including highly significant reductions in OFF time and an increase in ON time with no dyskinesias,” reported C. Warren Olanow, MD, who is a chairman emeritus of the department of neurology at the Icahn School of Medicine at Mount Sinai, New York, and now an employee of the company developing this new device.
A novel strategy
Numerous studies have demonstrated that reductions in the troughs of plasma levodopa associated with oral dosing result in longer ON time with fewer dyskinesias, according to Dr. Olanow, who explained this has led to strategies for numerous strategies to achieve continuous delivery. A device that delivers levodopa into the stomach through a surgically implanted catheter has already received regulatory approval. Other devices delivering levodopa subcutaneously are in development, but Dr. Olanow said each of these has had limitations.
“The problem with these approaches is they are associated with potentially serious side effects and they require the patient to wear a cumbersome device,” he explained. Relative to the subcutaneous delivery systems, which have been associated with injection site reactions that include painful nodules, and the surgically implanted devices, which also require an external pump, the latest strategy avoids both disadvantages.
Called DopaFuse, the experimental device is designed to deliver the levodopa and carbidopa into the mouth through a micropump within a wearable retainer. Dr. Olanow said that previous experimental studies demonstrated that small doses of levodopa delivered by mouth to the gastrointestinal system reduce levodopa plasma variability. This early clinical study supports that premise. Levodopa delivered into the mouth by way of a propellant in the retainer-mounted pump improved clinical endpoints.
Encouraging trial results
In the study, 16 patients between the ages of 30 and 75 with Parkinson’s disease were enrolled. On day 1, they received an oral dose of levodopa/carbidopa consistent with their current treatment. On day 2, levodopa/carbidopa was delivered through the retainer-mounted device at equivalent doses. On day 3, they received a single morning oral dose and the received the remainder of their levodopa/carbidopa regimen through the device. On days 4 to 14, they received treatment in the same schedule as day 3.
When pharmacokinetics of levodopa on day 3 were compared with those on day 1, the fluctuation index and coefficient of levodopa concentration variability was reduced to a degree that was highly statistically significant (P < .0001). This, in turn, correlated with “striking” reductions in OFF time with equally statistically significant improvement in ON time and ON time without dyskinesias, according to Dr. Olanow.
Relative to an OFF time of 3.2 hours on day 1, the OFF time of 1.6 hours on day 3 represented a 50% reduction (P < .0001). ON time improved from 12.8 hours to 14.5 hours (P < .001). ON time without dyskinesias improved numerically from 8.8 hours to 9.6 hours.
“There were also improvements in activities of daily living when patients were on DopaFuse, which is a hard endpoint to reach in a study with such a small sample size,” Dr. Olanow reported.
There were no serious adverse events. Three patients reported vomiting and two patients each reported headache, but these events were mild and all resolved within a day. Three patients reported buccal lesions, but these also resolved within a day.
“Some patients reported trouble with speaking in the beginning but at the end of the study, patients were reporting that it was easier to speak because of the motor improvements,” Dr. Olanow said.
Overall, the device was well tolerated by the subjects, providing the evidence for the next stages of clinical studies, reported Dr. Olanow.
“If this turns out to be what we hope it is, it will allow us to deliver levodopa without motor complications, without need for a surgical procedure, and without the risk of subcutaneous lesions,” Dr. Olanow said.
More delivery strategies are needed
This device is in an early phase of development, but several specialists in Parkinson’s disease agreed that there is a need for more strategies to provide continuous levodopa in patients with advancing symptoms. Stuart Isaacson, MD, director, Parkinson’s Disease and Movement Disorders Center of Boca Raton, Fla., is among them.
“Novel delivery devices that can provide more continuous levodopa delivery would be an important therapeutic advance,” Dr. Isaacson said. He called levodopa “the cornerstone of treatment through the course of Parkinson’s disease,” but more physiologic dosing in advancing disease has been a challenge.
“While there are many therapies currently available to manage OFF time, many people living with Parkinson’s disease continue to spend only half of their waking day with good ON time,” he added.
The currently approved method of delivering continuous levodopa through a surgically placed catheter into the gastrointestinal system is effective, but has limitations, according to Aaron L. Ellenbogen, MD, a neurologist at Beaumont Hospital, Farmington Hills, Mich.
“One of the challenges with the current treatment landscape of Parkinson’s disease is that medication can be absorbed variably through the gastrointestinal system,” he said. “As the disease progresses, this often becomes more troublesome.” Although this new device is likely to share this issue, Dr. Ellenbogen said that several devices might be useful to match patients with the one that works best for them.
Dr. Olanow is the founder and CEO of Clintrex Research Corporation, through which he also serves as chief medical officer of SynAgile, the company developing DopaFuse. Dr. Isaacson has financial relationships with more than 30 companies, including those that produce levodopa and levodopa delivery systems. Dr. Ellenbogen has financial relationships with Allergan, Acorda, Supernus, and Teva.
BOSTON – , according to an early clinical experience described in the Emerging Science session at the 2023 annual meeting of the American Academy of Neurology.
On this device, the attenuation of levodopa fluctuations “translated into dramatic improvements in clinical behavior, including highly significant reductions in OFF time and an increase in ON time with no dyskinesias,” reported C. Warren Olanow, MD, who is a chairman emeritus of the department of neurology at the Icahn School of Medicine at Mount Sinai, New York, and now an employee of the company developing this new device.
A novel strategy
Numerous studies have demonstrated that reductions in the troughs of plasma levodopa associated with oral dosing result in longer ON time with fewer dyskinesias, according to Dr. Olanow, who explained this has led to strategies for numerous strategies to achieve continuous delivery. A device that delivers levodopa into the stomach through a surgically implanted catheter has already received regulatory approval. Other devices delivering levodopa subcutaneously are in development, but Dr. Olanow said each of these has had limitations.
“The problem with these approaches is they are associated with potentially serious side effects and they require the patient to wear a cumbersome device,” he explained. Relative to the subcutaneous delivery systems, which have been associated with injection site reactions that include painful nodules, and the surgically implanted devices, which also require an external pump, the latest strategy avoids both disadvantages.
Called DopaFuse, the experimental device is designed to deliver the levodopa and carbidopa into the mouth through a micropump within a wearable retainer. Dr. Olanow said that previous experimental studies demonstrated that small doses of levodopa delivered by mouth to the gastrointestinal system reduce levodopa plasma variability. This early clinical study supports that premise. Levodopa delivered into the mouth by way of a propellant in the retainer-mounted pump improved clinical endpoints.
Encouraging trial results
In the study, 16 patients between the ages of 30 and 75 with Parkinson’s disease were enrolled. On day 1, they received an oral dose of levodopa/carbidopa consistent with their current treatment. On day 2, levodopa/carbidopa was delivered through the retainer-mounted device at equivalent doses. On day 3, they received a single morning oral dose and the received the remainder of their levodopa/carbidopa regimen through the device. On days 4 to 14, they received treatment in the same schedule as day 3.
When pharmacokinetics of levodopa on day 3 were compared with those on day 1, the fluctuation index and coefficient of levodopa concentration variability was reduced to a degree that was highly statistically significant (P < .0001). This, in turn, correlated with “striking” reductions in OFF time with equally statistically significant improvement in ON time and ON time without dyskinesias, according to Dr. Olanow.
Relative to an OFF time of 3.2 hours on day 1, the OFF time of 1.6 hours on day 3 represented a 50% reduction (P < .0001). ON time improved from 12.8 hours to 14.5 hours (P < .001). ON time without dyskinesias improved numerically from 8.8 hours to 9.6 hours.
“There were also improvements in activities of daily living when patients were on DopaFuse, which is a hard endpoint to reach in a study with such a small sample size,” Dr. Olanow reported.
There were no serious adverse events. Three patients reported vomiting and two patients each reported headache, but these events were mild and all resolved within a day. Three patients reported buccal lesions, but these also resolved within a day.
“Some patients reported trouble with speaking in the beginning but at the end of the study, patients were reporting that it was easier to speak because of the motor improvements,” Dr. Olanow said.
Overall, the device was well tolerated by the subjects, providing the evidence for the next stages of clinical studies, reported Dr. Olanow.
“If this turns out to be what we hope it is, it will allow us to deliver levodopa without motor complications, without need for a surgical procedure, and without the risk of subcutaneous lesions,” Dr. Olanow said.
More delivery strategies are needed
This device is in an early phase of development, but several specialists in Parkinson’s disease agreed that there is a need for more strategies to provide continuous levodopa in patients with advancing symptoms. Stuart Isaacson, MD, director, Parkinson’s Disease and Movement Disorders Center of Boca Raton, Fla., is among them.
“Novel delivery devices that can provide more continuous levodopa delivery would be an important therapeutic advance,” Dr. Isaacson said. He called levodopa “the cornerstone of treatment through the course of Parkinson’s disease,” but more physiologic dosing in advancing disease has been a challenge.
“While there are many therapies currently available to manage OFF time, many people living with Parkinson’s disease continue to spend only half of their waking day with good ON time,” he added.
The currently approved method of delivering continuous levodopa through a surgically placed catheter into the gastrointestinal system is effective, but has limitations, according to Aaron L. Ellenbogen, MD, a neurologist at Beaumont Hospital, Farmington Hills, Mich.
“One of the challenges with the current treatment landscape of Parkinson’s disease is that medication can be absorbed variably through the gastrointestinal system,” he said. “As the disease progresses, this often becomes more troublesome.” Although this new device is likely to share this issue, Dr. Ellenbogen said that several devices might be useful to match patients with the one that works best for them.
