User login
MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Better bone builder: High-intensity exercise vs. Pilates
An 8-month high-intensity resistance and impact training program (HiRIT, Onero) led to greater gains in lumbar spine bone mineral density (BMD) and leg/back strength than a low-intensity Pilates-based program (Buff Bones).
These findings are from the Medication and Exercise for Osteoporosis (MEDEX-OP) trial, which included 115 postmenopausal women with low bone mass. Patients were randomly assigned to attend either the HiRIT or Pilates-based exercise program. The participants attended supervised 45-min sessions twice weekly.
HiRIT was better than the low-intensity Pilates-based exercise program for enhancing bone mass, muscle strength, functional performance, and stature, the researchers reported. The low-intensity program did improve function, but to a lesser extent
Of the 115 participants, most (86) were not taking osteoporosis medicine. For the 29 women who were receiving it, the medication appeared to enhance the effect of exercise.
Melanie Fischbacher, PhD candidate, Griffith University, Gold Coast, Australia, presented these findings in an oral session at the annual meeting of the American Society for Bone and Mineral Research; the study was also published in the Journal of Bone and Mineral Research.
The study’s senior author, Belinda R. Beck, PhD, director of the Bone Clinic in Brisbane, Australia, developed the Onero HiRIT program and has licensed it to others in Australia.
“It is a very effective program and we have shown it can be undertaken safely, but it must be supervised because of the heavy weights and high-risk clientele,” Beck stressed to this news organization.
“This is not a program you should just hand to a patient and tell them to do in a gym,” she said.
“Both forms of exercise in our study were beneficial for functional outcomes but Onero improved back extensor strength, mobility and stature considerably more than Buff Bones,” Ms. Fischbacher said in an interview.
Nevertheless, “the contribution of functional capacity to risk of falling and fracture cannot be overstated, and bone medications do not address function,” she noted.
“More trials combining bone medication and bone-targeted exercise are needed,” the researchers concluded.
Compliance stands out, study supports high-intensity exercise
Kristen M. Beavers, PhD, MPH, RD, who was not involved with this research, told this news organization that participant compliance in the study really stands out.
“Compliance to an 8-month, 2 day/week high-intensity resistance training program among older women with low bone mass was quite good in this study [>80%], with very few adverse events reported,” said Dr. Beavers, of the department of health and exercise science, Wake Forest University, Winston Salem, N.C.
“A lot of individuals wouldn’t even consider recommending this type/intensity of exercise to this population, because they are worried it is too risky and/or the uptake will be low,” she said.
Although the benefit in BMD and strength wasn’t seen universally across all bone/muscle outcomes assessed, the findings do reinforce the idea that high-intensity exercise is more efficacious for bone health than low-intensity exercise, she noted.
“The possible additive effect of high-intensity exercise when combined with medication is worth confirming in larger, adequately designed/powered studies,” according to Dr. Beavers.
“The general consensus in the field is that higher-intensity exercise is more osteogenic than low-intensity exercise, but improving muscle mass, quality, and function (including balance) are also important to reduce the risk of falls, which is a major contributor to incident fracture,” she noted.
Exercise, even low-intensity exercise, reduces the risk for falls, as shown in a recent meta-analysis, she added. This is something antiresorptive medications don’t do.
Building on the LIFTMOR and LIFTMOR-M Trials
Previously, the Australian group showed that HiRIT is efficacious and safe for bone formation in individuals with low to very low bone mass – in postmenopausal women in the LIFTMOR study (J Bone Miner Res. 2017 Oct 4 .doi: 10.1002/jbmr.3284), and in men in the LIFTMOR-M study.
The current study compared two exercise programs. The researchers randomly assigned 86 women who were not taking antiresorptive medication to the high-intensity (42) or low-intensity (44) exercise program. They also assigned 29 women who were receiving antiresorptive medication to the high-intensity (15) or low-intensity (14) exercise program.
In the high-intensity exercise plus medication subgroup, the women were taking denosumab (12), risedronate (2) or alendronate (1). In the low-intensity exercise plus medication subgroup, the women were taking denosumab (9), risedronate (1), alendronate (3), or zoledronic acid (1).
The mean age of the women was 64-68 years. The mean lumbar spine T score was –1.5 to –2.3, and the mean femoral neck T score was –1.7 to –2.0 (determined by dual-energy x-ray absorptiometry) .
The HiRIT training program consisted of three free-weight resistance training exercises (deadlift, back squat, overhead press), one high-impact exercise (jump drop), and two balance exercises. The exercises varied each session.
The low-intensity training consisted of bone-specific Pilates-based exercises performed on the mat; standing weight-bearing exercise with 1-kg dumbbells; and impact exercises, such as heel drops and stomping.
At 8 months, compared with women in the low-intensity exercise program, those in the HiRIT program demonstrated greater improvement in lumbar spine BMD (1.9% vs. 0.1%) and stature (0.2 cm vs. 0.0 cm), muscle strength, and functional performance.
Functional performance improved with both exercise programs, but the HiRIT program led to greater leg and back muscle strength and better results in the five times sit-to-stand test (P < .05).
HiRIT plus bone medication improved BMD at the femoral neck and total hip, whereas HiRIT alone did not. Low-intensity exercise plus bone medication improved BMD at the lumbar spine and total hip, whereas low-intensity exercise alone did not.
The retention rate was 90%. The rate of exercise compliance was 83% in the high-intensity group and 82% in the low-intensity group.
Thirty falls were reported by 24 participants (21%). One fracture occurred in each exercise group. Three adverse events occurred in the low-intensity group, and four occurred in the high-intensity group.
Dr. Beck owns the Bone Clinic and sells licenses to the Onero program. The other researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An 8-month high-intensity resistance and impact training program (HiRIT, Onero) led to greater gains in lumbar spine bone mineral density (BMD) and leg/back strength than a low-intensity Pilates-based program (Buff Bones).
These findings are from the Medication and Exercise for Osteoporosis (MEDEX-OP) trial, which included 115 postmenopausal women with low bone mass. Patients were randomly assigned to attend either the HiRIT or Pilates-based exercise program. The participants attended supervised 45-min sessions twice weekly.
HiRIT was better than the low-intensity Pilates-based exercise program for enhancing bone mass, muscle strength, functional performance, and stature, the researchers reported. The low-intensity program did improve function, but to a lesser extent
Of the 115 participants, most (86) were not taking osteoporosis medicine. For the 29 women who were receiving it, the medication appeared to enhance the effect of exercise.
Melanie Fischbacher, PhD candidate, Griffith University, Gold Coast, Australia, presented these findings in an oral session at the annual meeting of the American Society for Bone and Mineral Research; the study was also published in the Journal of Bone and Mineral Research.
The study’s senior author, Belinda R. Beck, PhD, director of the Bone Clinic in Brisbane, Australia, developed the Onero HiRIT program and has licensed it to others in Australia.
“It is a very effective program and we have shown it can be undertaken safely, but it must be supervised because of the heavy weights and high-risk clientele,” Beck stressed to this news organization.
“This is not a program you should just hand to a patient and tell them to do in a gym,” she said.
“Both forms of exercise in our study were beneficial for functional outcomes but Onero improved back extensor strength, mobility and stature considerably more than Buff Bones,” Ms. Fischbacher said in an interview.
Nevertheless, “the contribution of functional capacity to risk of falling and fracture cannot be overstated, and bone medications do not address function,” she noted.
“More trials combining bone medication and bone-targeted exercise are needed,” the researchers concluded.
Compliance stands out, study supports high-intensity exercise
Kristen M. Beavers, PhD, MPH, RD, who was not involved with this research, told this news organization that participant compliance in the study really stands out.
“Compliance to an 8-month, 2 day/week high-intensity resistance training program among older women with low bone mass was quite good in this study [>80%], with very few adverse events reported,” said Dr. Beavers, of the department of health and exercise science, Wake Forest University, Winston Salem, N.C.
“A lot of individuals wouldn’t even consider recommending this type/intensity of exercise to this population, because they are worried it is too risky and/or the uptake will be low,” she said.
Although the benefit in BMD and strength wasn’t seen universally across all bone/muscle outcomes assessed, the findings do reinforce the idea that high-intensity exercise is more efficacious for bone health than low-intensity exercise, she noted.
“The possible additive effect of high-intensity exercise when combined with medication is worth confirming in larger, adequately designed/powered studies,” according to Dr. Beavers.
“The general consensus in the field is that higher-intensity exercise is more osteogenic than low-intensity exercise, but improving muscle mass, quality, and function (including balance) are also important to reduce the risk of falls, which is a major contributor to incident fracture,” she noted.
Exercise, even low-intensity exercise, reduces the risk for falls, as shown in a recent meta-analysis, she added. This is something antiresorptive medications don’t do.
Building on the LIFTMOR and LIFTMOR-M Trials
Previously, the Australian group showed that HiRIT is efficacious and safe for bone formation in individuals with low to very low bone mass – in postmenopausal women in the LIFTMOR study (J Bone Miner Res. 2017 Oct 4 .doi: 10.1002/jbmr.3284), and in men in the LIFTMOR-M study.
The current study compared two exercise programs. The researchers randomly assigned 86 women who were not taking antiresorptive medication to the high-intensity (42) or low-intensity (44) exercise program. They also assigned 29 women who were receiving antiresorptive medication to the high-intensity (15) or low-intensity (14) exercise program.
In the high-intensity exercise plus medication subgroup, the women were taking denosumab (12), risedronate (2) or alendronate (1). In the low-intensity exercise plus medication subgroup, the women were taking denosumab (9), risedronate (1), alendronate (3), or zoledronic acid (1).
The mean age of the women was 64-68 years. The mean lumbar spine T score was –1.5 to –2.3, and the mean femoral neck T score was –1.7 to –2.0 (determined by dual-energy x-ray absorptiometry) .
The HiRIT training program consisted of three free-weight resistance training exercises (deadlift, back squat, overhead press), one high-impact exercise (jump drop), and two balance exercises. The exercises varied each session.
The low-intensity training consisted of bone-specific Pilates-based exercises performed on the mat; standing weight-bearing exercise with 1-kg dumbbells; and impact exercises, such as heel drops and stomping.
At 8 months, compared with women in the low-intensity exercise program, those in the HiRIT program demonstrated greater improvement in lumbar spine BMD (1.9% vs. 0.1%) and stature (0.2 cm vs. 0.0 cm), muscle strength, and functional performance.
Functional performance improved with both exercise programs, but the HiRIT program led to greater leg and back muscle strength and better results in the five times sit-to-stand test (P < .05).
HiRIT plus bone medication improved BMD at the femoral neck and total hip, whereas HiRIT alone did not. Low-intensity exercise plus bone medication improved BMD at the lumbar spine and total hip, whereas low-intensity exercise alone did not.
The retention rate was 90%. The rate of exercise compliance was 83% in the high-intensity group and 82% in the low-intensity group.
Thirty falls were reported by 24 participants (21%). One fracture occurred in each exercise group. Three adverse events occurred in the low-intensity group, and four occurred in the high-intensity group.
Dr. Beck owns the Bone Clinic and sells licenses to the Onero program. The other researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An 8-month high-intensity resistance and impact training program (HiRIT, Onero) led to greater gains in lumbar spine bone mineral density (BMD) and leg/back strength than a low-intensity Pilates-based program (Buff Bones).
These findings are from the Medication and Exercise for Osteoporosis (MEDEX-OP) trial, which included 115 postmenopausal women with low bone mass. Patients were randomly assigned to attend either the HiRIT or Pilates-based exercise program. The participants attended supervised 45-min sessions twice weekly.
HiRIT was better than the low-intensity Pilates-based exercise program for enhancing bone mass, muscle strength, functional performance, and stature, the researchers reported. The low-intensity program did improve function, but to a lesser extent
Of the 115 participants, most (86) were not taking osteoporosis medicine. For the 29 women who were receiving it, the medication appeared to enhance the effect of exercise.
Melanie Fischbacher, PhD candidate, Griffith University, Gold Coast, Australia, presented these findings in an oral session at the annual meeting of the American Society for Bone and Mineral Research; the study was also published in the Journal of Bone and Mineral Research.
The study’s senior author, Belinda R. Beck, PhD, director of the Bone Clinic in Brisbane, Australia, developed the Onero HiRIT program and has licensed it to others in Australia.
“It is a very effective program and we have shown it can be undertaken safely, but it must be supervised because of the heavy weights and high-risk clientele,” Beck stressed to this news organization.
“This is not a program you should just hand to a patient and tell them to do in a gym,” she said.
“Both forms of exercise in our study were beneficial for functional outcomes but Onero improved back extensor strength, mobility and stature considerably more than Buff Bones,” Ms. Fischbacher said in an interview.
Nevertheless, “the contribution of functional capacity to risk of falling and fracture cannot be overstated, and bone medications do not address function,” she noted.
“More trials combining bone medication and bone-targeted exercise are needed,” the researchers concluded.
Compliance stands out, study supports high-intensity exercise
Kristen M. Beavers, PhD, MPH, RD, who was not involved with this research, told this news organization that participant compliance in the study really stands out.
“Compliance to an 8-month, 2 day/week high-intensity resistance training program among older women with low bone mass was quite good in this study [>80%], with very few adverse events reported,” said Dr. Beavers, of the department of health and exercise science, Wake Forest University, Winston Salem, N.C.
“A lot of individuals wouldn’t even consider recommending this type/intensity of exercise to this population, because they are worried it is too risky and/or the uptake will be low,” she said.
Although the benefit in BMD and strength wasn’t seen universally across all bone/muscle outcomes assessed, the findings do reinforce the idea that high-intensity exercise is more efficacious for bone health than low-intensity exercise, she noted.
“The possible additive effect of high-intensity exercise when combined with medication is worth confirming in larger, adequately designed/powered studies,” according to Dr. Beavers.
“The general consensus in the field is that higher-intensity exercise is more osteogenic than low-intensity exercise, but improving muscle mass, quality, and function (including balance) are also important to reduce the risk of falls, which is a major contributor to incident fracture,” she noted.
Exercise, even low-intensity exercise, reduces the risk for falls, as shown in a recent meta-analysis, she added. This is something antiresorptive medications don’t do.
Building on the LIFTMOR and LIFTMOR-M Trials
Previously, the Australian group showed that HiRIT is efficacious and safe for bone formation in individuals with low to very low bone mass – in postmenopausal women in the LIFTMOR study (J Bone Miner Res. 2017 Oct 4 .doi: 10.1002/jbmr.3284), and in men in the LIFTMOR-M study.
The current study compared two exercise programs. The researchers randomly assigned 86 women who were not taking antiresorptive medication to the high-intensity (42) or low-intensity (44) exercise program. They also assigned 29 women who were receiving antiresorptive medication to the high-intensity (15) or low-intensity (14) exercise program.
In the high-intensity exercise plus medication subgroup, the women were taking denosumab (12), risedronate (2) or alendronate (1). In the low-intensity exercise plus medication subgroup, the women were taking denosumab (9), risedronate (1), alendronate (3), or zoledronic acid (1).
The mean age of the women was 64-68 years. The mean lumbar spine T score was –1.5 to –2.3, and the mean femoral neck T score was –1.7 to –2.0 (determined by dual-energy x-ray absorptiometry) .
The HiRIT training program consisted of three free-weight resistance training exercises (deadlift, back squat, overhead press), one high-impact exercise (jump drop), and two balance exercises. The exercises varied each session.
The low-intensity training consisted of bone-specific Pilates-based exercises performed on the mat; standing weight-bearing exercise with 1-kg dumbbells; and impact exercises, such as heel drops and stomping.
At 8 months, compared with women in the low-intensity exercise program, those in the HiRIT program demonstrated greater improvement in lumbar spine BMD (1.9% vs. 0.1%) and stature (0.2 cm vs. 0.0 cm), muscle strength, and functional performance.
Functional performance improved with both exercise programs, but the HiRIT program led to greater leg and back muscle strength and better results in the five times sit-to-stand test (P < .05).
HiRIT plus bone medication improved BMD at the femoral neck and total hip, whereas HiRIT alone did not. Low-intensity exercise plus bone medication improved BMD at the lumbar spine and total hip, whereas low-intensity exercise alone did not.
The retention rate was 90%. The rate of exercise compliance was 83% in the high-intensity group and 82% in the low-intensity group.
Thirty falls were reported by 24 participants (21%). One fracture occurred in each exercise group. Three adverse events occurred in the low-intensity group, and four occurred in the high-intensity group.
Dr. Beck owns the Bone Clinic and sells licenses to the Onero program. The other researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In MS, baseline cortical lesions predict cognitive decline
, according to findings from a new analysis. The findings had good accuracy, and could help clinicians monitor and treat cognitive impairment as it develops, according to Stefano Ziccardi, PhD, who is a postdoctoral researcher at the University of Verona in Italy.
“The number of cortical lesions at MS diagnosis accurately discriminates between the presence or the absence of cognitive impairment after diagnosis of MS, and this should be considered a predictive marker of long-term cognitive impairment in these patients. Early cortical lesion evaluation should be conducted in each MS patient to anticipate the manifestation of cognitive problems to improve the monitoring of cognitive abilities, improve the diagnosis of cognitive impairment, enable prompt intervention as necessary,” said Dr. Ziccardi at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Cortical lesions are highly prevalent in MS, perhaps more so than white matter lesions, said Dr. Ziccardi. They are associated with clinical disability and lead to disease progression. “However, prognostic data about the role of early cortical lesions with reference to long-term cognitive impairment are still missing,” said Dr. Ziccardi.
That’s important because cognitive impairment is very common in MS, affecting between one-third and two-thirds of patients. It may appear early in the disease course and worsen over time, and it predicts worse clinical and neurological progression. And it presents a clinical challenge. “Clinicians struggle to predict the evolution of cognitive abilities over time,” said Dr. Ziccardi.
The findings drew praise from Iris-Katharina Penner, PhD, who comoderated the session. “I think the important point … is that the predictive value of cortical lesions is very high, because it indicates finally that we probably have a patient at risk for developing cognitive impairment in the future,” said Dr. Penner, who is a neuropsychologist and cognitive neuroscientist at Heinrich Heine University in Düsseldorf, Germany.
Clinicians often don’t pay enough attention to cognition and the complexities of MS, said Mark Gudesblatt, MD, who was asked to comment. “It’s just adding layers of complexity. We’re peeling back the onion and you realize it’s a really complicated disease. It’s not just white matter plaques, gray matter plaques, disconnection syndrome, wires cut, atrophy, ongoing inflammation, immune deficiency. All these diseases are fascinating. And we think we’re experts. But the fact is, we have much to learn,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, New York.
The researchers analyzed data from 170 patients with MS who had a disease duration of approximately 20 years. Among the study cohort 62 patients were female, and the mean duration of disease was 19.2 years. Each patient had had a 1.5 Tesla magnetic resonance imaging scan to look for cortical lesions within 3 years of diagnosis. They had also undergone periodic MRIs as well as neuropsychological exams, and underwent a neuropsychological assessment at the end of the study, which included the Brief Repeatable Battery of Neuropsychological Tests (BRB-NT) and the Stroop Test.
A total of 41% of subjects had no cortical lesions according to their first MRI; 19% had 1-2 lesions, and 40% had 3 or more. At follow-up, 50% were cognitively normal (failed no tests), 25% had mild cognitive impairment (failed one or more tests), and 25% had severe cognitive impairment (failed three or more tests).
In the overall cohort, the median number of cortical lesions at baseline was 1 (interquartile range, 5.0). Among the 50% with normal cognitive function, the median was 0 (IQR, 2.5), while for the remaining 50% with cognitive impairment, the median was 3 (IQR, 7.0).
Those with 3 or more lesions had increased odds of cognitive impairment at follow-up (odds ratio, 3.70; P < .001), with an accuracy of 65% (95% confidence interval, 58%-72%), specificity of 75% (95% CI, 65%-84%), and a sensitivity of 55% (95% CI, 44%-66%). Three or more lesions discriminated between cognitive impairment and no impairment with an area under the curve of 0.67.
Individuals with no cognitive impairment had a median 0 lesions (IQR, 2.5), those with mild cognitive impairment had a median of 2.0 (IQR, 6.0), and those with severe cognitive impairment had 4.0 (IQR, 7.25).
In a multinomial regression model, 3 or more baseline cortical lesions were associated with a greater than threefold risk of severe cognitive impairment (OR, 3.33; P = .01).
Of subjects with 0 baseline lesions, 62% were cognitively normal at follow-up. In the 1-2 lesion group, 64% were normal. In the 3 or more group, 31% were cognitively normal (P < .001). In the 0 lesion group, 26% had mild cognitive impairment and 12% had severe cognitive impairment. In the 3 or more group, 28% had mild cognitive impairment, and 41% had severe cognitive impairment.
During the Q&A session following the talk, Dr. Ziccardi was asked if the group compared cortical lesions to other MRI correlates of cognitive impairment, such as gray matter volume or white matter integrity. He responded that the group is looking into those comparisons, and recently found that neither the number nor the volume of white matter lesions improved the accuracy of the predictive models based on the number of cortical lesions. The group is also looking into the applicability of gray matter volume.
, according to findings from a new analysis. The findings had good accuracy, and could help clinicians monitor and treat cognitive impairment as it develops, according to Stefano Ziccardi, PhD, who is a postdoctoral researcher at the University of Verona in Italy.
“The number of cortical lesions at MS diagnosis accurately discriminates between the presence or the absence of cognitive impairment after diagnosis of MS, and this should be considered a predictive marker of long-term cognitive impairment in these patients. Early cortical lesion evaluation should be conducted in each MS patient to anticipate the manifestation of cognitive problems to improve the monitoring of cognitive abilities, improve the diagnosis of cognitive impairment, enable prompt intervention as necessary,” said Dr. Ziccardi at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Cortical lesions are highly prevalent in MS, perhaps more so than white matter lesions, said Dr. Ziccardi. They are associated with clinical disability and lead to disease progression. “However, prognostic data about the role of early cortical lesions with reference to long-term cognitive impairment are still missing,” said Dr. Ziccardi.
That’s important because cognitive impairment is very common in MS, affecting between one-third and two-thirds of patients. It may appear early in the disease course and worsen over time, and it predicts worse clinical and neurological progression. And it presents a clinical challenge. “Clinicians struggle to predict the evolution of cognitive abilities over time,” said Dr. Ziccardi.
The findings drew praise from Iris-Katharina Penner, PhD, who comoderated the session. “I think the important point … is that the predictive value of cortical lesions is very high, because it indicates finally that we probably have a patient at risk for developing cognitive impairment in the future,” said Dr. Penner, who is a neuropsychologist and cognitive neuroscientist at Heinrich Heine University in Düsseldorf, Germany.
Clinicians often don’t pay enough attention to cognition and the complexities of MS, said Mark Gudesblatt, MD, who was asked to comment. “It’s just adding layers of complexity. We’re peeling back the onion and you realize it’s a really complicated disease. It’s not just white matter plaques, gray matter plaques, disconnection syndrome, wires cut, atrophy, ongoing inflammation, immune deficiency. All these diseases are fascinating. And we think we’re experts. But the fact is, we have much to learn,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, New York.
The researchers analyzed data from 170 patients with MS who had a disease duration of approximately 20 years. Among the study cohort 62 patients were female, and the mean duration of disease was 19.2 years. Each patient had had a 1.5 Tesla magnetic resonance imaging scan to look for cortical lesions within 3 years of diagnosis. They had also undergone periodic MRIs as well as neuropsychological exams, and underwent a neuropsychological assessment at the end of the study, which included the Brief Repeatable Battery of Neuropsychological Tests (BRB-NT) and the Stroop Test.
A total of 41% of subjects had no cortical lesions according to their first MRI; 19% had 1-2 lesions, and 40% had 3 or more. At follow-up, 50% were cognitively normal (failed no tests), 25% had mild cognitive impairment (failed one or more tests), and 25% had severe cognitive impairment (failed three or more tests).
In the overall cohort, the median number of cortical lesions at baseline was 1 (interquartile range, 5.0). Among the 50% with normal cognitive function, the median was 0 (IQR, 2.5), while for the remaining 50% with cognitive impairment, the median was 3 (IQR, 7.0).
Those with 3 or more lesions had increased odds of cognitive impairment at follow-up (odds ratio, 3.70; P < .001), with an accuracy of 65% (95% confidence interval, 58%-72%), specificity of 75% (95% CI, 65%-84%), and a sensitivity of 55% (95% CI, 44%-66%). Three or more lesions discriminated between cognitive impairment and no impairment with an area under the curve of 0.67.
Individuals with no cognitive impairment had a median 0 lesions (IQR, 2.5), those with mild cognitive impairment had a median of 2.0 (IQR, 6.0), and those with severe cognitive impairment had 4.0 (IQR, 7.25).
In a multinomial regression model, 3 or more baseline cortical lesions were associated with a greater than threefold risk of severe cognitive impairment (OR, 3.33; P = .01).
Of subjects with 0 baseline lesions, 62% were cognitively normal at follow-up. In the 1-2 lesion group, 64% were normal. In the 3 or more group, 31% were cognitively normal (P < .001). In the 0 lesion group, 26% had mild cognitive impairment and 12% had severe cognitive impairment. In the 3 or more group, 28% had mild cognitive impairment, and 41% had severe cognitive impairment.
During the Q&A session following the talk, Dr. Ziccardi was asked if the group compared cortical lesions to other MRI correlates of cognitive impairment, such as gray matter volume or white matter integrity. He responded that the group is looking into those comparisons, and recently found that neither the number nor the volume of white matter lesions improved the accuracy of the predictive models based on the number of cortical lesions. The group is also looking into the applicability of gray matter volume.
, according to findings from a new analysis. The findings had good accuracy, and could help clinicians monitor and treat cognitive impairment as it develops, according to Stefano Ziccardi, PhD, who is a postdoctoral researcher at the University of Verona in Italy.
“The number of cortical lesions at MS diagnosis accurately discriminates between the presence or the absence of cognitive impairment after diagnosis of MS, and this should be considered a predictive marker of long-term cognitive impairment in these patients. Early cortical lesion evaluation should be conducted in each MS patient to anticipate the manifestation of cognitive problems to improve the monitoring of cognitive abilities, improve the diagnosis of cognitive impairment, enable prompt intervention as necessary,” said Dr. Ziccardi at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Cortical lesions are highly prevalent in MS, perhaps more so than white matter lesions, said Dr. Ziccardi. They are associated with clinical disability and lead to disease progression. “However, prognostic data about the role of early cortical lesions with reference to long-term cognitive impairment are still missing,” said Dr. Ziccardi.
That’s important because cognitive impairment is very common in MS, affecting between one-third and two-thirds of patients. It may appear early in the disease course and worsen over time, and it predicts worse clinical and neurological progression. And it presents a clinical challenge. “Clinicians struggle to predict the evolution of cognitive abilities over time,” said Dr. Ziccardi.
The findings drew praise from Iris-Katharina Penner, PhD, who comoderated the session. “I think the important point … is that the predictive value of cortical lesions is very high, because it indicates finally that we probably have a patient at risk for developing cognitive impairment in the future,” said Dr. Penner, who is a neuropsychologist and cognitive neuroscientist at Heinrich Heine University in Düsseldorf, Germany.
Clinicians often don’t pay enough attention to cognition and the complexities of MS, said Mark Gudesblatt, MD, who was asked to comment. “It’s just adding layers of complexity. We’re peeling back the onion and you realize it’s a really complicated disease. It’s not just white matter plaques, gray matter plaques, disconnection syndrome, wires cut, atrophy, ongoing inflammation, immune deficiency. All these diseases are fascinating. And we think we’re experts. But the fact is, we have much to learn,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, New York.
The researchers analyzed data from 170 patients with MS who had a disease duration of approximately 20 years. Among the study cohort 62 patients were female, and the mean duration of disease was 19.2 years. Each patient had had a 1.5 Tesla magnetic resonance imaging scan to look for cortical lesions within 3 years of diagnosis. They had also undergone periodic MRIs as well as neuropsychological exams, and underwent a neuropsychological assessment at the end of the study, which included the Brief Repeatable Battery of Neuropsychological Tests (BRB-NT) and the Stroop Test.
A total of 41% of subjects had no cortical lesions according to their first MRI; 19% had 1-2 lesions, and 40% had 3 or more. At follow-up, 50% were cognitively normal (failed no tests), 25% had mild cognitive impairment (failed one or more tests), and 25% had severe cognitive impairment (failed three or more tests).
In the overall cohort, the median number of cortical lesions at baseline was 1 (interquartile range, 5.0). Among the 50% with normal cognitive function, the median was 0 (IQR, 2.5), while for the remaining 50% with cognitive impairment, the median was 3 (IQR, 7.0).
Those with 3 or more lesions had increased odds of cognitive impairment at follow-up (odds ratio, 3.70; P < .001), with an accuracy of 65% (95% confidence interval, 58%-72%), specificity of 75% (95% CI, 65%-84%), and a sensitivity of 55% (95% CI, 44%-66%). Three or more lesions discriminated between cognitive impairment and no impairment with an area under the curve of 0.67.
Individuals with no cognitive impairment had a median 0 lesions (IQR, 2.5), those with mild cognitive impairment had a median of 2.0 (IQR, 6.0), and those with severe cognitive impairment had 4.0 (IQR, 7.25).
In a multinomial regression model, 3 or more baseline cortical lesions were associated with a greater than threefold risk of severe cognitive impairment (OR, 3.33; P = .01).
Of subjects with 0 baseline lesions, 62% were cognitively normal at follow-up. In the 1-2 lesion group, 64% were normal. In the 3 or more group, 31% were cognitively normal (P < .001). In the 0 lesion group, 26% had mild cognitive impairment and 12% had severe cognitive impairment. In the 3 or more group, 28% had mild cognitive impairment, and 41% had severe cognitive impairment.
During the Q&A session following the talk, Dr. Ziccardi was asked if the group compared cortical lesions to other MRI correlates of cognitive impairment, such as gray matter volume or white matter integrity. He responded that the group is looking into those comparisons, and recently found that neither the number nor the volume of white matter lesions improved the accuracy of the predictive models based on the number of cortical lesions. The group is also looking into the applicability of gray matter volume.
FROM ECTRIMS 2021
Cortical lesions predict risk for secondary progressive MS
(MS), according to new research. Cortical lesions also may be an early marker of future disability accumulation.
In the study, patients who had developed secondary progressive MS after 20 years of follow-up had approximately 7 cortical lesions at baseline. This number was significantly higher than the baseline number of cortical lesions in patients with clinically isolated syndrome (CIS), relapsing-remitting MS, or primary progressive MS at 20 years.
“Our study represented a clear indication that the assessment, presence, and high number of cortical lesions at diagnosis is one of the tools at the disposal of the neurologist for the early identification of patients with more serious disease course,” said Gian Marco Schiavi, MD, a neurology resident at the University of Verona, Italy, during the presentation of his research.
The study was presented October 14 at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Accumulation of disability
Previous research has indicated that cortical lesions play a role in the accumulation of disability in MS and the conversion to secondary progressive MS. Other observations suggest that the number of cortical lesions after 30 years of follow-up explains more than 40% of the difference in disability between patients with secondary progressive MS.
The current investigators sought to understand whether cortical lesions at diagnosis could predict a patient’s risk for development of secondary progressive MS and risk for disability accumulation. They included 220 patients with MS and approximately 20 years of follow-up in their study.
At the time of diagnosis, all participants underwent 1.5-T MRI with double inversion recovery. Participants also presented for periodic MRI and clinical evaluations.