Dr. Olanow is the founder and CEO of Clintrex Research Corporation, through which he also serves as chief medical officer of SynAgile, the company developing DopaFuse. Dr. Isaacson has financial relationships with more than 30 companies, including those that produce levodopa and levodopa delivery systems. Dr. Ellenbogen has financial relationships with Allergan, Acorda, Supernus, and Teva.
BOSTON – , according to an early clinical experience described in the Emerging Science session at the 2023 annual meeting of the American Academy of Neurology.
On this device, the attenuation of levodopa fluctuations “translated into dramatic improvements in clinical behavior, including highly significant reductions in OFF time and an increase in ON time with no dyskinesias,” reported C. Warren Olanow, MD, who is a chairman emeritus of the department of neurology at the Icahn School of Medicine at Mount Sinai, New York, and now an employee of the company developing this new device.
A novel strategy
Numerous studies have demonstrated that reductions in the troughs of plasma levodopa associated with oral dosing result in longer ON time with fewer dyskinesias, according to Dr. Olanow, who explained this has led to strategies for numerous strategies to achieve continuous delivery. A device that delivers levodopa into the stomach through a surgically implanted catheter has already received regulatory approval. Other devices delivering levodopa subcutaneously are in development, but Dr. Olanow said each of these has had limitations.
“The problem with these approaches is they are associated with potentially serious side effects and they require the patient to wear a cumbersome device,” he explained. Relative to the subcutaneous delivery systems, which have been associated with injection site reactions that include painful nodules, and the surgically implanted devices, which also require an external pump, the latest strategy avoids both disadvantages.
Called DopaFuse, the experimental device is designed to deliver the levodopa and carbidopa into the mouth through a micropump within a wearable retainer. Dr. Olanow said that previous experimental studies demonstrated that small doses of levodopa delivered by mouth to the gastrointestinal system reduce levodopa plasma variability. This early clinical study supports that premise. Levodopa delivered into the mouth by way of a propellant in the retainer-mounted pump improved clinical endpoints.
Encouraging trial results
In the study, 16 patients between the ages of 30 and 75 with Parkinson’s disease were enrolled. On day 1, they received an oral dose of levodopa/carbidopa consistent with their current treatment. On day 2, levodopa/carbidopa was delivered through the retainer-mounted device at equivalent doses. On day 3, they received a single morning oral dose and the received the remainder of their levodopa/carbidopa regimen through the device. On days 4 to 14, they received treatment in the same schedule as day 3.
When pharmacokinetics of levodopa on day 3 were compared with those on day 1, the fluctuation index and coefficient of levodopa concentration variability was reduced to a degree that was highly statistically significant (P < .0001). This, in turn, correlated with “striking” reductions in OFF time with equally statistically significant improvement in ON time and ON time without dyskinesias, according to Dr. Olanow.
Relative to an OFF time of 3.2 hours on day 1, the OFF time of 1.6 hours on day 3 represented a 50% reduction (P < .0001). ON time improved from 12.8 hours to 14.5 hours (P < .001). ON time without dyskinesias improved numerically from 8.8 hours to 9.6 hours.
“There were also improvements in activities of daily living when patients were on DopaFuse, which is a hard endpoint to reach in a study with such a small sample size,” Dr. Olanow reported.
There were no serious adverse events. Three patients reported vomiting and two patients each reported headache, but these events were mild and all resolved within a day. Three patients reported buccal lesions, but these also resolved within a day.
“Some patients reported trouble with speaking in the beginning but at the end of the study, patients were reporting that it was easier to speak because of the motor improvements,” Dr. Olanow said.
Overall, the device was well tolerated by the subjects, providing the evidence for the next stages of clinical studies, reported Dr. Olanow.
“If this turns out to be what we hope it is, it will allow us to deliver levodopa without motor complications, without need for a surgical procedure, and without the risk of subcutaneous lesions,” Dr. Olanow said.
More delivery strategies are needed
This device is in an early phase of development, but several specialists in Parkinson’s disease agreed that there is a need for more strategies to provide continuous levodopa in patients with advancing symptoms. Stuart Isaacson, MD, director, Parkinson’s Disease and Movement Disorders Center of Boca Raton, Fla., is among them.
“Novel delivery devices that can provide more continuous levodopa delivery would be an important therapeutic advance,” Dr. Isaacson said. He called levodopa “the cornerstone of treatment through the course of Parkinson’s disease,” but more physiologic dosing in advancing disease has been a challenge.
“While there are many therapies currently available to manage OFF time, many people living with Parkinson’s disease continue to spend only half of their waking day with good ON time,” he added.
The currently approved method of delivering continuous levodopa through a surgically placed catheter into the gastrointestinal system is effective, but has limitations, according to Aaron L. Ellenbogen, MD, a neurologist at Beaumont Hospital, Farmington Hills, Mich.
“One of the challenges with the current treatment landscape of Parkinson’s disease is that medication can be absorbed variably through the gastrointestinal system,” he said. “As the disease progresses, this often becomes more troublesome.” Although this new device is likely to share this issue, Dr. Ellenbogen said that several devices might be useful to match patients with the one that works best for them.
Dr. Olanow is the founder and CEO of Clintrex Research Corporation, through which he also serves as chief medical officer of SynAgile, the company developing DopaFuse. Dr. Isaacson has financial relationships with more than 30 companies, including those that produce levodopa and levodopa delivery systems. Dr. Ellenbogen has financial relationships with Allergan, Acorda, Supernus, and Teva.
FROM AAN 2023
Survey reveals room for improvement in teen substance use screening
WASHINGTON – , Deepa Camenga, MD, said in a presentation at the 2023 Pediatric Academic Societies annual meeting.
The American Academy of Pediatrics recommends universal screening for substance use in adolescents during annual health visits, but current screening rates and practices among primary care pediatricians in the United States are unknown, said Dr. Camenga, an associate professor at Yale University, New Haven, Conn.
Uniformity in screening is lacking
Dr. Camenga presented data from the 2021 AAP Periodic Survey, which included 1,683 nonretired AAP members in the United States. Residents were excluded. The current analysis included 471 pediatricians who reported providing health supervision to adolescents. Overall, 284 of the 471 included respondents (60%) reported always screening adolescent patients for substance use during a health supervision visit. Of these, 42% reported using a standardized screening instrument, Dr. Camenga said.
The majority (70%) of pediatricians who used a standardized screening tool opted for the CRAFFT tool (Car, Relax, Alone, Forget, Friends, Trouble) designed for ages 12-21 years. Another 21% reported using an unspecified screening tool, 4% used RAAPS (Rapid Assessment for Adolescent Preventive Services), 3% used S2BI (Screening to Brief Intervention), and 1% used BSTAD (Brief Screener for Tobacco, Alcohol, and other Drugs).
A total of 77% of respondents reported screening their adolescent patients for substance use without a parent or guardian present. Approximately half (52%) used paper-based screening, 22% used electronic screening, 21% used verbal screening, and 6% reported other methods.
A total of 68% and 70% of respondents, respectively, agreed or strongly agreed that top barriers to screening were the lack of an onsite provider for counseling and the lack of readily available treatment options. Other reported barriers included lack of knowledge or information, patient reluctance to discuss substance use, too many other priorities during the visit, and inadequate payment. Only 6% of respondents strongly agreed that lack of time was a barrier, said Dr. Camenga.
Screening frequency and screening practices varied by geographic region, Dr. Camenga said. Pediatricians in the South and Midwest were only half as likely as those in the Northeast to report always screening adolescents for substance use (adjusted odds ratio, 0.43 and 0.53, respectively; P < .05). Similarly, compared with pediatricians in the Northeast, those in the South, Midwest, and West were significantly less likely to report using a standardized instrument for substance use screening (aOR, 0.53, 0.24, and 0.52, respectively; P < 0.001 for all).
The disparities in screening by geographic region show that there is room for improvement in this area, said Dr. Camenga. Systems-level interventions such as treatment financing and access to telehealth services could improve primary care access to substance use treatment professionals, she said.
At the practice level, embedding screening and referral tools into electronic health records could potentially improve screening rates. Many primary care pediatricians do not receive training in identifying and assessing substance use in their patients, or in first-line treatment, Dr. Camenga said.
“We have to invest in a ‘train the trainer’ type of model,” she emphasized.
Data highlight regional resource gaps
The current study is important because it highlights potential missed opportunities to screen adolescents for substance use, said Sarah Yale, MD, assistant professor of pediatrics at the Medical College of Wisconsin, Milwaukee, in an interview. Dr. Yale said that the disparities in screening by region are interesting and should serve as a focus for resource investment because the lack of specialists for referral and treatment options in these areas is likely a contributing factor.
However, lack of training also plays a role, said Dr. Yale, who was not involved in the study but served as a moderator of the presentation session at the meeting. Many pediatricians in practice have not been trained in substance use screening, and the fact that many of those who did try to screen were not using a standardized screening tool indicates a need for provider education, she said. The take-home message for clinicians is to find ways to include substance use screening in the care of their adolescent patients. Additionally, more research is needed to assess how best to integrate screening tools into visits, whether on paper, electronically, or verbally, and to include training on substance use screening during pediatric medical training.
The survey was conducted by the American Academy of Pediatrics Research Division. This year’s survey was supported by the Conrad N. Hilton Foundation. Dr. Camenga had no financial conflicts to disclose. Dr. Yale had no financial conflicts to disclose.
WASHINGTON – , Deepa Camenga, MD, said in a presentation at the 2023 Pediatric Academic Societies annual meeting.
The American Academy of Pediatrics recommends universal screening for substance use in adolescents during annual health visits, but current screening rates and practices among primary care pediatricians in the United States are unknown, said Dr. Camenga, an associate professor at Yale University, New Haven, Conn.