The researchers used analysis of variance to compare the baseline number of cortical lesions between patients with CIS, relapsing-remitting MS, secondary progressive MS, and primary progressive MS at 20 years. They also performed a multivariable regression analysis to predict patients’ final scores on the Expanded Disability Status Scale (EDSS). Variables included participants’ demographic, clinical, and radiological characteristics.
Lesions and disease progression
At baseline (the time of diagnosis), 162 patients had relapsing-remitting MS, 45 had CIS, and 12 had primary progressive MS. In all, 106 patients had no cortical lesions, 47 had 3 or fewer cortical lesions, and 67 had more than 3 cortical lesions.
At 20 years, 12 patients still had CIS, 152 had relapsing-remitting MS, and 44 had developed secondary progressive MS.
The mean number of cortical lesions at diagnosis was 6.6 in patients with secondary progressive MS at 20 years, which was significantly higher than the mean 1.3 cortical lesions in the other patients (P < .001).
In addition, post-hoc analysis showed that the median number of cortical lesions was significantly higher in patients with secondary progressive MS (6), compared with those with CIS (0; P < .001), relapsing-remitting MS (0; P < .001), and primary progressive MS (4.5; P = .013). Patients with primary progressive MS had a higher number of cortical lesions than patients with CIS and those with relapsing-remitting MS (P = .001).
The investigators also examined disability at 20 years. At that timepoint, mean EDSS score was 1.5 in patients with no cortical lesions, 3.0 in patients with 1 to 3 cortical lesions at baseline, and 6.0 in patients with more than 3 cortical lesions.
In a regression analysis, the number of cortical lesions and EDSS at diagnosis were the best predictors of long-term disability (P < .001). These factors explained about 57% of the variance in EDSS score after 20 years.
‘Important study’
“This important study supports that the presence of cortical lesions at the time of diagnosis is associated with long-term disability and transition to a secondary progressive disease course,” said Elias S. Sotirchos, MD, assistant professor of neurology at Johns Hopkins University, Baltimore. The study size and long duration of follow-up are important strengths of the findings, he added.
Still, further research is needed to validate cortical lesions as a biomarker in clinical practice. Aside from technical validation issues relating to the identification of cortical lesions, whether cortical lesion burden can be used to guide therapeutic decision-making in MS is not clear, said Dr. Sotirchos.
“Notably, these patients were diagnosed and enrolled in this study 20 years ago, prior to the availability of newer disease-modifying therapies [DMTs] that are more effective at preventing inflammatory disease activity in MS,” he said, referring to the participants in the current study.
While recent observational studies have suggested that early initiation of higher-efficacy disease-modifying therapies (DMTs) may reduce long-term disability and risk for transition to secondary progressive MS, the optimal approach to treatment in patients with a new diagnosis remains unclear, said Dr. Sotirchos.
Furthermore, it is unknown whether use of higher-efficacy DMTs may affect the risk of future disability in patients with high cortical lesion burden at baseline, said Dr. Sotirchos. “Or is it too late, especially considering the modest effects of DMTs in progressive patients and that cortical lesion burden was higher in patients that are progressive?”
One additional question to be addressed is how baseline cortical lesion burden adds to other factors that neurologists use in clinical practice to stratify patients’ risk of future disability, such as spinal cord involvement, motor or sphincter symptoms at onset, poor recovery from attacks, and white matter lesion burden, said Dr. Sotirchos.
The source of funding for this study was not reported. Dr. Schiavi and Dr. Sotirchos have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(MS), according to new research. Cortical lesions also may be an early marker of future disability accumulation.
In the study, patients who had developed secondary progressive MS after 20 years of follow-up had approximately 7 cortical lesions at baseline. This number was significantly higher than the baseline number of cortical lesions in patients with clinically isolated syndrome (CIS), relapsing-remitting MS, or primary progressive MS at 20 years.
“Our study represented a clear indication that the assessment, presence, and high number of cortical lesions at diagnosis is one of the tools at the disposal of the neurologist for the early identification of patients with more serious disease course,” said Gian Marco Schiavi, MD, a neurology resident at the University of Verona, Italy, during the presentation of his research.
The study was presented October 14 at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Accumulation of disability
Previous research has indicated that cortical lesions play a role in the accumulation of disability in MS and the conversion to secondary progressive MS. Other observations suggest that the number of cortical lesions after 30 years of follow-up explains more than 40% of the difference in disability between patients with secondary progressive MS.
The current investigators sought to understand whether cortical lesions at diagnosis could predict a patient’s risk for development of secondary progressive MS and risk for disability accumulation. They included 220 patients with MS and approximately 20 years of follow-up in their study.
At the time of diagnosis, all participants underwent 1.5-T MRI with double inversion recovery. Participants also presented for periodic MRI and clinical evaluations.
The researchers used analysis of variance to compare the baseline number of cortical lesions between patients with CIS, relapsing-remitting MS, secondary progressive MS, and primary progressive MS at 20 years. They also performed a multivariable regression analysis to predict patients’ final scores on the Expanded Disability Status Scale (EDSS). Variables included participants’ demographic, clinical, and radiological characteristics.
Lesions and disease progression
At baseline (the time of diagnosis), 162 patients had relapsing-remitting MS, 45 had CIS, and 12 had primary progressive MS. In all, 106 patients had no cortical lesions, 47 had 3 or fewer cortical lesions, and 67 had more than 3 cortical lesions.
At 20 years, 12 patients still had CIS, 152 had relapsing-remitting MS, and 44 had developed secondary progressive MS.
The mean number of cortical lesions at diagnosis was 6.6 in patients with secondary progressive MS at 20 years, which was significantly higher than the mean 1.3 cortical lesions in the other patients (P < .001).
In addition, post-hoc analysis showed that the median number of cortical lesions was significantly higher in patients with secondary progressive MS (6), compared with those with CIS (0; P < .001), relapsing-remitting MS (0; P < .001), and primary progressive MS (4.5; P = .013). Patients with primary progressive MS had a higher number of cortical lesions than patients with CIS and those with relapsing-remitting MS (P = .001).
The investigators also examined disability at 20 years. At that timepoint, mean EDSS score was 1.5 in patients with no cortical lesions, 3.0 in patients with 1 to 3 cortical lesions at baseline, and 6.0 in patients with more than 3 cortical lesions.
In a regression analysis, the number of cortical lesions and EDSS at diagnosis were the best predictors of long-term disability (P < .001). These factors explained about 57% of the variance in EDSS score after 20 years.
‘Important study’
“This important study supports that the presence of cortical lesions at the time of diagnosis is associated with long-term disability and transition to a secondary progressive disease course,” said Elias S. Sotirchos, MD, assistant professor of neurology at Johns Hopkins University, Baltimore. The study size and long duration of follow-up are important strengths of the findings, he added.
Still, further research is needed to validate cortical lesions as a biomarker in clinical practice. Aside from technical validation issues relating to the identification of cortical lesions, whether cortical lesion burden can be used to guide therapeutic decision-making in MS is not clear, said Dr. Sotirchos.
“Notably, these patients were diagnosed and enrolled in this study 20 years ago, prior to the availability of newer disease-modifying therapies [DMTs] that are more effective at preventing inflammatory disease activity in MS,” he said, referring to the participants in the current study.
While recent observational studies have suggested that early initiation of higher-efficacy disease-modifying therapies (DMTs) may reduce long-term disability and risk for transition to secondary progressive MS, the optimal approach to treatment in patients with a new diagnosis remains unclear, said Dr. Sotirchos.
Furthermore, it is unknown whether use of higher-efficacy DMTs may affect the risk of future disability in patients with high cortical lesion burden at baseline, said Dr. Sotirchos. “Or is it too late, especially considering the modest effects of DMTs in progressive patients and that cortical lesion burden was higher in patients that are progressive?”
One additional question to be addressed is how baseline cortical lesion burden adds to other factors that neurologists use in clinical practice to stratify patients’ risk of future disability, such as spinal cord involvement, motor or sphincter symptoms at onset, poor recovery from attacks, and white matter lesion burden, said Dr. Sotirchos.
The source of funding for this study was not reported. Dr. Schiavi and Dr. Sotirchos have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(MS), according to new research. Cortical lesions also may be an early marker of future disability accumulation.
In the study, patients who had developed secondary progressive MS after 20 years of follow-up had approximately 7 cortical lesions at baseline. This number was significantly higher than the baseline number of cortical lesions in patients with clinically isolated syndrome (CIS), relapsing-remitting MS, or primary progressive MS at 20 years.
“Our study represented a clear indication that the assessment, presence, and high number of cortical lesions at diagnosis is one of the tools at the disposal of the neurologist for the early identification of patients with more serious disease course,” said Gian Marco Schiavi, MD, a neurology resident at the University of Verona, Italy, during the presentation of his research.
The study was presented October 14 at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Accumulation of disability
Previous research has indicated that cortical lesions play a role in the accumulation of disability in MS and the conversion to secondary progressive MS. Other observations suggest that the number of cortical lesions after 30 years of follow-up explains more than 40% of the difference in disability between patients with secondary progressive MS.
The current investigators sought to understand whether cortical lesions at diagnosis could predict a patient’s risk for development of secondary progressive MS and risk for disability accumulation. They included 220 patients with MS and approximately 20 years of follow-up in their study.
At the time of diagnosis, all participants underwent 1.5-T MRI with double inversion recovery. Participants also presented for periodic MRI and clinical evaluations.
The researchers used analysis of variance to compare the baseline number of cortical lesions between patients with CIS, relapsing-remitting MS, secondary progressive MS, and primary progressive MS at 20 years. They also performed a multivariable regression analysis to predict patients’ final scores on the Expanded Disability Status Scale (EDSS). Variables included participants’ demographic, clinical, and radiological characteristics.
Lesions and disease progression
At baseline (the time of diagnosis), 162 patients had relapsing-remitting MS, 45 had CIS, and 12 had primary progressive MS. In all, 106 patients had no cortical lesions, 47 had 3 or fewer cortical lesions, and 67 had more than 3 cortical lesions.
At 20 years, 12 patients still had CIS, 152 had relapsing-remitting MS, and 44 had developed secondary progressive MS.
The mean number of cortical lesions at diagnosis was 6.6 in patients with secondary progressive MS at 20 years, which was significantly higher than the mean 1.3 cortical lesions in the other patients (P < .001).
In addition, post-hoc analysis showed that the median number of cortical lesions was significantly higher in patients with secondary progressive MS (6), compared with those with CIS (0; P < .001), relapsing-remitting MS (0; P < .001), and primary progressive MS (4.5; P = .013). Patients with primary progressive MS had a higher number of cortical lesions than patients with CIS and those with relapsing-remitting MS (P = .001).
The investigators also examined disability at 20 years. At that timepoint, mean EDSS score was 1.5 in patients with no cortical lesions, 3.0 in patients with 1 to 3 cortical lesions at baseline, and 6.0 in patients with more than 3 cortical lesions.
In a regression analysis, the number of cortical lesions and EDSS at diagnosis were the best predictors of long-term disability (P < .001). These factors explained about 57% of the variance in EDSS score after 20 years.
‘Important study’
“This important study supports that the presence of cortical lesions at the time of diagnosis is associated with long-term disability and transition to a secondary progressive disease course,” said Elias S. Sotirchos, MD, assistant professor of neurology at Johns Hopkins University, Baltimore. The study size and long duration of follow-up are important strengths of the findings, he added.
Still, further research is needed to validate cortical lesions as a biomarker in clinical practice. Aside from technical validation issues relating to the identification of cortical lesions, whether cortical lesion burden can be used to guide therapeutic decision-making in MS is not clear, said Dr. Sotirchos.
“Notably, these patients were diagnosed and enrolled in this study 20 years ago, prior to the availability of newer disease-modifying therapies [DMTs] that are more effective at preventing inflammatory disease activity in MS,” he said, referring to the participants in the current study.
While recent observational studies have suggested that early initiation of higher-efficacy disease-modifying therapies (DMTs) may reduce long-term disability and risk for transition to secondary progressive MS, the optimal approach to treatment in patients with a new diagnosis remains unclear, said Dr. Sotirchos.
Furthermore, it is unknown whether use of higher-efficacy DMTs may affect the risk of future disability in patients with high cortical lesion burden at baseline, said Dr. Sotirchos. “Or is it too late, especially considering the modest effects of DMTs in progressive patients and that cortical lesion burden was higher in patients that are progressive?”
One additional question to be addressed is how baseline cortical lesion burden adds to other factors that neurologists use in clinical practice to stratify patients’ risk of future disability, such as spinal cord involvement, motor or sphincter symptoms at onset, poor recovery from attacks, and white matter lesion burden, said Dr. Sotirchos.
The source of funding for this study was not reported. Dr. Schiavi and Dr. Sotirchos have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2021
Lumbar epidural steroid jab lowers bone formation in older women
Among postmenopausal women who received an epidural steroid injection (ESI) in the lumbar spine to treat back and leg pain arising from a compressed nerve in the spine, levels of bone formation biomarkers were decreased. The decrease in levels persisted more than 12 weeks, results from a new study show.
In addition, serum cortisol levels decreased by 50% at week 1 after the ESI, indicating systemic absorption of the steroid.
“The extent and duration of these effects suggest that patients who receive multiple [ESIs in the lumbar spine] may be at particular risk for harmful skeletal consequences,” Shannon Clare reported in an oral presentation at the annual meeting of the American Society for Bone and Mineral Research.
Further studies are needed of the relationship between these short-term changes in bone turnover and bone loss and the risk for fracture among the burgeoning population treated with ESIs, added Ms. Clare, of the Hospital for Special Surgery, New York.
The researchers examined changes in serum levels of bone formation and resorption markers and other analytes in 24 women who received a lumbar ESI for radicular back pain and in 8 other women from the hospital population who served as control persons.
Among the women who received ESI, 1 week after the injection, serum levels of two bone formation biomarkers – total procollagen type 1 N-terminal peptide (P1NP) and osteocalcin – were about 27% lower than at baseline. The suppression persisted beyond 12 weeks.
Serum levels of the bone resorption biomarker C-terminal telopeptide of type I collagen (CTX) did not differ significantly after ESI.
“Our results are notable because we found that the duration of suppression of bone formation extended beyond 12 weeks, a far longer duration than seen previously with intra-articular injections” of glucocorticoids, said Ms. Clare and senior author Emily M. Stein, MD, director of research for the Metabolic Bone Service and an endocrinologist at the Hospital for Special Surgery and is associate professor of medicine at Weill Cornell Medicine, both in New York.
The findings suggest that patients should not receive multiple doses within a 12-week period, they told this news organization in a joint email response.
Women are not typically screened for osteopenia or osteoporosis before ESI. However, “our results suggest that physicians should consider screening women for osteoporosis who receive ESI, particularly those who are treated with multiple doses,” said Ms. Clare and Dr. Stein. “Steroid exposure should be minimized as much as possible by having patients space injections as far as they can tolerate.”
Systemic absorption, negative impact on bone turnover markers
“The hypothesis that [ESIs] interfere with the vertebral osseous microenvironment and increase the risk of vertebral fractures has been supported with evidence in the literature,” Mohamad Bydon, MD, professor of neurosurgery, orthopedic surgery, and health services research at the Mayo Clinic, Rochester, Minn., said in an interview.
Prior studies have demonstrated a decrease in bone mineral density (BMD) and an increase in vertebral fractures following ESI, added Dr. Bydon, senior author of a 2018 review of the effect of ESI on BMD and vertebral fracture risk that was published in Pain Medicine. He was not involved with the current study.
“The article by Clare et al. provides evidence on the systemic absorption of glucocorticoids by demonstrating a drop in serum cortisol following ESI,” he noted. “The measurement of bone metabolism biomarkers offers molecular confirmation of clinical and radiological observations of previous studies” showing that ESI affects the vertebrae.