Uniformity in screening is lacking
Dr. Camenga presented data from the 2021 AAP Periodic Survey, which included 1,683 nonretired AAP members in the United States. Residents were excluded. The current analysis included 471 pediatricians who reported providing health supervision to adolescents. Overall, 284 of the 471 included respondents (60%) reported always screening adolescent patients for substance use during a health supervision visit. Of these, 42% reported using a standardized screening instrument, Dr. Camenga said.
The majority (70%) of pediatricians who used a standardized screening tool opted for the CRAFFT tool (Car, Relax, Alone, Forget, Friends, Trouble) designed for ages 12-21 years. Another 21% reported using an unspecified screening tool, 4% used RAAPS (Rapid Assessment for Adolescent Preventive Services), 3% used S2BI (Screening to Brief Intervention), and 1% used BSTAD (Brief Screener for Tobacco, Alcohol, and other Drugs).
A total of 77% of respondents reported screening their adolescent patients for substance use without a parent or guardian present. Approximately half (52%) used paper-based screening, 22% used electronic screening, 21% used verbal screening, and 6% reported other methods.
A total of 68% and 70% of respondents, respectively, agreed or strongly agreed that top barriers to screening were the lack of an onsite provider for counseling and the lack of readily available treatment options. Other reported barriers included lack of knowledge or information, patient reluctance to discuss substance use, too many other priorities during the visit, and inadequate payment. Only 6% of respondents strongly agreed that lack of time was a barrier, said Dr. Camenga.
Screening frequency and screening practices varied by geographic region, Dr. Camenga said. Pediatricians in the South and Midwest were only half as likely as those in the Northeast to report always screening adolescents for substance use (adjusted odds ratio, 0.43 and 0.53, respectively; P < .05). Similarly, compared with pediatricians in the Northeast, those in the South, Midwest, and West were significantly less likely to report using a standardized instrument for substance use screening (aOR, 0.53, 0.24, and 0.52, respectively; P < 0.001 for all).
The disparities in screening by geographic region show that there is room for improvement in this area, said Dr. Camenga. Systems-level interventions such as treatment financing and access to telehealth services could improve primary care access to substance use treatment professionals, she said.
At the practice level, embedding screening and referral tools into electronic health records could potentially improve screening rates. Many primary care pediatricians do not receive training in identifying and assessing substance use in their patients, or in first-line treatment, Dr. Camenga said.
“We have to invest in a ‘train the trainer’ type of model,” she emphasized.
Data highlight regional resource gaps
The current study is important because it highlights potential missed opportunities to screen adolescents for substance use, said Sarah Yale, MD, assistant professor of pediatrics at the Medical College of Wisconsin, Milwaukee, in an interview. Dr. Yale said that the disparities in screening by region are interesting and should serve as a focus for resource investment because the lack of specialists for referral and treatment options in these areas is likely a contributing factor.
However, lack of training also plays a role, said Dr. Yale, who was not involved in the study but served as a moderator of the presentation session at the meeting. Many pediatricians in practice have not been trained in substance use screening, and the fact that many of those who did try to screen were not using a standardized screening tool indicates a need for provider education, she said. The take-home message for clinicians is to find ways to include substance use screening in the care of their adolescent patients. Additionally, more research is needed to assess how best to integrate screening tools into visits, whether on paper, electronically, or verbally, and to include training on substance use screening during pediatric medical training.
The survey was conducted by the American Academy of Pediatrics Research Division. This year’s survey was supported by the Conrad N. Hilton Foundation. Dr. Camenga had no financial conflicts to disclose. Dr. Yale had no financial conflicts to disclose.
WASHINGTON – , Deepa Camenga, MD, said in a presentation at the 2023 Pediatric Academic Societies annual meeting.
The American Academy of Pediatrics recommends universal screening for substance use in adolescents during annual health visits, but current screening rates and practices among primary care pediatricians in the United States are unknown, said Dr. Camenga, an associate professor at Yale University, New Haven, Conn.
Uniformity in screening is lacking
Dr. Camenga presented data from the 2021 AAP Periodic Survey, which included 1,683 nonretired AAP members in the United States. Residents were excluded. The current analysis included 471 pediatricians who reported providing health supervision to adolescents. Overall, 284 of the 471 included respondents (60%) reported always screening adolescent patients for substance use during a health supervision visit. Of these, 42% reported using a standardized screening instrument, Dr. Camenga said.
The majority (70%) of pediatricians who used a standardized screening tool opted for the CRAFFT tool (Car, Relax, Alone, Forget, Friends, Trouble) designed for ages 12-21 years. Another 21% reported using an unspecified screening tool, 4% used RAAPS (Rapid Assessment for Adolescent Preventive Services), 3% used S2BI (Screening to Brief Intervention), and 1% used BSTAD (Brief Screener for Tobacco, Alcohol, and other Drugs).
A total of 77% of respondents reported screening their adolescent patients for substance use without a parent or guardian present. Approximately half (52%) used paper-based screening, 22% used electronic screening, 21% used verbal screening, and 6% reported other methods.
A total of 68% and 70% of respondents, respectively, agreed or strongly agreed that top barriers to screening were the lack of an onsite provider for counseling and the lack of readily available treatment options. Other reported barriers included lack of knowledge or information, patient reluctance to discuss substance use, too many other priorities during the visit, and inadequate payment. Only 6% of respondents strongly agreed that lack of time was a barrier, said Dr. Camenga.
Screening frequency and screening practices varied by geographic region, Dr. Camenga said. Pediatricians in the South and Midwest were only half as likely as those in the Northeast to report always screening adolescents for substance use (adjusted odds ratio, 0.43 and 0.53, respectively; P < .05). Similarly, compared with pediatricians in the Northeast, those in the South, Midwest, and West were significantly less likely to report using a standardized instrument for substance use screening (aOR, 0.53, 0.24, and 0.52, respectively; P < 0.001 for all).
The disparities in screening by geographic region show that there is room for improvement in this area, said Dr. Camenga. Systems-level interventions such as treatment financing and access to telehealth services could improve primary care access to substance use treatment professionals, she said.
At the practice level, embedding screening and referral tools into electronic health records could potentially improve screening rates. Many primary care pediatricians do not receive training in identifying and assessing substance use in their patients, or in first-line treatment, Dr. Camenga said.
“We have to invest in a ‘train the trainer’ type of model,” she emphasized.
Data highlight regional resource gaps
The current study is important because it highlights potential missed opportunities to screen adolescents for substance use, said Sarah Yale, MD, assistant professor of pediatrics at the Medical College of Wisconsin, Milwaukee, in an interview. Dr. Yale said that the disparities in screening by region are interesting and should serve as a focus for resource investment because the lack of specialists for referral and treatment options in these areas is likely a contributing factor.
However, lack of training also plays a role, said Dr. Yale, who was not involved in the study but served as a moderator of the presentation session at the meeting. Many pediatricians in practice have not been trained in substance use screening, and the fact that many of those who did try to screen were not using a standardized screening tool indicates a need for provider education, she said. The take-home message for clinicians is to find ways to include substance use screening in the care of their adolescent patients. Additionally, more research is needed to assess how best to integrate screening tools into visits, whether on paper, electronically, or verbally, and to include training on substance use screening during pediatric medical training.
The survey was conducted by the American Academy of Pediatrics Research Division. This year’s survey was supported by the Conrad N. Hilton Foundation. Dr. Camenga had no financial conflicts to disclose. Dr. Yale had no financial conflicts to disclose.
AT PAS 2023
Active older women show heightened AFib risk
Older women with high levels of physical activity showed twice the risk of atrial fibrillation (AFib) over 10 years as they did for cardiac disease or stroke, based on data from 46 cross-country skiers.
Although previous research suggests that women derive greater health benefits from endurance sports, compared with men, women are generally underrepresented in sports cardiology research, and most previous studies have focused on younger women, Marius Myrstad, MD, of Baerum Hospital, Gjettum, Norway, said in a presentation at the annual congress of the European Association of Preventive Cardiology.
Previous research also has shown an increased risk of AFib in male endurance athletes, but similar data on women are lacking, Dr. Myrstad said.
The researchers reviewed data from the Birkebeiner Ageing Study, a study of Norwegian cross-country skiers aged 65 years and older who were followed for 10 years. The participants were competitors in the 2009/2010 Birkebeiner race, a 54-km cross country ski race in Norway.
Participants responded to a questionnaire addressing cardiovascular disease risk factors, exercise habits, and other health issues. The mean age at baseline was 67.5 year. A total of 34 participants (76%) were available for follow-up visits in 2014, and 36 attended a follow-up visit in 2020. Cumulative exposure to exercise was 26 years.
A total of 86% of the women reported moderate to vigorous exercise in the past year at baseline; 61% did so at the 2020 follow-up visit. One of the participants died during the study period.
“The baseline prevalence of cardiovascular conditions was very low,” Dr. Myrstad noted.
However, despite a low prevalence of cardiovascular risk factors, the risk of AFib in the study population was twice as high as for other cardiac diseases and stroke (15.6%, 7.1%, and 7.1%, respectively).
The mechanism of action for the increased AFib remains unclear, but the current study highlights the need for large, prospective studies of female athletes to address not only AFib, but also exercise-induced cardiac remodeling and cardiovascular health in general, said Dr. Myrstad.
The findings were limited by the small sample size and use of self-reports, Dr. Myrstad said, and more research is needed to clarify the association between increased AFib and high-level athletic activity in women.
“We should strive to close the gap between female and male athletes in sports cardiology research,” he added.
Consider the big picture of AFib risk
This study is important because of the growing recognition that atrial fibrillation may be a preventable disease, said Gregory Marcus, MD, a cardiologist at the University of California, San Francisco, said in an interview.
“Various behaviors or exposures that are under the control of the individual patient may reveal especially powerful means to help reduce risk,” he added.
Dr. Marcus said he was not surprised by the current study findings, as they reflect those of other studies suggesting a heightened risk for atrial fibrillation associated with very excessive exercise. However, the study was limited by the relatively small size and lack of a comparison group, he said. In addition, “The study was observational, and therefore the possibility that factors other than the predictor of interest, in this case intensive endurance exercise, were truly causal of atrial fibrillation could not be excluded,” he noted.
“It is very important to place this specialized analysis in the greater context of the full weight of evidence related to physical activity and atrial fibrillation,” said Dr. Marcus. “Specifically, when it comes to the general public and the great majority of patients we see in clinical practice, encouraging more physical activity is generally the best approach to reduce risks of atrial fibrillation,” he said. “It appears to be only in extraordinarily rigorous and prolonged endurance exercise that higher risks of atrial fibrillation may result,” he noted.
However, “Exercise also has many other benefits, related to overall cardiovascular health, brain health, bone health, and even cancer risk reduction, such that, even among the highly trained endurance athletes, the net benefit versus risk remains unknown,” he said.
“While the risk of atrial fibrillation in these highly trained endurance athletes was higher than expected, it still occurred in the minority,” Dr. Marcus said. “Therefore, there are certainly other factors yet to be identified that influence this heightened atrial fibrillation risk, and future research aimed at elucidating these other factors may help identify individuals more or less prone to atrial fibrillation or other behaviors that can help mitigate that risk.”
Dr. Myrstad disclosed lecture fees from Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, MSD, and Pfizer unrelated to the current study. Dr. Marcus disclosed serving as a consultant for Johnson and Johnson and InCarda, and holding equity as a cofounder of InCarda.
Older women with high levels of physical activity showed twice the risk of atrial fibrillation (AFib) over 10 years as they did for cardiac disease or stroke, based on data from 46 cross-country skiers.
Although previous research suggests that women derive greater health benefits from endurance sports, compared with men, women are generally underrepresented in sports cardiology research, and most previous studies have focused on younger women, Marius Myrstad, MD, of Baerum Hospital, Gjettum, Norway, said in a presentation at the annual congress of the European Association of Preventive Cardiology.
Previous research also has shown an increased risk of AFib in male endurance athletes, but similar data on women are lacking, Dr. Myrstad said.
The researchers reviewed data from the Birkebeiner Ageing Study, a study of Norwegian cross-country skiers aged 65 years and older who were followed for 10 years. The participants were competitors in the 2009/2010 Birkebeiner race, a 54-km cross country ski race in Norway.
Participants responded to a questionnaire addressing cardiovascular disease risk factors, exercise habits, and other health issues. The mean age at baseline was 67.5 year. A total of 34 participants (76%) were available for follow-up visits in 2014, and 36 attended a follow-up visit in 2020. Cumulative exposure to exercise was 26 years.
A total of 86% of the women reported moderate to vigorous exercise in the past year at baseline; 61% did so at the 2020 follow-up visit. One of the participants died during the study period.
“The baseline prevalence of cardiovascular conditions was very low,” Dr. Myrstad noted.
However, despite a low prevalence of cardiovascular risk factors, the risk of AFib in the study population was twice as high as for other cardiac diseases and stroke (15.6%, 7.1%, and 7.1%, respectively).
The mechanism of action for the increased AFib remains unclear, but the current study highlights the need for large, prospective studies of female athletes to address not only AFib, but also exercise-induced cardiac remodeling and cardiovascular health in general, said Dr. Myrstad.
The findings were limited by the small sample size and use of self-reports, Dr. Myrstad said, and more research is needed to clarify the association between increased AFib and high-level athletic activity in women.
“We should strive to close the gap between female and male athletes in sports cardiology research,” he added.
Consider the big picture of AFib risk
This study is important because of the growing recognition that atrial fibrillation may be a preventable disease, said Gregory Marcus, MD, a cardiologist at the University of California, San Francisco, said in an interview.
“Various behaviors or exposures that are under the control of the individual patient may reveal especially powerful means to help reduce risk,” he added.
Dr. Marcus said he was not surprised by the current study findings, as they reflect those of other studies suggesting a heightened risk for atrial fibrillation associated with very excessive exercise. However, the study was limited by the relatively small size and lack of a comparison group, he said. In addition, “The study was observational, and therefore the possibility that factors other than the predictor of interest, in this case intensive endurance exercise, were truly causal of atrial fibrillation could not be excluded,” he noted.
“It is very important to place this specialized analysis in the greater context of the full weight of evidence related to physical activity and atrial fibrillation,” said Dr. Marcus. “Specifically, when it comes to the general public and the great majority of patients we see in clinical practice, encouraging more physical activity is generally the best approach to reduce risks of atrial fibrillation,” he said. “It appears to be only in extraordinarily rigorous and prolonged endurance exercise that higher risks of atrial fibrillation may result,” he noted.
However, “Exercise also has many other benefits, related to overall cardiovascular health, brain health, bone health, and even cancer risk reduction, such that, even among the highly trained endurance athletes, the net benefit versus risk remains unknown,” he said.
“While the risk of atrial fibrillation in these highly trained endurance athletes was higher than expected, it still occurred in the minority,” Dr. Marcus said. “Therefore, there are certainly other factors yet to be identified that influence this heightened atrial fibrillation risk, and future research aimed at elucidating these other factors may help identify individuals more or less prone to atrial fibrillation or other behaviors that can help mitigate that risk.”
Dr. Myrstad disclosed lecture fees from Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, MSD, and Pfizer unrelated to the current study. Dr. Marcus disclosed serving as a consultant for Johnson and Johnson and InCarda, and holding equity as a cofounder of InCarda.
Older women with high levels of physical activity showed twice the risk of atrial fibrillation (AFib) over 10 years as they did for cardiac disease or stroke, based on data from 46 cross-country skiers.
Although previous research suggests that women derive greater health benefits from endurance sports, compared with men, women are generally underrepresented in sports cardiology research, and most previous studies have focused on younger women, Marius Myrstad, MD, of Baerum Hospital, Gjettum, Norway, said in a presentation at the annual congress of the European Association of Preventive Cardiology.
Previous research also has shown an increased risk of AFib in male endurance athletes, but similar data on women are lacking, Dr. Myrstad said.
The researchers reviewed data from the Birkebeiner Ageing Study, a study of Norwegian cross-country skiers aged 65 years and older who were followed for 10 years. The participants were competitors in the 2009/2010 Birkebeiner race, a 54-km cross country ski race in Norway.
Participants responded to a questionnaire addressing cardiovascular disease risk factors, exercise habits, and other health issues. The mean age at baseline was 67.5 year. A total of 34 participants (76%) were available for follow-up visits in 2014, and 36 attended a follow-up visit in 2020. Cumulative exposure to exercise was 26 years.
A total of 86% of the women reported moderate to vigorous exercise in the past year at baseline; 61% did so at the 2020 follow-up visit. One of the participants died during the study period.
“The baseline prevalence of cardiovascular conditions was very low,” Dr. Myrstad noted.
However, despite a low prevalence of cardiovascular risk factors, the risk of AFib in the study population was twice as high as for other cardiac diseases and stroke (15.6%, 7.1%, and 7.1%, respectively).
The mechanism of action for the increased AFib remains unclear, but the current study highlights the need for large, prospective studies of female athletes to address not only AFib, but also exercise-induced cardiac remodeling and cardiovascular health in general, said Dr. Myrstad.
The findings were limited by the small sample size and use of self-reports, Dr. Myrstad said, and more research is needed to clarify the association between increased AFib and high-level athletic activity in women.
“We should strive to close the gap between female and male athletes in sports cardiology research,” he added.
Consider the big picture of AFib risk
This study is important because of the growing recognition that atrial fibrillation may be a preventable disease, said Gregory Marcus, MD, a cardiologist at the University of California, San Francisco, said in an interview.
“Various behaviors or exposures that are under the control of the individual patient may reveal especially powerful means to help reduce risk,” he added.
Dr. Marcus said he was not surprised by the current study findings, as they reflect those of other studies suggesting a heightened risk for atrial fibrillation associated with very excessive exercise. However, the study was limited by the relatively small size and lack of a comparison group, he said. In addition, “The study was observational, and therefore the possibility that factors other than the predictor of interest, in this case intensive endurance exercise, were truly causal of atrial fibrillation could not be excluded,” he noted.
“It is very important to place this specialized analysis in the greater context of the full weight of evidence related to physical activity and atrial fibrillation,” said Dr. Marcus. “Specifically, when it comes to the general public and the great majority of patients we see in clinical practice, encouraging more physical activity is generally the best approach to reduce risks of atrial fibrillation,” he said. “It appears to be only in extraordinarily rigorous and prolonged endurance exercise that higher risks of atrial fibrillation may result,” he noted.
However, “Exercise also has many other benefits, related to overall cardiovascular health, brain health, bone health, and even cancer risk reduction, such that, even among the highly trained endurance athletes, the net benefit versus risk remains unknown,” he said.
“While the risk of atrial fibrillation in these highly trained endurance athletes was higher than expected, it still occurred in the minority,” Dr. Marcus said. “Therefore, there are certainly other factors yet to be identified that influence this heightened atrial fibrillation risk, and future research aimed at elucidating these other factors may help identify individuals more or less prone to atrial fibrillation or other behaviors that can help mitigate that risk.”
Dr. Myrstad disclosed lecture fees from Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, MSD, and Pfizer unrelated to the current study. Dr. Marcus disclosed serving as a consultant for Johnson and Johnson and InCarda, and holding equity as a cofounder of InCarda.