More than 9 million ESIs each year
Each year, more than 9 million ESIs are administered to patients in the United States to relieve radicular back and leg pain that may be caused by a herniated disc or spinal stenosis (a gradual narrowing of the open spaces in the spinal column, which is common in older adults), the researchers explained.
Some patients experience sufficient pain relief with ESIs. Others may not be eligible for surgery and may receive multiple ESIs annually for many years because they provide pain relief.
It is well established that oral and intravenous glucocorticoids profoundly suppress bone formation and transiently increase bone resorption, causing substantial bone loss and increased fracture risk within 3 months of administration, Ms. Clare explained in the session.
Long-term use of high-dose inhaled glucocorticoids has been associated with bone loss and fractures. However, the effect of ESIs on bone has been less well studied.
The researchers hypothesized that ESIs are systemically absorbed and cause suppression of bone formation without a compensatory decrease in bone resorption.
They enrolled 24 patients who had undergone lumbar ESIs and 8 control patients. The mean age of the patients in the two groups was 63 years and 68 years, respectively. Most patients were White (88% and 100%, respectively). The mean body mass index was 27 kg/m2 and 28 kg/m2, respectively. On average, the patients had entered menopause 12 and 16 years earlier, respectively.
In the group that received steroid injections, almost two-thirds (15 patients, 63%) received triamcinolone. The rest received dexamethasone (six patients, 25%) or betamethasone (three patients, 12%) at doses that were equivalent to 80 mg triamcinolone.
The patients’ baseline serum levels of 25-hydroxy vitamin D, parathyroid hormone, cortisol, P1NP, osteocalcin, and CTX were within the reference ranges and were similar in the two groups.
The researchers also determined serum levels of cortisol (to assess suppression of endogenous glucocorticoids), osteocalcin, P1NP, and CTX in the patients and control persons at 1, 4, 12, 26, and 52 weeks after patients had received the ESI.
The researchers acknowledged that the small sample is a study limitation. In addition, the first serum samples were taken 1 week after the injection, and so any earlier changes in analyte levels were not captured. The patients also received different types of steroids, although the doses were similar when converted to triamcinolone equivalents.
The study was supported by a Spine Service grant from the Hospital for Special Surgery. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among postmenopausal women who received an epidural steroid injection (ESI) in the lumbar spine to treat back and leg pain arising from a compressed nerve in the spine, levels of bone formation biomarkers were decreased. The decrease in levels persisted more than 12 weeks, results from a new study show.
In addition, serum cortisol levels decreased by 50% at week 1 after the ESI, indicating systemic absorption of the steroid.
“The extent and duration of these effects suggest that patients who receive multiple [ESIs in the lumbar spine] may be at particular risk for harmful skeletal consequences,” Shannon Clare reported in an oral presentation at the annual meeting of the American Society for Bone and Mineral Research.
Further studies are needed of the relationship between these short-term changes in bone turnover and bone loss and the risk for fracture among the burgeoning population treated with ESIs, added Ms. Clare, of the Hospital for Special Surgery, New York.
The researchers examined changes in serum levels of bone formation and resorption markers and other analytes in 24 women who received a lumbar ESI for radicular back pain and in 8 other women from the hospital population who served as control persons.
Among the women who received ESI, 1 week after the injection, serum levels of two bone formation biomarkers – total procollagen type 1 N-terminal peptide (P1NP) and osteocalcin – were about 27% lower than at baseline. The suppression persisted beyond 12 weeks.
Serum levels of the bone resorption biomarker C-terminal telopeptide of type I collagen (CTX) did not differ significantly after ESI.
“Our results are notable because we found that the duration of suppression of bone formation extended beyond 12 weeks, a far longer duration than seen previously with intra-articular injections” of glucocorticoids, said Ms. Clare and senior author Emily M. Stein, MD, director of research for the Metabolic Bone Service and an endocrinologist at the Hospital for Special Surgery and is associate professor of medicine at Weill Cornell Medicine, both in New York.
The findings suggest that patients should not receive multiple doses within a 12-week period, they told this news organization in a joint email response.
Women are not typically screened for osteopenia or osteoporosis before ESI. However, “our results suggest that physicians should consider screening women for osteoporosis who receive ESI, particularly those who are treated with multiple doses,” said Ms. Clare and Dr. Stein. “Steroid exposure should be minimized as much as possible by having patients space injections as far as they can tolerate.”
Systemic absorption, negative impact on bone turnover markers
“The hypothesis that [ESIs] interfere with the vertebral osseous microenvironment and increase the risk of vertebral fractures has been supported with evidence in the literature,” Mohamad Bydon, MD, professor of neurosurgery, orthopedic surgery, and health services research at the Mayo Clinic, Rochester, Minn., said in an interview.
Prior studies have demonstrated a decrease in bone mineral density (BMD) and an increase in vertebral fractures following ESI, added Dr. Bydon, senior author of a 2018 review of the effect of ESI on BMD and vertebral fracture risk that was published in Pain Medicine. He was not involved with the current study.
“The article by Clare et al. provides evidence on the systemic absorption of glucocorticoids by demonstrating a drop in serum cortisol following ESI,” he noted. “The measurement of bone metabolism biomarkers offers molecular confirmation of clinical and radiological observations of previous studies” showing that ESI affects the vertebrae.
More than 9 million ESIs each year
Each year, more than 9 million ESIs are administered to patients in the United States to relieve radicular back and leg pain that may be caused by a herniated disc or spinal stenosis (a gradual narrowing of the open spaces in the spinal column, which is common in older adults), the researchers explained.
Some patients experience sufficient pain relief with ESIs. Others may not be eligible for surgery and may receive multiple ESIs annually for many years because they provide pain relief.
It is well established that oral and intravenous glucocorticoids profoundly suppress bone formation and transiently increase bone resorption, causing substantial bone loss and increased fracture risk within 3 months of administration, Ms. Clare explained in the session.
Long-term use of high-dose inhaled glucocorticoids has been associated with bone loss and fractures. However, the effect of ESIs on bone has been less well studied.
The researchers hypothesized that ESIs are systemically absorbed and cause suppression of bone formation without a compensatory decrease in bone resorption.
They enrolled 24 patients who had undergone lumbar ESIs and 8 control patients. The mean age of the patients in the two groups was 63 years and 68 years, respectively. Most patients were White (88% and 100%, respectively). The mean body mass index was 27 kg/m2 and 28 kg/m2, respectively. On average, the patients had entered menopause 12 and 16 years earlier, respectively.
In the group that received steroid injections, almost two-thirds (15 patients, 63%) received triamcinolone. The rest received dexamethasone (six patients, 25%) or betamethasone (three patients, 12%) at doses that were equivalent to 80 mg triamcinolone.
The patients’ baseline serum levels of 25-hydroxy vitamin D, parathyroid hormone, cortisol, P1NP, osteocalcin, and CTX were within the reference ranges and were similar in the two groups.
The researchers also determined serum levels of cortisol (to assess suppression of endogenous glucocorticoids), osteocalcin, P1NP, and CTX in the patients and control persons at 1, 4, 12, 26, and 52 weeks after patients had received the ESI.
The researchers acknowledged that the small sample is a study limitation. In addition, the first serum samples were taken 1 week after the injection, and so any earlier changes in analyte levels were not captured. The patients also received different types of steroids, although the doses were similar when converted to triamcinolone equivalents.
The study was supported by a Spine Service grant from the Hospital for Special Surgery. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among postmenopausal women who received an epidural steroid injection (ESI) in the lumbar spine to treat back and leg pain arising from a compressed nerve in the spine, levels of bone formation biomarkers were decreased. The decrease in levels persisted more than 12 weeks, results from a new study show.
In addition, serum cortisol levels decreased by 50% at week 1 after the ESI, indicating systemic absorption of the steroid.
“The extent and duration of these effects suggest that patients who receive multiple [ESIs in the lumbar spine] may be at particular risk for harmful skeletal consequences,” Shannon Clare reported in an oral presentation at the annual meeting of the American Society for Bone and Mineral Research.
Further studies are needed of the relationship between these short-term changes in bone turnover and bone loss and the risk for fracture among the burgeoning population treated with ESIs, added Ms. Clare, of the Hospital for Special Surgery, New York.
The researchers examined changes in serum levels of bone formation and resorption markers and other analytes in 24 women who received a lumbar ESI for radicular back pain and in 8 other women from the hospital population who served as control persons.
Among the women who received ESI, 1 week after the injection, serum levels of two bone formation biomarkers – total procollagen type 1 N-terminal peptide (P1NP) and osteocalcin – were about 27% lower than at baseline. The suppression persisted beyond 12 weeks.
Serum levels of the bone resorption biomarker C-terminal telopeptide of type I collagen (CTX) did not differ significantly after ESI.
“Our results are notable because we found that the duration of suppression of bone formation extended beyond 12 weeks, a far longer duration than seen previously with intra-articular injections” of glucocorticoids, said Ms. Clare and senior author Emily M. Stein, MD, director of research for the Metabolic Bone Service and an endocrinologist at the Hospital for Special Surgery and is associate professor of medicine at Weill Cornell Medicine, both in New York.
The findings suggest that patients should not receive multiple doses within a 12-week period, they told this news organization in a joint email response.
Women are not typically screened for osteopenia or osteoporosis before ESI. However, “our results suggest that physicians should consider screening women for osteoporosis who receive ESI, particularly those who are treated with multiple doses,” said Ms. Clare and Dr. Stein. “Steroid exposure should be minimized as much as possible by having patients space injections as far as they can tolerate.”
Systemic absorption, negative impact on bone turnover markers
“The hypothesis that [ESIs] interfere with the vertebral osseous microenvironment and increase the risk of vertebral fractures has been supported with evidence in the literature,” Mohamad Bydon, MD, professor of neurosurgery, orthopedic surgery, and health services research at the Mayo Clinic, Rochester, Minn., said in an interview.
Prior studies have demonstrated a decrease in bone mineral density (BMD) and an increase in vertebral fractures following ESI, added Dr. Bydon, senior author of a 2018 review of the effect of ESI on BMD and vertebral fracture risk that was published in Pain Medicine. He was not involved with the current study.
“The article by Clare et al. provides evidence on the systemic absorption of glucocorticoids by demonstrating a drop in serum cortisol following ESI,” he noted. “The measurement of bone metabolism biomarkers offers molecular confirmation of clinical and radiological observations of previous studies” showing that ESI affects the vertebrae.
More than 9 million ESIs each year
Each year, more than 9 million ESIs are administered to patients in the United States to relieve radicular back and leg pain that may be caused by a herniated disc or spinal stenosis (a gradual narrowing of the open spaces in the spinal column, which is common in older adults), the researchers explained.
Some patients experience sufficient pain relief with ESIs. Others may not be eligible for surgery and may receive multiple ESIs annually for many years because they provide pain relief.
It is well established that oral and intravenous glucocorticoids profoundly suppress bone formation and transiently increase bone resorption, causing substantial bone loss and increased fracture risk within 3 months of administration, Ms. Clare explained in the session.
Long-term use of high-dose inhaled glucocorticoids has been associated with bone loss and fractures. However, the effect of ESIs on bone has been less well studied.
The researchers hypothesized that ESIs are systemically absorbed and cause suppression of bone formation without a compensatory decrease in bone resorption.
They enrolled 24 patients who had undergone lumbar ESIs and 8 control patients. The mean age of the patients in the two groups was 63 years and 68 years, respectively. Most patients were White (88% and 100%, respectively). The mean body mass index was 27 kg/m2 and 28 kg/m2, respectively. On average, the patients had entered menopause 12 and 16 years earlier, respectively.
In the group that received steroid injections, almost two-thirds (15 patients, 63%) received triamcinolone. The rest received dexamethasone (six patients, 25%) or betamethasone (three patients, 12%) at doses that were equivalent to 80 mg triamcinolone.
The patients’ baseline serum levels of 25-hydroxy vitamin D, parathyroid hormone, cortisol, P1NP, osteocalcin, and CTX were within the reference ranges and were similar in the two groups.
The researchers also determined serum levels of cortisol (to assess suppression of endogenous glucocorticoids), osteocalcin, P1NP, and CTX in the patients and control persons at 1, 4, 12, 26, and 52 weeks after patients had received the ESI.
The researchers acknowledged that the small sample is a study limitation. In addition, the first serum samples were taken 1 week after the injection, and so any earlier changes in analyte levels were not captured. The patients also received different types of steroids, although the doses were similar when converted to triamcinolone equivalents.
The study was supported by a Spine Service grant from the Hospital for Special Surgery. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Melatonin improves sleep in MS
according to a new pilot study.
The study included only 30 patients, but the findings suggest that melatonin could potentially help patients with MS who have sleep issues, according to Wan-Yu Hsu, PhD, who presented the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
There is no optimal management of sleep issues for these patients, and objective studies of sleep in patients with MS are scarce, said Dr. Hsu, who is an associate specialist in the department of neurology at the University of California, San Francisco. She worked with Riley Bove, MD, who is an associate professor of neurology at UCSF Weill Institute for Neurosciences.
“Melatonin use was associated with improvement in sleep quality and sleep disturbance in MS patients, although there was no significant change in other outcomes, like daytime sleepiness, mood, and walking ability” Dr. Hsu said in an interview.
Melatonin is inexpensive and readily available over the counter, but it’s too soon to begin recommending it to MS patients experiencing sleep problems, according to Dr. Hsu. “It’s a good start that we’re seeing some effects here with this relatively small group of people. Larger studies are needed to unravel the complex relationship between MS and sleep disturbances, as well as develop successful interventions. But for now, since melatonin is an over-the-counter, low-cost supplement, many patients are trying it already.”
Melatonin regulates the sleep-wake cycle, and previous research has shown a decrease in melatonin serum levels as a result of corticosteroid administration. Other work has suggested that the decline of melatonin secretion in MS may reflect progressive failure of the pineal gland in the pathogenesis of MS. “The cause of sleep problems can be lesions and neural damage to brain structures involved in sleep, or symptoms that indirectly disrupt sleep,” she said.
Indeed, sleep issues in MS are common and wide-ranging, according to Mark Gudesblatt, MD, who was asked to comment on the study. His group previously reported that 65% of people with MS who reported fatigue had undiagnosed obstructive sleep apnea. He also pointed out that disruption of the neural network also disrupts sleep. “That is not only sleep-disordered breathing, that’s sleep onset, REM latency, and sleep efficiency,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y.
Dr. Gudesblatt cautioned that melatonin, as a dietary supplement, is unregulated. The potency listed on the package may not be accurate and also may not be the correct dose for the patient. “It’s fraught with problems, but ultimately it’s relatively safe,” said Dr. Gudesblatt.
The study was a double-blind, placebo-controlled, crossover study. Participants had a Pittsburgh Sleep Quality Index (PSQI) score of 5 or more, or an Insomnia Severity Index (ISI) score higher than 14 at baseline. Other baseline assessments included patient-reported outcomes for sleep disturbances, sleep quality, daytime sleepiness, fatigue, walking ability, and mood. Half of the participants received melatonin for the first 2 weeks and then switched to placebo. The other half started with placebo and moved over to melatonin at the beginning of week 3.
Participants in the trial started out at 0.5 mg melatonin and were stepped up to 3.0 mg after 3 days if they didn't feel it was working, both when taking melatonin and when taking placebo. Of the 30 patients, 24 stepped up to 3.0 mg when they were receiving melatonin.*
During the second and fourth weeks, participants wore an actigraph watch to measure their physical and sleep activities, and then repeated the patient-reported outcome measures at the end of weeks 2 and 4. Melatonin improved average sleep time (6.96 vs. 6.67 hours; P = .03) as measured by the actigraph watch. Sleep efficiency was also nominally improved (84.7% vs. 83.2%), though the result was not statistically significant (P = .07). Other trends toward statistical significance included improvements in ISI (–3.5 vs. –2.4; P = .07), change in PSQI component 1 (–0.03 vs. 0.0; P = .07), and change in the NeuroQoL-Fatigue score (–4.7 vs. –2.4; P = .06).