FROM ESC PREVENTIVE CARDIOLOGY 2023
Best practices document outlines genitourinary applications of lasers and energy-based devices
PHOENIX –
“Even a cursory review of PubMed today yields over 100,000 results” on this topic, Macrene R. Alexiades, MD, PhD, associate clinical professor of dermatology at Yale University, New Haven, Conn., said at the annual conference of the American Society for Laser Medicine and Surgery. “Add to that radiofrequency and various diagnoses, the number of publications has skyrocketed, particularly over the last 10 years.”
What has been missing from this hot research topic all these years, she continued, is that no one has distilled this pile of data into a practical guide for office-based clinicians who use lasers and energy-based devices for genitourinary conditions – until now. Working with experts in gynecology and urogynecology, Dr. Alexiades spearheaded a 2-year-long effort to assemble a document on optimal protocols and best practices for genitourinary application of lasers and energy-based devices. The document, published soon after the ASLMS meeting in Lasers in Medicine and Surgery, includes a table that lists the current Food and Drug Administration approval status of devices in genitourinary applications, as well as individual sections dedicated to fractional lasers, radiofrequency (RF) devices, and high-intensity focused electromagnetic technology. It concludes with a section on the current status of clearances and future pathways.
“The work we did was exhaustive,” said Dr. Alexiades, who is also founder and director of Dermatology & Laser Surgery Center of New York. “We went through all the clinical trial data and compiled the parameters that, as a consensus, we agree are best practices for each technology for which we had rigorous published data.”
The document contains a brief background on the history of the devices used for genitourinary issues and it addresses core topics for each technology, such as conditions treated, contraindications, preoperative physical assessment and preparation, perioperative protocols, and postoperative care.
Contraindications to the genitourinary use of lasers and energy-based devices are numerous and include use of an intrauterine device, active urinary tract or genital infection, vaginal bleeding, current pregnancy, active or recent malignancy, having an electrical implant anywhere in the body, significant concurrent illness, and an anticoagulative or thromboembolic condition or taking anticoagulant medications 1 week prior to the procedure. Another condition to screen for is advanced prolapse, which was considered a contraindication in all clinical trials, she added. “It’s important that you’re able to do the speculum exam and stage the prolapse” so that a patient with this contraindication is not treated.
Dr. Alexiades shared the following highlights from the document’s section related to the use of fractional CO2 lasers:
Preoperative management. Schedule the treatment one week after the patient’s menstrual period. Patients should avoid blood thinners for 7 days and avoid intercourse the night before the procedure. Reschedule in the case of fever, chills, or vaginal bleeding or discharge.
Preoperative physical exam and testing. A normal speculum exam and a recent negative PAP smear are required. For those of child-bearing potential, a pregnancy test is warranted. Obtain written and verbal consent, including discussion of all treatment options, risks, and benefits. No topical or local anesthesia is necessary internally. “Externally, we sometimes apply topical lidocaine gel, but I have found that’s not necessary in most cases,” Dr. Alexiades said. “The treatment is so quick.”
Peri-operative management. In general, device settings are provided by the manufacturer. “For most of the studies that had successful outcomes and no adverse events, researchers adhered to the mild or moderate settings on the technology,” she said. Energy settings were between 15 and 30 watts, delivered at a laser fluence of about 250-300 mJ/cm2 with a spacing of microbeams 1 mm apart. Typically, three treatments are done at 1-month intervals and maintenance treatments are recommended at 6 and 12 months based on duration of the outcomes.
Vulvovaginal postoperative management. A 3-day recovery time is recommended with avoidance of intercourse during this period, because “re-epithelialization is usually complete in 3 days, so we want to give the opportunity for the lining to heal prior to introducing any friction, Dr. Alexiades said.” Rarely, spotting or discharge may occur and there should be no discomfort. “Any severe discomfort or burning may potentially signify infection and should prompt evaluation and possibly vaginal cultures. The patient can shower, but we recommend avoiding seated baths to decrease any introduction of infectious agents.”
Patients should be followed up monthly until three treatments are completed, and a maintenance treatment is considered appropriate between 6 and 12 months. “I do recommend doing a 1-month follow-up following the final treatment, unless it’s a patient who has already had a series of three treatments and is coming in for maintenance,” she said.
In a study from her own practice, Dr. Alexiades evaluated a series of three fractional CO2 laser treatments to the vulva and vagina with a 1-year follow-up in postmenopausal patients. She used the Vaginal Health Index (VHI) to assess changes in vaginal elasticity, fluid volume, vaginal pH, epithelial integrity, and moisture. She and her colleagues discovered that there was improvement in every VHI category after treatment and during the follow-up interval up to 6 months.
“Between 6 and 12 months, we started to see a return a bit toward baseline on all of these parameters,” she said. “The serendipitous discovery that I made during the course of that study was that early intervention improves outcomes. I observed that the younger, most recently postmenopausal cohort seemed to attain normal or near normal VHI quicker than the more extended postmenopausal cohorts.”
In an editorial published in 2020, Dr. Alexiades reviewed the effects of fractional CO2 laser treatment of vulvar skin on vaginal pH and referred to a study she conducted that found that the mean baseline pH pretreatment was 6.32 in the cohort of postmenopausal patients, and was reduced after 3 treatments. “Postmenopausally, the normal acidic pH becomes alkaline,” she said. But she did not expect to see an additional reduction in pH following the treatment out to 6 months. “This indicates that, whatever the wound healing and other restorative effects of these devices are, they seem to continue out to 6 months, at which point it turns around and moves toward baseline [levels].”
Dr. Alexiades highlighted two published meta-analyses of studies related to the genitourinary use of lasers and energy-based devices. One included 59 studies of 3,609 women treated for vaginal rejuvenation using either radiofrequency or fractional ablative laser therapy. The studies reported improvements in symptoms of GSM/VVA and sexual function, high patient satisfaction, with minor adverse events, including treatment-associated vaginal swelling or vaginal discharge.
“Further research needs to be completed to determine which specific pathologies can be treated, if maintenance treatment is necessary, and long-term safety concerns,” the authors concluded.
In another review, researchers analyzed 64 studies related to vaginal laser therapy for GSM. Of these, 47 were before and after studies without a control group, 10 were controlled intervention studies, and 7 were observational cohort and cross-sectional studies.
Vaginal laser treatment “seems to improve scores on the visual analogue scale, Female Sexual Function Index, and the Vaginal Health Index over the short term,” the authors wrote. “Safety outcomes are underreported and short term. Further well-designed clinical trials with sham-laser control groups and evaluating objective variables are needed to provide the best evidence on efficacy.”
“Lasers and energy-based devices are now considered alternative therapeutic modalities for genitourinary conditions,” Dr. Alexiades concluded. “The shortcomings in the literature with respect to lasers and device treatments demonstrate the need for the consensus on best practices and protocols.”
During a separate presentation at the meeting, Michael Gold, MD, highlighted data from Grand View Research, a market research database, which estimated that the global women’s health and wellness market is valued at more than $31 billion globally and is expected to grow at a compound annual growth rate of 4.8% from 2022 to 2030.
“Sales of women’s health energy-based devices continue to grow as new technologies are developed,” said Dr. Gold, a Nashville, Tenn.–based dermatologist and cosmetic surgeon who is also editor-in-chief of the Journal of Cosmetic Dermatology. “Evolving societal norms have made discussions about feminine health issues acceptable. Suffering in silence is no longer necessary or advocated.”
Dr. Alexiades disclosed that she has conducted research for Candela Lasers, Lumenis, Allergan/AbbVie, InMode, and Endymed. She is also the founder and CEO of Macrene Actives. Dr. Gold disclosed that he is a consultant to and/or an investigator and a speaker for Joylux, InMode, and Alma Lasers.
PHOENIX –
“Even a cursory review of PubMed today yields over 100,000 results” on this topic, Macrene R. Alexiades, MD, PhD, associate clinical professor of dermatology at Yale University, New Haven, Conn., said at the annual conference of the American Society for Laser Medicine and Surgery. “Add to that radiofrequency and various diagnoses, the number of publications has skyrocketed, particularly over the last 10 years.”
What has been missing from this hot research topic all these years, she continued, is that no one has distilled this pile of data into a practical guide for office-based clinicians who use lasers and energy-based devices for genitourinary conditions – until now. Working with experts in gynecology and urogynecology, Dr. Alexiades spearheaded a 2-year-long effort to assemble a document on optimal protocols and best practices for genitourinary application of lasers and energy-based devices. The document, published soon after the ASLMS meeting in Lasers in Medicine and Surgery, includes a table that lists the current Food and Drug Administration approval status of devices in genitourinary applications, as well as individual sections dedicated to fractional lasers, radiofrequency (RF) devices, and high-intensity focused electromagnetic technology. It concludes with a section on the current status of clearances and future pathways.
“The work we did was exhaustive,” said Dr. Alexiades, who is also founder and director of Dermatology & Laser Surgery Center of New York. “We went through all the clinical trial data and compiled the parameters that, as a consensus, we agree are best practices for each technology for which we had rigorous published data.”
The document contains a brief background on the history of the devices used for genitourinary issues and it addresses core topics for each technology, such as conditions treated, contraindications, preoperative physical assessment and preparation, perioperative protocols, and postoperative care.
Contraindications to the genitourinary use of lasers and energy-based devices are numerous and include use of an intrauterine device, active urinary tract or genital infection, vaginal bleeding, current pregnancy, active or recent malignancy, having an electrical implant anywhere in the body, significant concurrent illness, and an anticoagulative or thromboembolic condition or taking anticoagulant medications 1 week prior to the procedure. Another condition to screen for is advanced prolapse, which was considered a contraindication in all clinical trials, she added. “It’s important that you’re able to do the speculum exam and stage the prolapse” so that a patient with this contraindication is not treated.
Dr. Alexiades shared the following highlights from the document’s section related to the use of fractional CO2 lasers:
Preoperative management. Schedule the treatment one week after the patient’s menstrual period. Patients should avoid blood thinners for 7 days and avoid intercourse the night before the procedure. Reschedule in the case of fever, chills, or vaginal bleeding or discharge.
Preoperative physical exam and testing. A normal speculum exam and a recent negative PAP smear are required. For those of child-bearing potential, a pregnancy test is warranted. Obtain written and verbal consent, including discussion of all treatment options, risks, and benefits. No topical or local anesthesia is necessary internally. “Externally, we sometimes apply topical lidocaine gel, but I have found that’s not necessary in most cases,” Dr. Alexiades said. “The treatment is so quick.”
Peri-operative management. In general, device settings are provided by the manufacturer. “For most of the studies that had successful outcomes and no adverse events, researchers adhered to the mild or moderate settings on the technology,” she said. Energy settings were between 15 and 30 watts, delivered at a laser fluence of about 250-300 mJ/cm2 with a spacing of microbeams 1 mm apart. Typically, three treatments are done at 1-month intervals and maintenance treatments are recommended at 6 and 12 months based on duration of the outcomes.
Vulvovaginal postoperative management. A 3-day recovery time is recommended with avoidance of intercourse during this period, because “re-epithelialization is usually complete in 3 days, so we want to give the opportunity for the lining to heal prior to introducing any friction, Dr. Alexiades said.” Rarely, spotting or discharge may occur and there should be no discomfort. “Any severe discomfort or burning may potentially signify infection and should prompt evaluation and possibly vaginal cultures. The patient can shower, but we recommend avoiding seated baths to decrease any introduction of infectious agents.”
Patients should be followed up monthly until three treatments are completed, and a maintenance treatment is considered appropriate between 6 and 12 months. “I do recommend doing a 1-month follow-up following the final treatment, unless it’s a patient who has already had a series of three treatments and is coming in for maintenance,” she said.
In a study from her own practice, Dr. Alexiades evaluated a series of three fractional CO2 laser treatments to the vulva and vagina with a 1-year follow-up in postmenopausal patients. She used the Vaginal Health Index (VHI) to assess changes in vaginal elasticity, fluid volume, vaginal pH, epithelial integrity, and moisture. She and her colleagues discovered that there was improvement in every VHI category after treatment and during the follow-up interval up to 6 months.
“Between 6 and 12 months, we started to see a return a bit toward baseline on all of these parameters,” she said. “The serendipitous discovery that I made during the course of that study was that early intervention improves outcomes. I observed that the younger, most recently postmenopausal cohort seemed to attain normal or near normal VHI quicker than the more extended postmenopausal cohorts.”
In an editorial published in 2020, Dr. Alexiades reviewed the effects of fractional CO2 laser treatment of vulvar skin on vaginal pH and referred to a study she conducted that found that the mean baseline pH pretreatment was 6.32 in the cohort of postmenopausal patients, and was reduced after 3 treatments. “Postmenopausally, the normal acidic pH becomes alkaline,” she said. But she did not expect to see an additional reduction in pH following the treatment out to 6 months. “This indicates that, whatever the wound healing and other restorative effects of these devices are, they seem to continue out to 6 months, at which point it turns around and moves toward baseline [levels].”
Dr. Alexiades highlighted two published meta-analyses of studies related to the genitourinary use of lasers and energy-based devices. One included 59 studies of 3,609 women treated for vaginal rejuvenation using either radiofrequency or fractional ablative laser therapy. The studies reported improvements in symptoms of GSM/VVA and sexual function, high patient satisfaction, with minor adverse events, including treatment-associated vaginal swelling or vaginal discharge.
“Further research needs to be completed to determine which specific pathologies can be treated, if maintenance treatment is necessary, and long-term safety concerns,” the authors concluded.
In another review, researchers analyzed 64 studies related to vaginal laser therapy for GSM. Of these, 47 were before and after studies without a control group, 10 were controlled intervention studies, and 7 were observational cohort and cross-sectional studies.
Vaginal laser treatment “seems to improve scores on the visual analogue scale, Female Sexual Function Index, and the Vaginal Health Index over the short term,” the authors wrote. “Safety outcomes are underreported and short term. Further well-designed clinical trials with sham-laser control groups and evaluating objective variables are needed to provide the best evidence on efficacy.”
“Lasers and energy-based devices are now considered alternative therapeutic modalities for genitourinary conditions,” Dr. Alexiades concluded. “The shortcomings in the literature with respect to lasers and device treatments demonstrate the need for the consensus on best practices and protocols.”
During a separate presentation at the meeting, Michael Gold, MD, highlighted data from Grand View Research, a market research database, which estimated that the global women’s health and wellness market is valued at more than $31 billion globally and is expected to grow at a compound annual growth rate of 4.8% from 2022 to 2030.
“Sales of women’s health energy-based devices continue to grow as new technologies are developed,” said Dr. Gold, a Nashville, Tenn.–based dermatologist and cosmetic surgeon who is also editor-in-chief of the Journal of Cosmetic Dermatology. “Evolving societal norms have made discussions about feminine health issues acceptable. Suffering in silence is no longer necessary or advocated.”
Dr. Alexiades disclosed that she has conducted research for Candela Lasers, Lumenis, Allergan/AbbVie, InMode, and Endymed. She is also the founder and CEO of Macrene Actives. Dr. Gold disclosed that he is a consultant to and/or an investigator and a speaker for Joylux, InMode, and Alma Lasers.
PHOENIX –
“Even a cursory review of PubMed today yields over 100,000 results” on this topic, Macrene R. Alexiades, MD, PhD, associate clinical professor of dermatology at Yale University, New Haven, Conn., said at the annual conference of the American Society for Laser Medicine and Surgery. “Add to that radiofrequency and various diagnoses, the number of publications has skyrocketed, particularly over the last 10 years.”
What has been missing from this hot research topic all these years, she continued, is that no one has distilled this pile of data into a practical guide for office-based clinicians who use lasers and energy-based devices for genitourinary conditions – until now. Working with experts in gynecology and urogynecology, Dr. Alexiades spearheaded a 2-year-long effort to assemble a document on optimal protocols and best practices for genitourinary application of lasers and energy-based devices. The document, published soon after the ASLMS meeting in Lasers in Medicine and Surgery, includes a table that lists the current Food and Drug Administration approval status of devices in genitourinary applications, as well as individual sections dedicated to fractional lasers, radiofrequency (RF) devices, and high-intensity focused electromagnetic technology. It concludes with a section on the current status of clearances and future pathways.
“The work we did was exhaustive,” said Dr. Alexiades, who is also founder and director of Dermatology & Laser Surgery Center of New York. “We went through all the clinical trial data and compiled the parameters that, as a consensus, we agree are best practices for each technology for which we had rigorous published data.”
The document contains a brief background on the history of the devices used for genitourinary issues and it addresses core topics for each technology, such as conditions treated, contraindications, preoperative physical assessment and preparation, perioperative protocols, and postoperative care.
Contraindications to the genitourinary use of lasers and energy-based devices are numerous and include use of an intrauterine device, active urinary tract or genital infection, vaginal bleeding, current pregnancy, active or recent malignancy, having an electrical implant anywhere in the body, significant concurrent illness, and an anticoagulative or thromboembolic condition or taking anticoagulant medications 1 week prior to the procedure. Another condition to screen for is advanced prolapse, which was considered a contraindication in all clinical trials, she added. “It’s important that you’re able to do the speculum exam and stage the prolapse” so that a patient with this contraindication is not treated.
Dr. Alexiades shared the following highlights from the document’s section related to the use of fractional CO2 lasers:
Preoperative management. Schedule the treatment one week after the patient’s menstrual period. Patients should avoid blood thinners for 7 days and avoid intercourse the night before the procedure. Reschedule in the case of fever, chills, or vaginal bleeding or discharge.
Preoperative physical exam and testing. A normal speculum exam and a recent negative PAP smear are required. For those of child-bearing potential, a pregnancy test is warranted. Obtain written and verbal consent, including discussion of all treatment options, risks, and benefits. No topical or local anesthesia is necessary internally. “Externally, we sometimes apply topical lidocaine gel, but I have found that’s not necessary in most cases,” Dr. Alexiades said. “The treatment is so quick.”
Peri-operative management. In general, device settings are provided by the manufacturer. “For most of the studies that had successful outcomes and no adverse events, researchers adhered to the mild or moderate settings on the technology,” she said. Energy settings were between 15 and 30 watts, delivered at a laser fluence of about 250-300 mJ/cm2 with a spacing of microbeams 1 mm apart. Typically, three treatments are done at 1-month intervals and maintenance treatments are recommended at 6 and 12 months based on duration of the outcomes.
Vulvovaginal postoperative management. A 3-day recovery time is recommended with avoidance of intercourse during this period, because “re-epithelialization is usually complete in 3 days, so we want to give the opportunity for the lining to heal prior to introducing any friction, Dr. Alexiades said.” Rarely, spotting or discharge may occur and there should be no discomfort. “Any severe discomfort or burning may potentially signify infection and should prompt evaluation and possibly vaginal cultures. The patient can shower, but we recommend avoiding seated baths to decrease any introduction of infectious agents.”
Patients should be followed up monthly until three treatments are completed, and a maintenance treatment is considered appropriate between 6 and 12 months. “I do recommend doing a 1-month follow-up following the final treatment, unless it’s a patient who has already had a series of three treatments and is coming in for maintenance,” she said.
In a study from her own practice, Dr. Alexiades evaluated a series of three fractional CO2 laser treatments to the vulva and vagina with a 1-year follow-up in postmenopausal patients. She used the Vaginal Health Index (VHI) to assess changes in vaginal elasticity, fluid volume, vaginal pH, epithelial integrity, and moisture. She and her colleagues discovered that there was improvement in every VHI category after treatment and during the follow-up interval up to 6 months.