Dr. Hsu hopes to conduct larger studies to examine how the disease-modifying therapies might affect the results of the study.
The study was funded by the National Multiple Sclerosis Society. Dr. Hsu and Dr. Gudesblatt have no relevant financial disclosures.
*This article was updated on Oct. 15.
according to a new pilot study.
The study included only 30 patients, but the findings suggest that melatonin could potentially help patients with MS who have sleep issues, according to Wan-Yu Hsu, PhD, who presented the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
There is no optimal management of sleep issues for these patients, and objective studies of sleep in patients with MS are scarce, said Dr. Hsu, who is an associate specialist in the department of neurology at the University of California, San Francisco. She worked with Riley Bove, MD, who is an associate professor of neurology at UCSF Weill Institute for Neurosciences.
“Melatonin use was associated with improvement in sleep quality and sleep disturbance in MS patients, although there was no significant change in other outcomes, like daytime sleepiness, mood, and walking ability” Dr. Hsu said in an interview.
Melatonin is inexpensive and readily available over the counter, but it’s too soon to begin recommending it to MS patients experiencing sleep problems, according to Dr. Hsu. “It’s a good start that we’re seeing some effects here with this relatively small group of people. Larger studies are needed to unravel the complex relationship between MS and sleep disturbances, as well as develop successful interventions. But for now, since melatonin is an over-the-counter, low-cost supplement, many patients are trying it already.”
Melatonin regulates the sleep-wake cycle, and previous research has shown a decrease in melatonin serum levels as a result of corticosteroid administration. Other work has suggested that the decline of melatonin secretion in MS may reflect progressive failure of the pineal gland in the pathogenesis of MS. “The cause of sleep problems can be lesions and neural damage to brain structures involved in sleep, or symptoms that indirectly disrupt sleep,” she said.
Indeed, sleep issues in MS are common and wide-ranging, according to Mark Gudesblatt, MD, who was asked to comment on the study. His group previously reported that 65% of people with MS who reported fatigue had undiagnosed obstructive sleep apnea. He also pointed out that disruption of the neural network also disrupts sleep. “That is not only sleep-disordered breathing, that’s sleep onset, REM latency, and sleep efficiency,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y.
Dr. Gudesblatt cautioned that melatonin, as a dietary supplement, is unregulated. The potency listed on the package may not be accurate and also may not be the correct dose for the patient. “It’s fraught with problems, but ultimately it’s relatively safe,” said Dr. Gudesblatt.
The study was a double-blind, placebo-controlled, crossover study. Participants had a Pittsburgh Sleep Quality Index (PSQI) score of 5 or more, or an Insomnia Severity Index (ISI) score higher than 14 at baseline. Other baseline assessments included patient-reported outcomes for sleep disturbances, sleep quality, daytime sleepiness, fatigue, walking ability, and mood. Half of the participants received melatonin for the first 2 weeks and then switched to placebo. The other half started with placebo and moved over to melatonin at the beginning of week 3.
Participants in the trial started out at 0.5 mg melatonin and were stepped up to 3.0 mg after 3 days if they didn't feel it was working, both when taking melatonin and when taking placebo. Of the 30 patients, 24 stepped up to 3.0 mg when they were receiving melatonin.*
During the second and fourth weeks, participants wore an actigraph watch to measure their physical and sleep activities, and then repeated the patient-reported outcome measures at the end of weeks 2 and 4. Melatonin improved average sleep time (6.96 vs. 6.67 hours; P = .03) as measured by the actigraph watch. Sleep efficiency was also nominally improved (84.7% vs. 83.2%), though the result was not statistically significant (P = .07). Other trends toward statistical significance included improvements in ISI (–3.5 vs. –2.4; P = .07), change in PSQI component 1 (–0.03 vs. 0.0; P = .07), and change in the NeuroQoL-Fatigue score (–4.7 vs. –2.4; P = .06).
Dr. Hsu hopes to conduct larger studies to examine how the disease-modifying therapies might affect the results of the study.
The study was funded by the National Multiple Sclerosis Society. Dr. Hsu and Dr. Gudesblatt have no relevant financial disclosures.
*This article was updated on Oct. 15.
according to a new pilot study.
The study included only 30 patients, but the findings suggest that melatonin could potentially help patients with MS who have sleep issues, according to Wan-Yu Hsu, PhD, who presented the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
There is no optimal management of sleep issues for these patients, and objective studies of sleep in patients with MS are scarce, said Dr. Hsu, who is an associate specialist in the department of neurology at the University of California, San Francisco. She worked with Riley Bove, MD, who is an associate professor of neurology at UCSF Weill Institute for Neurosciences.
“Melatonin use was associated with improvement in sleep quality and sleep disturbance in MS patients, although there was no significant change in other outcomes, like daytime sleepiness, mood, and walking ability” Dr. Hsu said in an interview.
Melatonin is inexpensive and readily available over the counter, but it’s too soon to begin recommending it to MS patients experiencing sleep problems, according to Dr. Hsu. “It’s a good start that we’re seeing some effects here with this relatively small group of people. Larger studies are needed to unravel the complex relationship between MS and sleep disturbances, as well as develop successful interventions. But for now, since melatonin is an over-the-counter, low-cost supplement, many patients are trying it already.”
Melatonin regulates the sleep-wake cycle, and previous research has shown a decrease in melatonin serum levels as a result of corticosteroid administration. Other work has suggested that the decline of melatonin secretion in MS may reflect progressive failure of the pineal gland in the pathogenesis of MS. “The cause of sleep problems can be lesions and neural damage to brain structures involved in sleep, or symptoms that indirectly disrupt sleep,” she said.
Indeed, sleep issues in MS are common and wide-ranging, according to Mark Gudesblatt, MD, who was asked to comment on the study. His group previously reported that 65% of people with MS who reported fatigue had undiagnosed obstructive sleep apnea. He also pointed out that disruption of the neural network also disrupts sleep. “That is not only sleep-disordered breathing, that’s sleep onset, REM latency, and sleep efficiency,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y.
Dr. Gudesblatt cautioned that melatonin, as a dietary supplement, is unregulated. The potency listed on the package may not be accurate and also may not be the correct dose for the patient. “It’s fraught with problems, but ultimately it’s relatively safe,” said Dr. Gudesblatt.
The study was a double-blind, placebo-controlled, crossover study. Participants had a Pittsburgh Sleep Quality Index (PSQI) score of 5 or more, or an Insomnia Severity Index (ISI) score higher than 14 at baseline. Other baseline assessments included patient-reported outcomes for sleep disturbances, sleep quality, daytime sleepiness, fatigue, walking ability, and mood. Half of the participants received melatonin for the first 2 weeks and then switched to placebo. The other half started with placebo and moved over to melatonin at the beginning of week 3.
Participants in the trial started out at 0.5 mg melatonin and were stepped up to 3.0 mg after 3 days if they didn't feel it was working, both when taking melatonin and when taking placebo. Of the 30 patients, 24 stepped up to 3.0 mg when they were receiving melatonin.*
During the second and fourth weeks, participants wore an actigraph watch to measure their physical and sleep activities, and then repeated the patient-reported outcome measures at the end of weeks 2 and 4. Melatonin improved average sleep time (6.96 vs. 6.67 hours; P = .03) as measured by the actigraph watch. Sleep efficiency was also nominally improved (84.7% vs. 83.2%), though the result was not statistically significant (P = .07). Other trends toward statistical significance included improvements in ISI (–3.5 vs. –2.4; P = .07), change in PSQI component 1 (–0.03 vs. 0.0; P = .07), and change in the NeuroQoL-Fatigue score (–4.7 vs. –2.4; P = .06).
Dr. Hsu hopes to conduct larger studies to examine how the disease-modifying therapies might affect the results of the study.
The study was funded by the National Multiple Sclerosis Society. Dr. Hsu and Dr. Gudesblatt have no relevant financial disclosures.
*This article was updated on Oct. 15.
FROM ECTRIMS 2021
Kids in foster care get psychotropic meds at ‘alarming’ rates
Children in foster care are far more likely to be prescribed psychotropic medication, compared with children who are not in foster care, an analysis of Medicaid claims data shows.
Different rates of mental health disorders in these groups do not fully explain the “alarming trend,” which persists across psychotropic medication classes, said study author Rachael J. Keefe, MD, MPH.
Dr. Keefe, with Baylor College of Medicine, Houston, and colleagues analyzed Medicaid claims data from two managed care organizations to compare the prevalence of psychotropic medication use among children in foster care versus children insured by Medicaid but not in foster care. The study focused on claims from the same region in southeast Texas between July 2014 and June 2016.
The researchers included 388,914 children in Medicaid and 8,426 children in foster care in their analysis. They excluded children with a seizure or epilepsy diagnosis.
About 8% of children not in foster care received psychotropic medications, compared with 35% of those in foster care.
Children in foster care were 27 times more likely to receive antipsychotic medication (21.2% of children in foster care vs. 0.8% of children not in foster care) and twice as likely to receive antianxiety medication (6% vs. 3%).
For children in foster care, the rate of alpha-agonist use was 15 times higher, the rate of antidepressant use was 13 times higher, the rate of mood stabilizer use was 26 times higher, and the rate of stimulant use was 6 times higher.
The researchers have a limited understanding of the full context in which these medications were prescribed, and psychotropic medications have a role in the treatment of children in foster care, Dr. Keefe acknowledged.
“We have to be careful not to have a knee-jerk reaction” and inappropriately withhold medication from children in foster care, she said in an interview.
But overprescribing has been a concern. Dr. Keefe leads a foster care clinical service at Texas Children’s Hospital in Houston.
“The overprescribing of psychotropic medications to children in foster care is something I feel every day in my clinical practice, but it’s different to see it on paper,” Dr. Keefe said in a news release highlighting the research, which she presented on Oct. 11 at the annual meeting of the American Academy of Pediatrics. “It’s especially shocking to see these dramatic differences in children of preschool and elementary age.”
Misdiagnosis can be a common problem among children in foster care, said Danielle Shaw, MD, a child and adolescent psychiatrist in Camarillo, Calif., during a question-and-answer period following the presentation.
“I see incorrect diagnoses very frequently,” Dr. Shaw said. “The history of trauma or [adverse childhood experiences] is not even included in the assessment. Mood lability from trauma is misdiagnosed as bipolar disorder, despite not meeting criteria. This will justify the use of antipsychotic medication and mood stabilizers. Flashbacks can be mistaken for a psychotic disorder, which again justifies the use of antipsychotic medication.”
Children in foster care have experienced numerous traumatic experiences that affect brain development and the hypothalamic-pituitary-adrenal axis, Dr. Keefe said.
“Although from previous research we know that children in foster care are more likely to carry mental health and developmental disorder diagnoses, this does not account for the significant difference in prescribing practices in this population,” Dr. Keefe said in an interview.
Although the study focused on data in Texas, Dr. Keefe expects similar patterns exist in other regions, based on anecdotal reports. “I work with foster care pediatricians across the country, and many have seen similar concerning trends within their own clinical practices,” she said.
The use of appropriate therapies, minimizing transitions between providers, improved record keeping, the development of deprescribing algorithms, and placement of children in foster care in long-term homes as early as possible are measures that potentially could reduce inappropriate psychotropic prescribing for children in foster care, Dr. Keefe suggested.
The research was funded by a Texas Medical Center Health Policy Research Grant. The study authors and Dr. Shaw had no relevant financial disclosures.
Children in foster care are far more likely to be prescribed psychotropic medication, compared with children who are not in foster care, an analysis of Medicaid claims data shows.
Different rates of mental health disorders in these groups do not fully explain the “alarming trend,” which persists across psychotropic medication classes, said study author Rachael J. Keefe, MD, MPH.
Dr. Keefe, with Baylor College of Medicine, Houston, and colleagues analyzed Medicaid claims data from two managed care organizations to compare the prevalence of psychotropic medication use among children in foster care versus children insured by Medicaid but not in foster care. The study focused on claims from the same region in southeast Texas between July 2014 and June 2016.
The researchers included 388,914 children in Medicaid and 8,426 children in foster care in their analysis. They excluded children with a seizure or epilepsy diagnosis.
About 8% of children not in foster care received psychotropic medications, compared with 35% of those in foster care.
Children in foster care were 27 times more likely to receive antipsychotic medication (21.2% of children in foster care vs. 0.8% of children not in foster care) and twice as likely to receive antianxiety medication (6% vs. 3%).
For children in foster care, the rate of alpha-agonist use was 15 times higher, the rate of antidepressant use was 13 times higher, the rate of mood stabilizer use was 26 times higher, and the rate of stimulant use was 6 times higher.
The researchers have a limited understanding of the full context in which these medications were prescribed, and psychotropic medications have a role in the treatment of children in foster care, Dr. Keefe acknowledged.
“We have to be careful not to have a knee-jerk reaction” and inappropriately withhold medication from children in foster care, she said in an interview.
But overprescribing has been a concern. Dr. Keefe leads a foster care clinical service at Texas Children’s Hospital in Houston.
“The overprescribing of psychotropic medications to children in foster care is something I feel every day in my clinical practice, but it’s different to see it on paper,” Dr. Keefe said in a news release highlighting the research, which she presented on Oct. 11 at the annual meeting of the American Academy of Pediatrics. “It’s especially shocking to see these dramatic differences in children of preschool and elementary age.”
Misdiagnosis can be a common problem among children in foster care, said Danielle Shaw, MD, a child and adolescent psychiatrist in Camarillo, Calif., during a question-and-answer period following the presentation.
“I see incorrect diagnoses very frequently,” Dr. Shaw said. “The history of trauma or [adverse childhood experiences] is not even included in the assessment. Mood lability from trauma is misdiagnosed as bipolar disorder, despite not meeting criteria. This will justify the use of antipsychotic medication and mood stabilizers. Flashbacks can be mistaken for a psychotic disorder, which again justifies the use of antipsychotic medication.”
Children in foster care have experienced numerous traumatic experiences that affect brain development and the hypothalamic-pituitary-adrenal axis, Dr. Keefe said.
“Although from previous research we know that children in foster care are more likely to carry mental health and developmental disorder diagnoses, this does not account for the significant difference in prescribing practices in this population,” Dr. Keefe said in an interview.
Although the study focused on data in Texas, Dr. Keefe expects similar patterns exist in other regions, based on anecdotal reports. “I work with foster care pediatricians across the country, and many have seen similar concerning trends within their own clinical practices,” she said.
The use of appropriate therapies, minimizing transitions between providers, improved record keeping, the development of deprescribing algorithms, and placement of children in foster care in long-term homes as early as possible are measures that potentially could reduce inappropriate psychotropic prescribing for children in foster care, Dr. Keefe suggested.
The research was funded by a Texas Medical Center Health Policy Research Grant. The study authors and Dr. Shaw had no relevant financial disclosures.
Children in foster care are far more likely to be prescribed psychotropic medication, compared with children who are not in foster care, an analysis of Medicaid claims data shows.
Different rates of mental health disorders in these groups do not fully explain the “alarming trend,” which persists across psychotropic medication classes, said study author Rachael J. Keefe, MD, MPH.
Dr. Keefe, with Baylor College of Medicine, Houston, and colleagues analyzed Medicaid claims data from two managed care organizations to compare the prevalence of psychotropic medication use among children in foster care versus children insured by Medicaid but not in foster care. The study focused on claims from the same region in southeast Texas between July 2014 and June 2016.
The researchers included 388,914 children in Medicaid and 8,426 children in foster care in their analysis. They excluded children with a seizure or epilepsy diagnosis.
About 8% of children not in foster care received psychotropic medications, compared with 35% of those in foster care.
Children in foster care were 27 times more likely to receive antipsychotic medication (21.2% of children in foster care vs. 0.8% of children not in foster care) and twice as likely to receive antianxiety medication (6% vs. 3%).