“Between 6 and 12 months, we started to see a return a bit toward baseline on all of these parameters,” she said. “The serendipitous discovery that I made during the course of that study was that early intervention improves outcomes. I observed that the younger, most recently postmenopausal cohort seemed to attain normal or near normal VHI quicker than the more extended postmenopausal cohorts.”
In an editorial published in 2020, Dr. Alexiades reviewed the effects of fractional CO2 laser treatment of vulvar skin on vaginal pH and referred to a study she conducted that found that the mean baseline pH pretreatment was 6.32 in the cohort of postmenopausal patients, and was reduced after 3 treatments. “Postmenopausally, the normal acidic pH becomes alkaline,” she said. But she did not expect to see an additional reduction in pH following the treatment out to 6 months. “This indicates that, whatever the wound healing and other restorative effects of these devices are, they seem to continue out to 6 months, at which point it turns around and moves toward baseline [levels].”
Dr. Alexiades highlighted two published meta-analyses of studies related to the genitourinary use of lasers and energy-based devices. One included 59 studies of 3,609 women treated for vaginal rejuvenation using either radiofrequency or fractional ablative laser therapy. The studies reported improvements in symptoms of GSM/VVA and sexual function, high patient satisfaction, with minor adverse events, including treatment-associated vaginal swelling or vaginal discharge.
“Further research needs to be completed to determine which specific pathologies can be treated, if maintenance treatment is necessary, and long-term safety concerns,” the authors concluded.
In another review, researchers analyzed 64 studies related to vaginal laser therapy for GSM. Of these, 47 were before and after studies without a control group, 10 were controlled intervention studies, and 7 were observational cohort and cross-sectional studies.
Vaginal laser treatment “seems to improve scores on the visual analogue scale, Female Sexual Function Index, and the Vaginal Health Index over the short term,” the authors wrote. “Safety outcomes are underreported and short term. Further well-designed clinical trials with sham-laser control groups and evaluating objective variables are needed to provide the best evidence on efficacy.”
“Lasers and energy-based devices are now considered alternative therapeutic modalities for genitourinary conditions,” Dr. Alexiades concluded. “The shortcomings in the literature with respect to lasers and device treatments demonstrate the need for the consensus on best practices and protocols.”
During a separate presentation at the meeting, Michael Gold, MD, highlighted data from Grand View Research, a market research database, which estimated that the global women’s health and wellness market is valued at more than $31 billion globally and is expected to grow at a compound annual growth rate of 4.8% from 2022 to 2030.
“Sales of women’s health energy-based devices continue to grow as new technologies are developed,” said Dr. Gold, a Nashville, Tenn.–based dermatologist and cosmetic surgeon who is also editor-in-chief of the Journal of Cosmetic Dermatology. “Evolving societal norms have made discussions about feminine health issues acceptable. Suffering in silence is no longer necessary or advocated.”
Dr. Alexiades disclosed that she has conducted research for Candela Lasers, Lumenis, Allergan/AbbVie, InMode, and Endymed. She is also the founder and CEO of Macrene Actives. Dr. Gold disclosed that he is a consultant to and/or an investigator and a speaker for Joylux, InMode, and Alma Lasers.
AT ASLMS 2023
Medications provide best risk-to-benefit ratio for weight loss, says expert
Lifestyle changes result in the least weight loss and may be safest, while surgery provides the most weight loss and has the greatest risk. Antiobesity medications, especially the newer ones used in combination with lifestyle changes, can provide significant and sustained weight loss with manageable side effects, said Daniel Bessesen, MD, a professor in the endocrinology, diabetes, and metabolism at University of Colorado at Denver, Aurora.
New and more effective antiobesity medications have given internists more potential options to discuss with their patients, Dr. Bessesen said. He reviewed the pros and cons of the different options.
Medications are indicated for patients with a body mass index greater than 30, including those with a weight-related comorbidity, Dr. Bessesen said. The average weight loss is 5%-15% over 3-6 months but may vary greatly. Insurance often does not cover the medication costs.
Older FDA-approved antiobesity medications
Phentermine is the most widely prescribed antiobesity medication, partly because it is the only option most people can afford out of pocket. Dr. Bessesen presented recent data showing that long-term use of phentermine was associated with greater weight loss and that patients continuously taking phentermine for 24 months lost 7.5% of their weight.
Phentermine suppresses appetite by increasing norepinephrine production. Dr. Bessesen warned that internists should be careful when prescribing it to patients with mental conditions, because it acts as a stimulant. Early studies raised concerns about the risk of cardiovascular disease (CVD) in patients taking phentermine. However, analysis of data from over 13,000 individuals showed no evidence of a relationship between phentermine exposure and CVD events.
“These data provide some reassurance that it could be used in patients with CVD risk,” he noted. Phentermine can also be combined with topiramate extended release, a combination that provides greater efficacy (up to 10% weight loss) with fewer side effects. However, this combination is less effective in patients with diabetes than in those without.
Additional treatment options included orlistat and naltrexone sustained release/bupropion SR. Orlistat is a good treatment alternative for patients with constipation and is the safest option among older anti-obesity medications, whereas naltrexone SR/bupropion SR may be useful in patients with food cravings. However, there is more variability in the individual-level benefit from these agents compared to phentermine and phentermine/topiramate ER, Dr. Bessesen said.
Newer anti‐obesity medications
Liraglutide, an agent used for the management of type 2 diabetes, has recently been approved for weight loss. Liraglutide causes moderate weight loss, and it may reduce the risk of CVD. However, there are tolerability issues, such as nausea and other risks, and Dr. Bessesen advises internists to “start at low doses and increase slowly.”
Semaglutide is the newest and most effective antiobesity drug approved by the Food and Drug Administration, providing sustained weight loss of 8% for up to 48 weeks after starting treatment. Although its efficacy is lower in patients with diabetes, Dr. Bessesen noted that “this is common for antiobesity agents, and clinicians should not refrain from prescribing it in this population.”
Setmelanotide is another new medication approved for chronic weight management in patients with monogenic obesity. This medication can be considered for patients with early-onset severe obesity with abnormal feeding behavior.
Commenting on barriers to access to new antiobesity medications, Dr. Bessesen said that “the high cost of these medications is a substantial problem, but as more companies become involved and products are on the market for a longer period of time, I am hopeful that prices will come down.”
Emerging antiobesity medications
Dr. Bessesen presented recent phase 3 data showing that treatment with tirzepatide provided sustained chronic loss and improved cardiometabolic measures with no diet. Tirzepatide, which targets receptors for glucagonlike peptide–1 and glucose-dependent insulinotropic polypeptide, is used for the management of type 2 diabetes and is expected to be reviewed soon by the FDA for its use in weight management.
A semaglutide/cagrilintide combination may also provide a new treatment option for patients with obesity. In a phase 1b trial, semaglutide/cagrilintide treatment resulted in up to 17% weight loss in patients with obesity who were otherwise healthy; however, phase 2 and 3 data are needed to confirm its efficacy.
A ‘holistic approach’
When deciding whether to prescribe antiobesity medications, Dr. Bessesen noted that medications are better than exercise alone. Factors to consider when deciding whether to prescribe drugs, as well as which ones, include costs, local regulatory guidelines, requirement for long-term use, and patient comorbidities.
He also stated that lifestyle changes, such as adopting healthy nutrition and exercising regularly, are also important and can enhance weight loss when combined with medications.
Richele Corrado, DO, MPH, agreed that lifestyle management in combination with medications may provide greater weight loss than each of these interventions alone.
“If you look at the data, exercise doesn’t help you lose much weight,” said Dr. Corrado, a staff internist and obesity medicine specialist at Walter Reed National Military Medical Center in Bethesda, Md., who spoke at the same session. She added that she has many patients who struggle to lose weight despite having a healthy lifestyle. “It’s important to discuss with these patients about medications and surgery.”
Dr. Bessesen noted that management of mental health and emotional well-being should also be an integral part of obesity management. “Treatment for obesity may be more successful when underlying psychological conditions such as depression, childhood sexual trauma, or anxiety are addressed and treated,” he said.
Dr. Bessesen was involved in the study of the efficacy of semaglutide/cagrilintide. He does not have any financial conflicts with the companies that make other mentioned medications. He has received research grants or contracts from Novo Nordisk, honoraria from Novo Nordisk, and consultantship from Eli Lilly. Dr. Corrado reported no relevant financial conflicts.
Lifestyle changes result in the least weight loss and may be safest, while surgery provides the most weight loss and has the greatest risk. Antiobesity medications, especially the newer ones used in combination with lifestyle changes, can provide significant and sustained weight loss with manageable side effects, said Daniel Bessesen, MD, a professor in the endocrinology, diabetes, and metabolism at University of Colorado at Denver, Aurora.
New and more effective antiobesity medications have given internists more potential options to discuss with their patients, Dr. Bessesen said. He reviewed the pros and cons of the different options.
Medications are indicated for patients with a body mass index greater than 30, including those with a weight-related comorbidity, Dr. Bessesen said. The average weight loss is 5%-15% over 3-6 months but may vary greatly. Insurance often does not cover the medication costs.
Older FDA-approved antiobesity medications
Phentermine is the most widely prescribed antiobesity medication, partly because it is the only option most people can afford out of pocket. Dr. Bessesen presented recent data showing that long-term use of phentermine was associated with greater weight loss and that patients continuously taking phentermine for 24 months lost 7.5% of their weight.