For children in foster care, the rate of alpha-agonist use was 15 times higher, the rate of antidepressant use was 13 times higher, the rate of mood stabilizer use was 26 times higher, and the rate of stimulant use was 6 times higher.
The researchers have a limited understanding of the full context in which these medications were prescribed, and psychotropic medications have a role in the treatment of children in foster care, Dr. Keefe acknowledged.
“We have to be careful not to have a knee-jerk reaction” and inappropriately withhold medication from children in foster care, she said in an interview.
But overprescribing has been a concern. Dr. Keefe leads a foster care clinical service at Texas Children’s Hospital in Houston.
“The overprescribing of psychotropic medications to children in foster care is something I feel every day in my clinical practice, but it’s different to see it on paper,” Dr. Keefe said in a news release highlighting the research, which she presented on Oct. 11 at the annual meeting of the American Academy of Pediatrics. “It’s especially shocking to see these dramatic differences in children of preschool and elementary age.”
Misdiagnosis can be a common problem among children in foster care, said Danielle Shaw, MD, a child and adolescent psychiatrist in Camarillo, Calif., during a question-and-answer period following the presentation.
“I see incorrect diagnoses very frequently,” Dr. Shaw said. “The history of trauma or [adverse childhood experiences] is not even included in the assessment. Mood lability from trauma is misdiagnosed as bipolar disorder, despite not meeting criteria. This will justify the use of antipsychotic medication and mood stabilizers. Flashbacks can be mistaken for a psychotic disorder, which again justifies the use of antipsychotic medication.”
Children in foster care have experienced numerous traumatic experiences that affect brain development and the hypothalamic-pituitary-adrenal axis, Dr. Keefe said.
“Although from previous research we know that children in foster care are more likely to carry mental health and developmental disorder diagnoses, this does not account for the significant difference in prescribing practices in this population,” Dr. Keefe said in an interview.
Although the study focused on data in Texas, Dr. Keefe expects similar patterns exist in other regions, based on anecdotal reports. “I work with foster care pediatricians across the country, and many have seen similar concerning trends within their own clinical practices,” she said.
The use of appropriate therapies, minimizing transitions between providers, improved record keeping, the development of deprescribing algorithms, and placement of children in foster care in long-term homes as early as possible are measures that potentially could reduce inappropriate psychotropic prescribing for children in foster care, Dr. Keefe suggested.
The research was funded by a Texas Medical Center Health Policy Research Grant. The study authors and Dr. Shaw had no relevant financial disclosures.
FROM AAP 2021
Pandemic survey: Forty-six percent of pediatric headache patients got worse
, a newly released survey finds. But some actually found the pandemic era to be less stressful since they were tightly wound and could more easily control their home environments, a researcher said.
“We need to be very mindful of the connections between school and home environments – and social situations – and how they impact headache frequency,” said Marc DiSabella, DO, a pediatric neurologist at Children’s National Hospital/George Washington University, Washington. He is coauthor of a poster presented at the 50th annual meeting of the Child Neurology Society.
Dr. DiSabella and colleagues launched the survey to understand what headache patients were experiencing during the pandemic. They expected that “things were going to go really terrible in terms of headaches – or things would go great, and then things would crash when we had to reintegrate into society,” he said in an interview.
The team surveyed 113 pediatric patients who were evaluated at the hospital’s headache clinic between summer 2020 and winter 2021. Most of the patients were female (60%) and were aged 12-17 years (63%). Twenty-one percent were younger than 12 and 16% were older than 17. Chronic migraine (37%) was the most common diagnosis, followed by migraine with aura (22%), migraine without aura (19%), and new daily persistent headache (15%).
Nearly half (46%) of patients said their headaches had worsened during the pandemic. Many also reported more anxiety (55%), worsened mood (48%) and more stress (55%).
Dr. DiSabella said it’s especially notable that nearly two-thirds of those surveyed reported they were exercising less during the pandemic. Research has suggested that exercise and proper diet/sleep are crucial to improving headaches in kids, he said, and the survey findings suggest that exercise may be especially important. “Engaging in physical activity changes their pain threshold,” he said.
The researchers also reported that 60% of those surveyed said they looked at screens more than 6 hours per day. According to Dr. DiSabella, high screen use may not be worrisome from a headache perspective. “We have another study in publication that shows there’s not a clear association between frequency of screen use and headache intensity,” he said.
The survey doesn’t examine what has happened in recent weeks as schools have reopened. Anecdotally, Dr. DiSabella said some patients with migraine are feeling the stress of returning to normal routines. “They tend to be type A perfectionists and do well when they’re in control of their environment,” he said. “Now they’ve lost the control they had at home and are being put back into a stressful environment.”
Pandemic effects mixed
Commenting on the study, child neurologist Andrew D. Hershey, MD, PhD, of Cincinnati Children’s Hospital Medical Center, questioned the finding that many children suffered from more headaches during the pandemic. In his experience, “headaches were overall better when [children] were doing virtual learning,” he said in an interview. “We had fewer admissions, ED visits declined, and patients were maintaining better healthy habits. Some did express anxiety about not seeing friends, but were accommodating by doing this remotely.”
He added: “Since their return, kids are back to the same sleep deprivation issue since schools start too early, and they have more difficulty treating headaches acutely since they have to go to the nurse’s office [to do so]. They self-report a higher degree of stress and anxiety.”
On the other hand, Jack Gladstein, MD, a child neurologist at the University of Maryland, Baltimore, said in an interview that most of his patients suffered more headaches during the pandemic, although a small number with social anxiety thrived because they got to stay at home.
He agreed with Dr. DiSabella about the value of exercise. “At every visit we remind our youngsters with migraine to eat breakfast, exercise, get regular sleep, and drink fluids,” he said.
No study funding was reported. The study authors, Dr. Hershey, and Dr. Gladstein reported no disclosures.
, a newly released survey finds. But some actually found the pandemic era to be less stressful since they were tightly wound and could more easily control their home environments, a researcher said.
“We need to be very mindful of the connections between school and home environments – and social situations – and how they impact headache frequency,” said Marc DiSabella, DO, a pediatric neurologist at Children’s National Hospital/George Washington University, Washington. He is coauthor of a poster presented at the 50th annual meeting of the Child Neurology Society.
Dr. DiSabella and colleagues launched the survey to understand what headache patients were experiencing during the pandemic. They expected that “things were going to go really terrible in terms of headaches – or things would go great, and then things would crash when we had to reintegrate into society,” he said in an interview.
The team surveyed 113 pediatric patients who were evaluated at the hospital’s headache clinic between summer 2020 and winter 2021. Most of the patients were female (60%) and were aged 12-17 years (63%). Twenty-one percent were younger than 12 and 16% were older than 17. Chronic migraine (37%) was the most common diagnosis, followed by migraine with aura (22%), migraine without aura (19%), and new daily persistent headache (15%).
Nearly half (46%) of patients said their headaches had worsened during the pandemic. Many also reported more anxiety (55%), worsened mood (48%) and more stress (55%).
Dr. DiSabella said it’s especially notable that nearly two-thirds of those surveyed reported they were exercising less during the pandemic. Research has suggested that exercise and proper diet/sleep are crucial to improving headaches in kids, he said, and the survey findings suggest that exercise may be especially important. “Engaging in physical activity changes their pain threshold,” he said.
The researchers also reported that 60% of those surveyed said they looked at screens more than 6 hours per day. According to Dr. DiSabella, high screen use may not be worrisome from a headache perspective. “We have another study in publication that shows there’s not a clear association between frequency of screen use and headache intensity,” he said.
The survey doesn’t examine what has happened in recent weeks as schools have reopened. Anecdotally, Dr. DiSabella said some patients with migraine are feeling the stress of returning to normal routines. “They tend to be type A perfectionists and do well when they’re in control of their environment,” he said. “Now they’ve lost the control they had at home and are being put back into a stressful environment.”
Pandemic effects mixed
Commenting on the study, child neurologist Andrew D. Hershey, MD, PhD, of Cincinnati Children’s Hospital Medical Center, questioned the finding that many children suffered from more headaches during the pandemic. In his experience, “headaches were overall better when [children] were doing virtual learning,” he said in an interview. “We had fewer admissions, ED visits declined, and patients were maintaining better healthy habits. Some did express anxiety about not seeing friends, but were accommodating by doing this remotely.”
He added: “Since their return, kids are back to the same sleep deprivation issue since schools start too early, and they have more difficulty treating headaches acutely since they have to go to the nurse’s office [to do so]. They self-report a higher degree of stress and anxiety.”
On the other hand, Jack Gladstein, MD, a child neurologist at the University of Maryland, Baltimore, said in an interview that most of his patients suffered more headaches during the pandemic, although a small number with social anxiety thrived because they got to stay at home.
He agreed with Dr. DiSabella about the value of exercise. “At every visit we remind our youngsters with migraine to eat breakfast, exercise, get regular sleep, and drink fluids,” he said.
No study funding was reported. The study authors, Dr. Hershey, and Dr. Gladstein reported no disclosures.
, a newly released survey finds. But some actually found the pandemic era to be less stressful since they were tightly wound and could more easily control their home environments, a researcher said.
“We need to be very mindful of the connections between school and home environments – and social situations – and how they impact headache frequency,” said Marc DiSabella, DO, a pediatric neurologist at Children’s National Hospital/George Washington University, Washington. He is coauthor of a poster presented at the 50th annual meeting of the Child Neurology Society.
Dr. DiSabella and colleagues launched the survey to understand what headache patients were experiencing during the pandemic. They expected that “things were going to go really terrible in terms of headaches – or things would go great, and then things would crash when we had to reintegrate into society,” he said in an interview.
The team surveyed 113 pediatric patients who were evaluated at the hospital’s headache clinic between summer 2020 and winter 2021. Most of the patients were female (60%) and were aged 12-17 years (63%). Twenty-one percent were younger than 12 and 16% were older than 17. Chronic migraine (37%) was the most common diagnosis, followed by migraine with aura (22%), migraine without aura (19%), and new daily persistent headache (15%).
Nearly half (46%) of patients said their headaches had worsened during the pandemic. Many also reported more anxiety (55%), worsened mood (48%) and more stress (55%).
Dr. DiSabella said it’s especially notable that nearly two-thirds of those surveyed reported they were exercising less during the pandemic. Research has suggested that exercise and proper diet/sleep are crucial to improving headaches in kids, he said, and the survey findings suggest that exercise may be especially important. “Engaging in physical activity changes their pain threshold,” he said.
The researchers also reported that 60% of those surveyed said they looked at screens more than 6 hours per day. According to Dr. DiSabella, high screen use may not be worrisome from a headache perspective. “We have another study in publication that shows there’s not a clear association between frequency of screen use and headache intensity,” he said.
The survey doesn’t examine what has happened in recent weeks as schools have reopened. Anecdotally, Dr. DiSabella said some patients with migraine are feeling the stress of returning to normal routines. “They tend to be type A perfectionists and do well when they’re in control of their environment,” he said. “Now they’ve lost the control they had at home and are being put back into a stressful environment.”
Pandemic effects mixed
Commenting on the study, child neurologist Andrew D. Hershey, MD, PhD, of Cincinnati Children’s Hospital Medical Center, questioned the finding that many children suffered from more headaches during the pandemic. In his experience, “headaches were overall better when [children] were doing virtual learning,” he said in an interview. “We had fewer admissions, ED visits declined, and patients were maintaining better healthy habits. Some did express anxiety about not seeing friends, but were accommodating by doing this remotely.”
He added: “Since their return, kids are back to the same sleep deprivation issue since schools start too early, and they have more difficulty treating headaches acutely since they have to go to the nurse’s office [to do so]. They self-report a higher degree of stress and anxiety.”
On the other hand, Jack Gladstein, MD, a child neurologist at the University of Maryland, Baltimore, said in an interview that most of his patients suffered more headaches during the pandemic, although a small number with social anxiety thrived because they got to stay at home.
He agreed with Dr. DiSabella about the value of exercise. “At every visit we remind our youngsters with migraine to eat breakfast, exercise, get regular sleep, and drink fluids,” he said.
No study funding was reported. The study authors, Dr. Hershey, and Dr. Gladstein reported no disclosures.
FROM CNS 2021
Gender-affirming care ‘can save lives,’ new research shows
Transgender and nonbinary young people experienced less depression and fewer suicidal thoughts after a year of gender-affirming care with hormones or puberty blockers, according to new research.
“Given the high rates of adverse mental health comorbidities, these data provide critical evidence that expansion of gender-affirming care can save lives,” said David J. Inwards-Breland, MD, MPH, chief of adolescent and young adult medicine and codirector of the Center for Gender-Affirming Care at Rady Children’s Hospital in San Diego, during his presentation.
The findings, presented October 11 at the American Academy of Pediatrics 2021 National Conference, were not at all surprising to Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.
“The younger we can provide gender-affirming care, the less likely they’re going to have depression, and then the negative outcomes from untreated depression, which includes suicide intent or even suicide completion,” Dr. Breuner told this news organization. “It’s so obvious that we are saving lives by providing gender-affirming care.”
For their study, Dr. Inwards-Breland and his colleagues tracked depression, anxiety, and suicidality in 104 trans and nonbinary people 13 to 21 years of age who received care at the Seattle Children’s gender clinic between August 2017 and June 2018.
The study population consisted of 63 transgender male or male participants, 27 transgender female or female participants, 10 nonbinary participants, and four participants who had not defined their gender identity. Of this cohort, 62.5% were receiving mental health therapy, and 34.7% reported some substance use.
Participants completed the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) at baseline and then at 3, 6, and 12 months. The researchers defined severe depression and severe anxiety as a score of 10 or greater on either scale.
At baseline, 56.7% of the participants had moderate to severe depression, 43.3% reported thoughts of self-harm or suicidal in the previous 2 weeks, and 50.0% had moderate to severe anxiety.
After 12 months of care, participants experienced a 60% decrease in depression (adjusted odds ratio, 0.4) and a 73% decrease in suicidality (aOR, 0.27), after adjustment for temporal trends and sex assigned at birth, race/ethnicity, level of parental support, ongoing mental health therapy, substance use, and victimization, including bullying, interpersonal violence, neglect, and abuse.
Although the decline in depression and suicidality after gender-affirming treatment was not a surprise, “those drops are huge,” Dr. Inwards-Breland said in an interview.
He said he attributes the improvement to a health care system that “affirms who these young people are” and enables changes that allow their outward appearance to reflect “who they know they are inside.”
There were no significant changes in anxiety during the study period. “Anxiety, I think, is just a little harder to treat, and it takes a little longer to treat,” he explained. And a lot of factors can trigger anxiety, and those can continue during treatment.
The slow pace of changes to gender identity can have an effect on people’s moods. “Since they’re not happening quickly, these young people are still being misgendered, they’re still seeing the body that they don’t feel like they should have, and they have to go to school and go out in public. I think that continues to fuel anxiety with a lot of these young people.”
Family support is important in reducing depression and suicidal thoughts in this population. Parents will often see positive changes after their child receives gender-affirming care, which can help contribute to positive changes in parents’ attitudes, Dr. Inwards-Breland said.
Such changes reinforce “that protective factor of connectedness with family,” he noted. “Families are crucial for any health care, and if there’s that connectedness with families, we know that, clinically, patients do better.”
Balancing risks
Although there are risks associated with gender-affirming hormones and puberty blockers, the risks of not receiving treatment must also be considered.
“Our young people are killing themselves,” he said. “Our young people are developing severe eating disorders that are killing them. Our young people are increasing their substance abuse, homelessness, depression. The list just goes on.”
For trans-masculine and nonbinary masculine patients, the potential permanent changes of hormone therapy include a deeper voice, hair growth, enlargement of the clitoris, and, in some patients, the development of male pattern baldness. In trans and nonbinary feminine patients, potential long-term effects include breast development and an increased risk for fertility issues.
The consent forms required for young people who want gender-affirming hormones or puberty blockers are extensive, with every possible reversible and irreversible effect described in detail, Dr. Breuner said.