Phentermine suppresses appetite by increasing norepinephrine production. Dr. Bessesen warned that internists should be careful when prescribing it to patients with mental conditions, because it acts as a stimulant. Early studies raised concerns about the risk of cardiovascular disease (CVD) in patients taking phentermine. However, analysis of data from over 13,000 individuals showed no evidence of a relationship between phentermine exposure and CVD events.
“These data provide some reassurance that it could be used in patients with CVD risk,” he noted. Phentermine can also be combined with topiramate extended release, a combination that provides greater efficacy (up to 10% weight loss) with fewer side effects. However, this combination is less effective in patients with diabetes than in those without.
Additional treatment options included orlistat and naltrexone sustained release/bupropion SR. Orlistat is a good treatment alternative for patients with constipation and is the safest option among older anti-obesity medications, whereas naltrexone SR/bupropion SR may be useful in patients with food cravings. However, there is more variability in the individual-level benefit from these agents compared to phentermine and phentermine/topiramate ER, Dr. Bessesen said.
Newer anti‐obesity medications
Liraglutide, an agent used for the management of type 2 diabetes, has recently been approved for weight loss. Liraglutide causes moderate weight loss, and it may reduce the risk of CVD. However, there are tolerability issues, such as nausea and other risks, and Dr. Bessesen advises internists to “start at low doses and increase slowly.”
Semaglutide is the newest and most effective antiobesity drug approved by the Food and Drug Administration, providing sustained weight loss of 8% for up to 48 weeks after starting treatment. Although its efficacy is lower in patients with diabetes, Dr. Bessesen noted that “this is common for antiobesity agents, and clinicians should not refrain from prescribing it in this population.”
Setmelanotide is another new medication approved for chronic weight management in patients with monogenic obesity. This medication can be considered for patients with early-onset severe obesity with abnormal feeding behavior.
Commenting on barriers to access to new antiobesity medications, Dr. Bessesen said that “the high cost of these medications is a substantial problem, but as more companies become involved and products are on the market for a longer period of time, I am hopeful that prices will come down.”
Emerging antiobesity medications
Dr. Bessesen presented recent phase 3 data showing that treatment with tirzepatide provided sustained chronic loss and improved cardiometabolic measures with no diet. Tirzepatide, which targets receptors for glucagonlike peptide–1 and glucose-dependent insulinotropic polypeptide, is used for the management of type 2 diabetes and is expected to be reviewed soon by the FDA for its use in weight management.
A semaglutide/cagrilintide combination may also provide a new treatment option for patients with obesity. In a phase 1b trial, semaglutide/cagrilintide treatment resulted in up to 17% weight loss in patients with obesity who were otherwise healthy; however, phase 2 and 3 data are needed to confirm its efficacy.
A ‘holistic approach’
When deciding whether to prescribe antiobesity medications, Dr. Bessesen noted that medications are better than exercise alone. Factors to consider when deciding whether to prescribe drugs, as well as which ones, include costs, local regulatory guidelines, requirement for long-term use, and patient comorbidities.
He also stated that lifestyle changes, such as adopting healthy nutrition and exercising regularly, are also important and can enhance weight loss when combined with medications.
Richele Corrado, DO, MPH, agreed that lifestyle management in combination with medications may provide greater weight loss than each of these interventions alone.
“If you look at the data, exercise doesn’t help you lose much weight,” said Dr. Corrado, a staff internist and obesity medicine specialist at Walter Reed National Military Medical Center in Bethesda, Md., who spoke at the same session. She added that she has many patients who struggle to lose weight despite having a healthy lifestyle. “It’s important to discuss with these patients about medications and surgery.”
Dr. Bessesen noted that management of mental health and emotional well-being should also be an integral part of obesity management. “Treatment for obesity may be more successful when underlying psychological conditions such as depression, childhood sexual trauma, or anxiety are addressed and treated,” he said.
Dr. Bessesen was involved in the study of the efficacy of semaglutide/cagrilintide. He does not have any financial conflicts with the companies that make other mentioned medications. He has received research grants or contracts from Novo Nordisk, honoraria from Novo Nordisk, and consultantship from Eli Lilly. Dr. Corrado reported no relevant financial conflicts.
Lifestyle changes result in the least weight loss and may be safest, while surgery provides the most weight loss and has the greatest risk. Antiobesity medications, especially the newer ones used in combination with lifestyle changes, can provide significant and sustained weight loss with manageable side effects, said Daniel Bessesen, MD, a professor in the endocrinology, diabetes, and metabolism at University of Colorado at Denver, Aurora.
New and more effective antiobesity medications have given internists more potential options to discuss with their patients, Dr. Bessesen said. He reviewed the pros and cons of the different options.
Medications are indicated for patients with a body mass index greater than 30, including those with a weight-related comorbidity, Dr. Bessesen said. The average weight loss is 5%-15% over 3-6 months but may vary greatly. Insurance often does not cover the medication costs.
Older FDA-approved antiobesity medications
Phentermine is the most widely prescribed antiobesity medication, partly because it is the only option most people can afford out of pocket. Dr. Bessesen presented recent data showing that long-term use of phentermine was associated with greater weight loss and that patients continuously taking phentermine for 24 months lost 7.5% of their weight.
Phentermine suppresses appetite by increasing norepinephrine production. Dr. Bessesen warned that internists should be careful when prescribing it to patients with mental conditions, because it acts as a stimulant. Early studies raised concerns about the risk of cardiovascular disease (CVD) in patients taking phentermine. However, analysis of data from over 13,000 individuals showed no evidence of a relationship between phentermine exposure and CVD events.
“These data provide some reassurance that it could be used in patients with CVD risk,” he noted. Phentermine can also be combined with topiramate extended release, a combination that provides greater efficacy (up to 10% weight loss) with fewer side effects. However, this combination is less effective in patients with diabetes than in those without.
Additional treatment options included orlistat and naltrexone sustained release/bupropion SR. Orlistat is a good treatment alternative for patients with constipation and is the safest option among older anti-obesity medications, whereas naltrexone SR/bupropion SR may be useful in patients with food cravings. However, there is more variability in the individual-level benefit from these agents compared to phentermine and phentermine/topiramate ER, Dr. Bessesen said.
Newer anti‐obesity medications
Liraglutide, an agent used for the management of type 2 diabetes, has recently been approved for weight loss. Liraglutide causes moderate weight loss, and it may reduce the risk of CVD. However, there are tolerability issues, such as nausea and other risks, and Dr. Bessesen advises internists to “start at low doses and increase slowly.”
Semaglutide is the newest and most effective antiobesity drug approved by the Food and Drug Administration, providing sustained weight loss of 8% for up to 48 weeks after starting treatment. Although its efficacy is lower in patients with diabetes, Dr. Bessesen noted that “this is common for antiobesity agents, and clinicians should not refrain from prescribing it in this population.”
Setmelanotide is another new medication approved for chronic weight management in patients with monogenic obesity. This medication can be considered for patients with early-onset severe obesity with abnormal feeding behavior.
Commenting on barriers to access to new antiobesity medications, Dr. Bessesen said that “the high cost of these medications is a substantial problem, but as more companies become involved and products are on the market for a longer period of time, I am hopeful that prices will come down.”
Emerging antiobesity medications
Dr. Bessesen presented recent phase 3 data showing that treatment with tirzepatide provided sustained chronic loss and improved cardiometabolic measures with no diet. Tirzepatide, which targets receptors for glucagonlike peptide–1 and glucose-dependent insulinotropic polypeptide, is used for the management of type 2 diabetes and is expected to be reviewed soon by the FDA for its use in weight management.
A semaglutide/cagrilintide combination may also provide a new treatment option for patients with obesity. In a phase 1b trial, semaglutide/cagrilintide treatment resulted in up to 17% weight loss in patients with obesity who were otherwise healthy; however, phase 2 and 3 data are needed to confirm its efficacy.
A ‘holistic approach’
When deciding whether to prescribe antiobesity medications, Dr. Bessesen noted that medications are better than exercise alone. Factors to consider when deciding whether to prescribe drugs, as well as which ones, include costs, local regulatory guidelines, requirement for long-term use, and patient comorbidities.
He also stated that lifestyle changes, such as adopting healthy nutrition and exercising regularly, are also important and can enhance weight loss when combined with medications.
Richele Corrado, DO, MPH, agreed that lifestyle management in combination with medications may provide greater weight loss than each of these interventions alone.
“If you look at the data, exercise doesn’t help you lose much weight,” said Dr. Corrado, a staff internist and obesity medicine specialist at Walter Reed National Military Medical Center in Bethesda, Md., who spoke at the same session. She added that she has many patients who struggle to lose weight despite having a healthy lifestyle. “It’s important to discuss with these patients about medications and surgery.”
Dr. Bessesen noted that management of mental health and emotional well-being should also be an integral part of obesity management. “Treatment for obesity may be more successful when underlying psychological conditions such as depression, childhood sexual trauma, or anxiety are addressed and treated,” he said.
Dr. Bessesen was involved in the study of the efficacy of semaglutide/cagrilintide. He does not have any financial conflicts with the companies that make other mentioned medications. He has received research grants or contracts from Novo Nordisk, honoraria from Novo Nordisk, and consultantship from Eli Lilly. Dr. Corrado reported no relevant financial conflicts.
AT INTERNAL MEDICINE 2023
Experts debate reducing ASCT for multiple myeloma
NEW YORK –
Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.
A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy.
Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.
“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.
In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.
“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.
He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.
“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.
Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.
“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.
Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.
NEW YORK –
Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.
A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy.
Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.
“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.
In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.
“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.
He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.
“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.
Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.
“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.
Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.
NEW YORK –
Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.
A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy.
Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.
“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.
In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.
“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.
He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.
“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.
Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.
“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.
Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.
AT 2023 GREAT DEBATES AND UPDATES HEMATOLOGIC MALIGNANCIES CONFERENCE