“Parents sign them because they want their child to stay alive,” she explained. “When you compare the cost of someone who has severe debilitating depression and dying by suicide with some of the risks associated with gender-affirming hormone therapy, that’s a no-brainer to me.”
This study is limited by the fact that screening tests, not diagnostic tests, were used to identify depression, anxiety, and suicidality, and the fact that the use of antidepression or antianxiety medications was not taken into account, Dr. Inwards-Breland acknowledged.
“I think future studies should look at a mental health evaluation and diagnosis by a mental health provider,” he added. And mental health, gender dysphoria, suicidality, and self-harm should be tracked over the course of treatment.
He also acknowledged the study’s selection bias. All participants sought care at a multidisciplinary gender clinic, so were likely to be privileged and to have supportive families. “There’s a good chance that if we had more trans and nonbinary youth of color, we may have different findings,” he said.
More qualitative research is needed to assess the effect of gender-affirming therapy on the mental health of these patients, Dr. Breuner said.
“Being able to finally come into who you think you are and enjoy expressing who you are in a gender-affirming way has to be positive in such a way that you’re not depressed anymore,” she added. “It has to be tragic for people who cannot stand the body they’re in and cannot talk about it to anybody or express themselves without fear of recourse, to the point that they would be so devastated that they’d want to die by suicide.”
This research was funded by the Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Development and Port Authority. Dr. Inwards-Breland and Dr. Breuner have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Transgender and nonbinary young people experienced less depression and fewer suicidal thoughts after a year of gender-affirming care with hormones or puberty blockers, according to new research.
“Given the high rates of adverse mental health comorbidities, these data provide critical evidence that expansion of gender-affirming care can save lives,” said David J. Inwards-Breland, MD, MPH, chief of adolescent and young adult medicine and codirector of the Center for Gender-Affirming Care at Rady Children’s Hospital in San Diego, during his presentation.
The findings, presented October 11 at the American Academy of Pediatrics 2021 National Conference, were not at all surprising to Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.
“The younger we can provide gender-affirming care, the less likely they’re going to have depression, and then the negative outcomes from untreated depression, which includes suicide intent or even suicide completion,” Dr. Breuner told this news organization. “It’s so obvious that we are saving lives by providing gender-affirming care.”
For their study, Dr. Inwards-Breland and his colleagues tracked depression, anxiety, and suicidality in 104 trans and nonbinary people 13 to 21 years of age who received care at the Seattle Children’s gender clinic between August 2017 and June 2018.
The study population consisted of 63 transgender male or male participants, 27 transgender female or female participants, 10 nonbinary participants, and four participants who had not defined their gender identity. Of this cohort, 62.5% were receiving mental health therapy, and 34.7% reported some substance use.
Participants completed the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) at baseline and then at 3, 6, and 12 months. The researchers defined severe depression and severe anxiety as a score of 10 or greater on either scale.
At baseline, 56.7% of the participants had moderate to severe depression, 43.3% reported thoughts of self-harm or suicidal in the previous 2 weeks, and 50.0% had moderate to severe anxiety.
After 12 months of care, participants experienced a 60% decrease in depression (adjusted odds ratio, 0.4) and a 73% decrease in suicidality (aOR, 0.27), after adjustment for temporal trends and sex assigned at birth, race/ethnicity, level of parental support, ongoing mental health therapy, substance use, and victimization, including bullying, interpersonal violence, neglect, and abuse.
Although the decline in depression and suicidality after gender-affirming treatment was not a surprise, “those drops are huge,” Dr. Inwards-Breland said in an interview.
He said he attributes the improvement to a health care system that “affirms who these young people are” and enables changes that allow their outward appearance to reflect “who they know they are inside.”
There were no significant changes in anxiety during the study period. “Anxiety, I think, is just a little harder to treat, and it takes a little longer to treat,” he explained. And a lot of factors can trigger anxiety, and those can continue during treatment.
The slow pace of changes to gender identity can have an effect on people’s moods. “Since they’re not happening quickly, these young people are still being misgendered, they’re still seeing the body that they don’t feel like they should have, and they have to go to school and go out in public. I think that continues to fuel anxiety with a lot of these young people.”
Family support is important in reducing depression and suicidal thoughts in this population. Parents will often see positive changes after their child receives gender-affirming care, which can help contribute to positive changes in parents’ attitudes, Dr. Inwards-Breland said.
Such changes reinforce “that protective factor of connectedness with family,” he noted. “Families are crucial for any health care, and if there’s that connectedness with families, we know that, clinically, patients do better.”
Balancing risks
Although there are risks associated with gender-affirming hormones and puberty blockers, the risks of not receiving treatment must also be considered.
“Our young people are killing themselves,” he said. “Our young people are developing severe eating disorders that are killing them. Our young people are increasing their substance abuse, homelessness, depression. The list just goes on.”
For trans-masculine and nonbinary masculine patients, the potential permanent changes of hormone therapy include a deeper voice, hair growth, enlargement of the clitoris, and, in some patients, the development of male pattern baldness. In trans and nonbinary feminine patients, potential long-term effects include breast development and an increased risk for fertility issues.
The consent forms required for young people who want gender-affirming hormones or puberty blockers are extensive, with every possible reversible and irreversible effect described in detail, Dr. Breuner said.
“Parents sign them because they want their child to stay alive,” she explained. “When you compare the cost of someone who has severe debilitating depression and dying by suicide with some of the risks associated with gender-affirming hormone therapy, that’s a no-brainer to me.”
This study is limited by the fact that screening tests, not diagnostic tests, were used to identify depression, anxiety, and suicidality, and the fact that the use of antidepression or antianxiety medications was not taken into account, Dr. Inwards-Breland acknowledged.
“I think future studies should look at a mental health evaluation and diagnosis by a mental health provider,” he added. And mental health, gender dysphoria, suicidality, and self-harm should be tracked over the course of treatment.
He also acknowledged the study’s selection bias. All participants sought care at a multidisciplinary gender clinic, so were likely to be privileged and to have supportive families. “There’s a good chance that if we had more trans and nonbinary youth of color, we may have different findings,” he said.
More qualitative research is needed to assess the effect of gender-affirming therapy on the mental health of these patients, Dr. Breuner said.
“Being able to finally come into who you think you are and enjoy expressing who you are in a gender-affirming way has to be positive in such a way that you’re not depressed anymore,” she added. “It has to be tragic for people who cannot stand the body they’re in and cannot talk about it to anybody or express themselves without fear of recourse, to the point that they would be so devastated that they’d want to die by suicide.”
This research was funded by the Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Development and Port Authority. Dr. Inwards-Breland and Dr. Breuner have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Transgender and nonbinary young people experienced less depression and fewer suicidal thoughts after a year of gender-affirming care with hormones or puberty blockers, according to new research.
“Given the high rates of adverse mental health comorbidities, these data provide critical evidence that expansion of gender-affirming care can save lives,” said David J. Inwards-Breland, MD, MPH, chief of adolescent and young adult medicine and codirector of the Center for Gender-Affirming Care at Rady Children’s Hospital in San Diego, during his presentation.
The findings, presented October 11 at the American Academy of Pediatrics 2021 National Conference, were not at all surprising to Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.
“The younger we can provide gender-affirming care, the less likely they’re going to have depression, and then the negative outcomes from untreated depression, which includes suicide intent or even suicide completion,” Dr. Breuner told this news organization. “It’s so obvious that we are saving lives by providing gender-affirming care.”
For their study, Dr. Inwards-Breland and his colleagues tracked depression, anxiety, and suicidality in 104 trans and nonbinary people 13 to 21 years of age who received care at the Seattle Children’s gender clinic between August 2017 and June 2018.
The study population consisted of 63 transgender male or male participants, 27 transgender female or female participants, 10 nonbinary participants, and four participants who had not defined their gender identity. Of this cohort, 62.5% were receiving mental health therapy, and 34.7% reported some substance use.
Participants completed the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) at baseline and then at 3, 6, and 12 months. The researchers defined severe depression and severe anxiety as a score of 10 or greater on either scale.
At baseline, 56.7% of the participants had moderate to severe depression, 43.3% reported thoughts of self-harm or suicidal in the previous 2 weeks, and 50.0% had moderate to severe anxiety.
After 12 months of care, participants experienced a 60% decrease in depression (adjusted odds ratio, 0.4) and a 73% decrease in suicidality (aOR, 0.27), after adjustment for temporal trends and sex assigned at birth, race/ethnicity, level of parental support, ongoing mental health therapy, substance use, and victimization, including bullying, interpersonal violence, neglect, and abuse.
Although the decline in depression and suicidality after gender-affirming treatment was not a surprise, “those drops are huge,” Dr. Inwards-Breland said in an interview.
He said he attributes the improvement to a health care system that “affirms who these young people are” and enables changes that allow their outward appearance to reflect “who they know they are inside.”
There were no significant changes in anxiety during the study period. “Anxiety, I think, is just a little harder to treat, and it takes a little longer to treat,” he explained. And a lot of factors can trigger anxiety, and those can continue during treatment.
The slow pace of changes to gender identity can have an effect on people’s moods. “Since they’re not happening quickly, these young people are still being misgendered, they’re still seeing the body that they don’t feel like they should have, and they have to go to school and go out in public. I think that continues to fuel anxiety with a lot of these young people.”
Family support is important in reducing depression and suicidal thoughts in this population. Parents will often see positive changes after their child receives gender-affirming care, which can help contribute to positive changes in parents’ attitudes, Dr. Inwards-Breland said.
Such changes reinforce “that protective factor of connectedness with family,” he noted. “Families are crucial for any health care, and if there’s that connectedness with families, we know that, clinically, patients do better.”
Balancing risks
Although there are risks associated with gender-affirming hormones and puberty blockers, the risks of not receiving treatment must also be considered.
“Our young people are killing themselves,” he said. “Our young people are developing severe eating disorders that are killing them. Our young people are increasing their substance abuse, homelessness, depression. The list just goes on.”
For trans-masculine and nonbinary masculine patients, the potential permanent changes of hormone therapy include a deeper voice, hair growth, enlargement of the clitoris, and, in some patients, the development of male pattern baldness. In trans and nonbinary feminine patients, potential long-term effects include breast development and an increased risk for fertility issues.
The consent forms required for young people who want gender-affirming hormones or puberty blockers are extensive, with every possible reversible and irreversible effect described in detail, Dr. Breuner said.
“Parents sign them because they want their child to stay alive,” she explained. “When you compare the cost of someone who has severe debilitating depression and dying by suicide with some of the risks associated with gender-affirming hormone therapy, that’s a no-brainer to me.”
This study is limited by the fact that screening tests, not diagnostic tests, were used to identify depression, anxiety, and suicidality, and the fact that the use of antidepression or antianxiety medications was not taken into account, Dr. Inwards-Breland acknowledged.
“I think future studies should look at a mental health evaluation and diagnosis by a mental health provider,” he added. And mental health, gender dysphoria, suicidality, and self-harm should be tracked over the course of treatment.
He also acknowledged the study’s selection bias. All participants sought care at a multidisciplinary gender clinic, so were likely to be privileged and to have supportive families. “There’s a good chance that if we had more trans and nonbinary youth of color, we may have different findings,” he said.
More qualitative research is needed to assess the effect of gender-affirming therapy on the mental health of these patients, Dr. Breuner said.
“Being able to finally come into who you think you are and enjoy expressing who you are in a gender-affirming way has to be positive in such a way that you’re not depressed anymore,” she added. “It has to be tragic for people who cannot stand the body they’re in and cannot talk about it to anybody or express themselves without fear of recourse, to the point that they would be so devastated that they’d want to die by suicide.”
This research was funded by the Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Development and Port Authority. Dr. Inwards-Breland and Dr. Breuner have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Radiofrequency ablation gains favor for thyroid nodules in U.S.
And in one case, a hospital has taken the unique step of forming a multidisciplinary thyroid nodule RFA tumor board, which helps in the often tricky decision-making process that is involved.
“Our multidisciplinary RFA tumor board has been invaluable in this process, and it is the only one of its kind in the nation that I’m aware of,” James Lim, MD, of the Division of Surgical Oncology, Thyroid, and Parathyroid Center at Oregon Health Sciences University (OHSU), told this news organization.
Dr. Lim reports receiving referrals from “all avenues, some from thyroid specialists and others from nonthyroid specialists such as primary care practitioners or patient self-referrals.”
“Because of this, our centralized process of multidisciplinary review ensures that each patient is evaluated thoroughly through each thyroid specialists’ lens to optimize patient outcomes,” noted Dr. Lim, an assistant professor of endocrine surgery.
The RFA tumor board consists of experts in all specialties involved in thyroid nodule assessment and treatment, including surgeons, interventional radiologists, and endocrinologists.
Just because you can, doesn’t mean you should
However, there should be some caution that although there is enthusiasm regarding this noninvasive alternative to surgery, there is another option, that of mere observation, which is appropriate in many cases of thyroid nodules and should not be overlooked.
“For a number of reasons, the key to keep in mind is that, just because we can do something doesn’t mean we should,” Michael Singer, MD, director of the Division of Thyroid & Parathyroid Surgery, Department of Otolaryngology – Head and Neck Surgery, at the Henry Ford Health System, Detroit, said in an interview.
While emphasizing that he believes RFA to be a promising technology that will likely benefit patients in the future, Dr. Singer voiced concern about the approach becoming an easy choice – particularly if profit is to be had – when observation is a clear alternative. “If RFA becomes seen as an opportunity to create revenue, potential conflicts of interest may arise,” he said.
“As it is not a major procedure with a dramatic risk profile, my concern is that some clinicians [could] adopt the attitude of ‘Why not do it?’ even when the indication is minimal or nonexistent,” he added.
Dr. Lim said he agrees that “any new medical technology requires thoughtful evaluation and appropriate patient selection in order to ensure optimal patient outcomes.”
That’s where the tumor board has been especially beneficial.
“We have found great benefit in reviewing potential RFA cases in a multidisciplinary fashion within our tumor board and would recommend other institutions to consider it,” he noted. In the absence of a tumor board, “at a minimum, a thyroid specialist should be involved in the evaluation of a potential thyroid RFA patient prior to ablation treatment,” he advised.
Tumor board was able to identify a small subset of patients for surgery
In his research presented at the 90th Annual Meeting of the American Thyroid Association (ATA), Dr. Lim and colleagues evaluated the tumor board’s efficacy in altering diagnosis and treatment plans in a retrospective review of cases presented to the board for RFA consideration since its inception in July 2020 through June 2021.
Over the study period, 65 patients with biopsy-proven benign thyroid nodules were newly referred for RFA, with 58 referred for mass effect symptoms and seven for autonomous function.
After the multidisciplinary review, about half of the cases, 37 (56.9%), were approved for RFA.
Of the remainder, 22 (33.8%) were determined to need additional studies, just two (3.0%) were recommended for surgery, and four (6.2%) were recommended to not receive any intervention.
Of the 22 cases recommended for additional studies, 15 were subsequently recommended for RFA and four were recommended to receive surgery due to suspicious clinical findings.
Of those that underwent surgery, two showed thyroid cancer on final pathology.
Among the nodules recommended to RFA, the average nodule volume was 15.1 mL, whereas the average volume for those recommended for surgery was 40.9 mL (P = .08).
No significant complications occurred among patients that underwent RFA or those who had surgery.
“The tumor board’s multidisciplinary review was able to identify high-risk features in some patients with benign biopsies. This led to a change in recommendation from RFA to surgery for possible malignancy in a small subset of patients,” Dr. Lim noted.
In a separate analysis, Dr. Lim and colleagues reported that, among patients treated with RFA (with a mean baseline nodule volume of 11.9 mL), mean nodule volume was 6.4 mL after 1 month, 4.5 mL after 3 months, and 3.8 mL at 6 months, which were all significantly reduced versus baseline (P < .001). Similar improvements were also reported in symptom and cosmetic scores at each timepoint (all P < .001).
There were no cases of postprocedural hypothyroidism or symptomatic thyrotoxicosis.
Underlining that patients can expect noticeable improvement in symptom scores by their 30-day visit, Dr. Lim noted that patients should be warned of some early swelling.
“It is important to inform patients that they may have swelling of their treated nodule immediately after the procedure, but this should subside within a few days,” he said.
Outpatient RFA safe and efficacious
In a separate study also presented at the meeting, three practitioners described their experiences with RFA in their outpatient thyroid practices in San Antonio; Santa Monica, California; and Gettysburg, Pennsylvania.
Overall, there were 68 cases involving benign, class II thyroid nodules, and the authors reported average procedure times of under an hour, with actual RFA time varying from 7 to 22 minutes.
Of note, for nodules larger than 4.5 cm, two procedures were necessary to achieve desired results.
Excluding the larger nodules requiring more than one procedure, there was an average decrease in nodule size of 48% at 1 month and a decrease of 82% after 3 months in more than 80% of cases.
None of the cases required surgery. There were no major complications, and all patients had preserved baseline thyroid function.
“This preliminary study of 68 patients shows how thyroid RFA is safe and efficacious when performed in an endocrine outpatient office practice,” Kathleen Hands, MD, of the Thyroid Center of South Texas, and coauthors concluded.
Insurance coverage an issue in U.S.
Among much larger studies demonstrating the safety and efficacy of RFA for benign nodules, a study of 450 Chinese patients published in January showed RFA to be superior to conventional thyroidectomy in terms of patient satisfaction, postoperative quality of life, and shorter hospital stay, although the caveat was it took longer to achieve nodule volume reduction.
But if RFA use is to become more widespread in the United States, a key obstacle is that insurance companies generally do not cover the procedure. Although patients in Dr. Lim’s analyses did have coverage, it didn’t come easily, he said.
“Thankfully, all of our patients have been approved by insurance, and no one has had to pay by themselves, but this has sometimes required multiple appeals to the insurance company,” Dr. Lim said.
“The American Association of Endocrine Surgeons and Society of Interventional Radiology are both working towards getting this valuable treatment more readily accepted by more insurance companies,” he said.
Dr. Lim and Dr. Singer have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
And in one case, a hospital has taken the unique step of forming a multidisciplinary thyroid nodule RFA tumor board, which helps in the often tricky decision-making process that is involved.
“Our multidisciplinary RFA tumor board has been invaluable in this process, and it is the only one of its kind in the nation that I’m aware of,” James Lim, MD, of the Division of Surgical Oncology, Thyroid, and Parathyroid Center at Oregon Health Sciences University (OHSU), told this news organization.
Dr. Lim reports receiving referrals from “all avenues, some from thyroid specialists and others from nonthyroid specialists such as primary care practitioners or patient self-referrals.”
“Because of this, our centralized process of multidisciplinary review ensures that each patient is evaluated thoroughly through each thyroid specialists’ lens to optimize patient outcomes,” noted Dr. Lim, an assistant professor of endocrine surgery.
The RFA tumor board consists of experts in all specialties involved in thyroid nodule assessment and treatment, including surgeons, interventional radiologists, and endocrinologists.
Just because you can, doesn’t mean you should
However, there should be some caution that although there is enthusiasm regarding this noninvasive alternative to surgery, there is another option, that of mere observation, which is appropriate in many cases of thyroid nodules and should not be overlooked.
“For a number of reasons, the key to keep in mind is that, just because we can do something doesn’t mean we should,” Michael Singer, MD, director of the Division of Thyroid & Parathyroid Surgery, Department of Otolaryngology – Head and Neck Surgery, at the Henry Ford Health System, Detroit, said in an interview.
While emphasizing that he believes RFA to be a promising technology that will likely benefit patients in the future, Dr. Singer voiced concern about the approach becoming an easy choice – particularly if profit is to be had – when observation is a clear alternative. “If RFA becomes seen as an opportunity to create revenue, potential conflicts of interest may arise,” he said.
“As it is not a major procedure with a dramatic risk profile, my concern is that some clinicians [could] adopt the attitude of ‘Why not do it?’ even when the indication is minimal or nonexistent,” he added.
Dr. Lim said he agrees that “any new medical technology requires thoughtful evaluation and appropriate patient selection in order to ensure optimal patient outcomes.”
That’s where the tumor board has been especially beneficial.
“We have found great benefit in reviewing potential RFA cases in a multidisciplinary fashion within our tumor board and would recommend other institutions to consider it,” he noted. In the absence of a tumor board, “at a minimum, a thyroid specialist should be involved in the evaluation of a potential thyroid RFA patient prior to ablation treatment,” he advised.
Tumor board was able to identify a small subset of patients for surgery
In his research presented at the 90th Annual Meeting of the American Thyroid Association (ATA), Dr. Lim and colleagues evaluated the tumor board’s efficacy in altering diagnosis and treatment plans in a retrospective review of cases presented to the board for RFA consideration since its inception in July 2020 through June 2021.
Over the study period, 65 patients with biopsy-proven benign thyroid nodules were newly referred for RFA, with 58 referred for mass effect symptoms and seven for autonomous function.
After the multidisciplinary review, about half of the cases, 37 (56.9%), were approved for RFA.
Of the remainder, 22 (33.8%) were determined to need additional studies, just two (3.0%) were recommended for surgery, and four (6.2%) were recommended to not receive any intervention.
Of the 22 cases recommended for additional studies, 15 were subsequently recommended for RFA and four were recommended to receive surgery due to suspicious clinical findings.
Of those that underwent surgery, two showed thyroid cancer on final pathology.
Among the nodules recommended to RFA, the average nodule volume was 15.1 mL, whereas the average volume for those recommended for surgery was 40.9 mL (P = .08).
No significant complications occurred among patients that underwent RFA or those who had surgery.
“The tumor board’s multidisciplinary review was able to identify high-risk features in some patients with benign biopsies. This led to a change in recommendation from RFA to surgery for possible malignancy in a small subset of patients,” Dr. Lim noted.
In a separate analysis, Dr. Lim and colleagues reported that, among patients treated with RFA (with a mean baseline nodule volume of 11.9 mL), mean nodule volume was 6.4 mL after 1 month, 4.5 mL after 3 months, and 3.8 mL at 6 months, which were all significantly reduced versus baseline (P < .001). Similar improvements were also reported in symptom and cosmetic scores at each timepoint (all P < .001).
There were no cases of postprocedural hypothyroidism or symptomatic thyrotoxicosis.
Underlining that patients can expect noticeable improvement in symptom scores by their 30-day visit, Dr. Lim noted that patients should be warned of some early swelling.
“It is important to inform patients that they may have swelling of their treated nodule immediately after the procedure, but this should subside within a few days,” he said.
Outpatient RFA safe and efficacious
In a separate study also presented at the meeting, three practitioners described their experiences with RFA in their outpatient thyroid practices in San Antonio; Santa Monica, California; and Gettysburg, Pennsylvania.
Overall, there were 68 cases involving benign, class II thyroid nodules, and the authors reported average procedure times of under an hour, with actual RFA time varying from 7 to 22 minutes.
Of note, for nodules larger than 4.5 cm, two procedures were necessary to achieve desired results.
Excluding the larger nodules requiring more than one procedure, there was an average decrease in nodule size of 48% at 1 month and a decrease of 82% after 3 months in more than 80% of cases.
None of the cases required surgery. There were no major complications, and all patients had preserved baseline thyroid function.
“This preliminary study of 68 patients shows how thyroid RFA is safe and efficacious when performed in an endocrine outpatient office practice,” Kathleen Hands, MD, of the Thyroid Center of South Texas, and coauthors concluded.
Insurance coverage an issue in U.S.
Among much larger studies demonstrating the safety and efficacy of RFA for benign nodules, a study of 450 Chinese patients published in January showed RFA to be superior to conventional thyroidectomy in terms of patient satisfaction, postoperative quality of life, and shorter hospital stay, although the caveat was it took longer to achieve nodule volume reduction.
But if RFA use is to become more widespread in the United States, a key obstacle is that insurance companies generally do not cover the procedure. Although patients in Dr. Lim’s analyses did have coverage, it didn’t come easily, he said.
“Thankfully, all of our patients have been approved by insurance, and no one has had to pay by themselves, but this has sometimes required multiple appeals to the insurance company,” Dr. Lim said.
“The American Association of Endocrine Surgeons and Society of Interventional Radiology are both working towards getting this valuable treatment more readily accepted by more insurance companies,” he said.
Dr. Lim and Dr. Singer have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
And in one case, a hospital has taken the unique step of forming a multidisciplinary thyroid nodule RFA tumor board, which helps in the often tricky decision-making process that is involved.
“Our multidisciplinary RFA tumor board has been invaluable in this process, and it is the only one of its kind in the nation that I’m aware of,” James Lim, MD, of the Division of Surgical Oncology, Thyroid, and Parathyroid Center at Oregon Health Sciences University (OHSU), told this news organization.
Dr. Lim reports receiving referrals from “all avenues, some from thyroid specialists and others from nonthyroid specialists such as primary care practitioners or patient self-referrals.”
“Because of this, our centralized process of multidisciplinary review ensures that each patient is evaluated thoroughly through each thyroid specialists’ lens to optimize patient outcomes,” noted Dr. Lim, an assistant professor of endocrine surgery.
The RFA tumor board consists of experts in all specialties involved in thyroid nodule assessment and treatment, including surgeons, interventional radiologists, and endocrinologists.
Just because you can, doesn’t mean you should
However, there should be some caution that although there is enthusiasm regarding this noninvasive alternative to surgery, there is another option, that of mere observation, which is appropriate in many cases of thyroid nodules and should not be overlooked.
“For a number of reasons, the key to keep in mind is that, just because we can do something doesn’t mean we should,” Michael Singer, MD, director of the Division of Thyroid & Parathyroid Surgery, Department of Otolaryngology – Head and Neck Surgery, at the Henry Ford Health System, Detroit, said in an interview.
While emphasizing that he believes RFA to be a promising technology that will likely benefit patients in the future, Dr. Singer voiced concern about the approach becoming an easy choice – particularly if profit is to be had – when observation is a clear alternative. “If RFA becomes seen as an opportunity to create revenue, potential conflicts of interest may arise,” he said.
“As it is not a major procedure with a dramatic risk profile, my concern is that some clinicians [could] adopt the attitude of ‘Why not do it?’ even when the indication is minimal or nonexistent,” he added.
Dr. Lim said he agrees that “any new medical technology requires thoughtful evaluation and appropriate patient selection in order to ensure optimal patient outcomes.”
That’s where the tumor board has been especially beneficial.
“We have found great benefit in reviewing potential RFA cases in a multidisciplinary fashion within our tumor board and would recommend other institutions to consider it,” he noted. In the absence of a tumor board, “at a minimum, a thyroid specialist should be involved in the evaluation of a potential thyroid RFA patient prior to ablation treatment,” he advised.
Tumor board was able to identify a small subset of patients for surgery
In his research presented at the 90th Annual Meeting of the American Thyroid Association (ATA), Dr. Lim and colleagues evaluated the tumor board’s efficacy in altering diagnosis and treatment plans in a retrospective review of cases presented to the board for RFA consideration since its inception in July 2020 through June 2021.
Over the study period, 65 patients with biopsy-proven benign thyroid nodules were newly referred for RFA, with 58 referred for mass effect symptoms and seven for autonomous function.
After the multidisciplinary review, about half of the cases, 37 (56.9%), were approved for RFA.
Of the remainder, 22 (33.8%) were determined to need additional studies, just two (3.0%) were recommended for surgery, and four (6.2%) were recommended to not receive any intervention.
Of the 22 cases recommended for additional studies, 15 were subsequently recommended for RFA and four were recommended to receive surgery due to suspicious clinical findings.
Of those that underwent surgery, two showed thyroid cancer on final pathology.
Among the nodules recommended to RFA, the average nodule volume was 15.1 mL, whereas the average volume for those recommended for surgery was 40.9 mL (P = .08).
No significant complications occurred among patients that underwent RFA or those who had surgery.
“The tumor board’s multidisciplinary review was able to identify high-risk features in some patients with benign biopsies. This led to a change in recommendation from RFA to surgery for possible malignancy in a small subset of patients,” Dr. Lim noted.
In a separate analysis, Dr. Lim and colleagues reported that, among patients treated with RFA (with a mean baseline nodule volume of 11.9 mL), mean nodule volume was 6.4 mL after 1 month, 4.5 mL after 3 months, and 3.8 mL at 6 months, which were all significantly reduced versus baseline (P < .001). Similar improvements were also reported in symptom and cosmetic scores at each timepoint (all P < .001).
There were no cases of postprocedural hypothyroidism or symptomatic thyrotoxicosis.
Underlining that patients can expect noticeable improvement in symptom scores by their 30-day visit, Dr. Lim noted that patients should be warned of some early swelling.
“It is important to inform patients that they may have swelling of their treated nodule immediately after the procedure, but this should subside within a few days,” he said.
Outpatient RFA safe and efficacious
In a separate study also presented at the meeting, three practitioners described their experiences with RFA in their outpatient thyroid practices in San Antonio; Santa Monica, California; and Gettysburg, Pennsylvania.
Overall, there were 68 cases involving benign, class II thyroid nodules, and the authors reported average procedure times of under an hour, with actual RFA time varying from 7 to 22 minutes.
Of note, for nodules larger than 4.5 cm, two procedures were necessary to achieve desired results.
Excluding the larger nodules requiring more than one procedure, there was an average decrease in nodule size of 48% at 1 month and a decrease of 82% after 3 months in more than 80% of cases.
None of the cases required surgery. There were no major complications, and all patients had preserved baseline thyroid function.
“This preliminary study of 68 patients shows how thyroid RFA is safe and efficacious when performed in an endocrine outpatient office practice,” Kathleen Hands, MD, of the Thyroid Center of South Texas, and coauthors concluded.
Insurance coverage an issue in U.S.
Among much larger studies demonstrating the safety and efficacy of RFA for benign nodules, a study of 450 Chinese patients published in January showed RFA to be superior to conventional thyroidectomy in terms of patient satisfaction, postoperative quality of life, and shorter hospital stay, although the caveat was it took longer to achieve nodule volume reduction.
But if RFA use is to become more widespread in the United States, a key obstacle is that insurance companies generally do not cover the procedure. Although patients in Dr. Lim’s analyses did have coverage, it didn’t come easily, he said.
“Thankfully, all of our patients have been approved by insurance, and no one has had to pay by themselves, but this has sometimes required multiple appeals to the insurance company,” Dr. Lim said.
“The American Association of Endocrine Surgeons and Society of Interventional Radiology are both working towards getting this valuable treatment more readily accepted by more insurance companies,” he said.
Dr. Lim and Dr. Singer have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘Impressive’ results for novel antidepressant, so why the FDA delay?
A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.
In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
The study
The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.
Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m2.
The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.
Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.
By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.
The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.
Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.
These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.
Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.
The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.
The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.
and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.
Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.
FDA delay
Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.
As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”
With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.
Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”
“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
‘Impressive’ remission rate
Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”
However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.
He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”
The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.
A version of this article first appeared on Medscape.com.
A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.
In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
The study
The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.
Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m2.
The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.
Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.
By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.
The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.
Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.
These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.
Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.
The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.
The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.
and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.
Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.
FDA delay
Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.
As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”
With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.
Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”
“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
‘Impressive’ remission rate
Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”
However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.
He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”
The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.
A version of this article first appeared on Medscape.com.
A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.
In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
The study
The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.
Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m2.
The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.
Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.
By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.
The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.
Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.
These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.
Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.
The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.
The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.
and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.
Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.
FDA delay
Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.
As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”
With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.
Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”
“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
‘Impressive’ remission rate
Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”
However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.
He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”
The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.
A version of this article first appeared on Medscape.com.
FROM ECNP 2021