User login
Rapid response to PTSD therapy may predict long-term improvement
Patients who experience a rapid response to cognitive processing therapy (CPT) for posttraumatic stress disorder have a greater likelihood of sustained improvement, new research suggests.
A study of 136 veterans with PTSD showed that those who responded quickly to a 3-week CPT program were significantly more likely to report lower symptom scores 3 months post treatment, compared with those participants who responded more slowly.
The results add to previous evidence that intensified, short-term treatment programs can accomplish long-term benefits, noted the investigators, led by Jenna Bagley, Rush University Medical Center, Chicago.
“These findings show promise for the success of condensed evidence-based, trauma-focused interventions,” they added.
Ms. Bagley was scheduled to present the study in March at the Anxiety and Depression Association of America (ADAA) Conference 2020. That conference was canceled because of the coronavirus pandemic.
Reducing high dropout rates
PTSD treatments such as CPT and prolonged exposure have been shown to have high efficacy, but they also have been shown to have a nearly 40% dropout rate, the researchers note.
This problem has prompted a focus on shorter-term interventions that can deliver intensified treatment before participants drop out. However, evidence has been lacking as to the sustainability of symptom improvements that occur in a short period.
The researchers evaluated data on 136 veterans (66% men; mean age, 41 years) with PTSD who completed a non–Veterans Affairs, 3-week CPT-based intensive treatment program. Follow-up assessments were carried out at 3 months.
Symptom reduction rates represented the number of days from intake in the program to the first day a reduction was reported of at least 15 points on the PTSD Checklist for DSM-5 (PCL-5), which was indicative of a clinically meaningful improvement.
Results showed representing greater ongoing symptoms (P = .04).
The amount of time to reach the 15-point reduction also predicted symptom reductions at the 3-month follow-up, even when controlling for the total change in PCL-5 score during the program (P = .03) and when controlling for type of trauma, such as combat or military sexual trauma.
Another puzzle piece?
Commenting on the study, David C. Rozek, PhD, assistant professor at the University of Central Florida, Orlando, said the findings are encouraging, particularly in terms of improvements seen with shorter treatment programs.
“Sudden gains are important to look at in all treatments,” said Dr. Rozek, who was not involved with the research.
“Seeing that these sudden gains occur in intensive treatment and predict long-term outcome provides another piece of the puzzle and provides additional support to intensive treatments,” he added.
Dr. Rozek noted that he has also observed this with patients. However, they, along with mental health practitioners, often question whether short-term improvements will last.
“There is some concern that a rapid drop in a patient’s symptoms could be an increased risk for a rebound,” he said.
“However, that is when the skills learned in therapy can kick in and provide [patients] tools to use in their everyday life and to help continue recovering,” he added.
Dr. Rozek was scheduled to report results from a pilot study on his own experience at the canceled ADAA meeting. The study was about an even shorter, 7-day intensive CPT program (CPT-7) conducted through the National Center for Veterans Studies.
The program involved one daily individual CPT-7 session with a mental health provider in the morning followed by optional group recreational activities in the afternoon. Twelve military personnel in two cohorts with either PTSD or subthreshold PTSD, defined as having all but one symptom cluster present, were included in the study.
Keep patients engaged
Preliminary results showed reductions in PCL-5 scores from pre- to posttreatment of approximately 40% (P < .001).
“Just over 50% of patients left [the program] with symptoms below probable PTSD diagnosis on a self-report measure,” Dr. Rozek said.
Importantly, none of the participants dropped out of the treatment, but Dr. Rozek said that this was not necessarily surprising because of the nature of the program.
“These patients are brought in as a cohort and form some bonds, as they all have experienced traumatic events, although often [they have had] very different traumas,” he said.
“We’ve found that by doing daily treatment, it is more accessible and removes barriers, as it is often easier to take a week or a few weeks off at a time and participate in treatment than the logistics of weekly treatment,” he added.
Dr. Rozek said he suspects two key factors may predict treatment response in such programs – cognitive flexibility and emotion regulation.
“Patients who come into treatment and are extremely rigid in their thinking and are unable to manage their emotions may be slower to respond to treatment,” he noted.
“That being said, there are a variety of treatments that target these factors in different ways. Now we need to do the work to determine which treatments work for whom.”
The findings on longer-term durability of rapid improvement bode well for the program. “Although the work in treatment is hard, they patients really start to see the gains quickly, within a week or weeks instead of months,” Dr. Rozek said.
“This is rewarding in itself, and I would say is a strong factor for keeping patients engaged,” he concluded.
Dr. Rozek has received research funding from the National Institutes of Health, the Department of Defense, the Bob Woodruff Foundation, and the Boeing Corporation.
A version of this article originally appeared on Medscape.com.
Patients who experience a rapid response to cognitive processing therapy (CPT) for posttraumatic stress disorder have a greater likelihood of sustained improvement, new research suggests.
A study of 136 veterans with PTSD showed that those who responded quickly to a 3-week CPT program were significantly more likely to report lower symptom scores 3 months post treatment, compared with those participants who responded more slowly.
The results add to previous evidence that intensified, short-term treatment programs can accomplish long-term benefits, noted the investigators, led by Jenna Bagley, Rush University Medical Center, Chicago.
“These findings show promise for the success of condensed evidence-based, trauma-focused interventions,” they added.
Ms. Bagley was scheduled to present the study in March at the Anxiety and Depression Association of America (ADAA) Conference 2020. That conference was canceled because of the coronavirus pandemic.
Reducing high dropout rates
PTSD treatments such as CPT and prolonged exposure have been shown to have high efficacy, but they also have been shown to have a nearly 40% dropout rate, the researchers note.
This problem has prompted a focus on shorter-term interventions that can deliver intensified treatment before participants drop out. However, evidence has been lacking as to the sustainability of symptom improvements that occur in a short period.
The researchers evaluated data on 136 veterans (66% men; mean age, 41 years) with PTSD who completed a non–Veterans Affairs, 3-week CPT-based intensive treatment program. Follow-up assessments were carried out at 3 months.
Symptom reduction rates represented the number of days from intake in the program to the first day a reduction was reported of at least 15 points on the PTSD Checklist for DSM-5 (PCL-5), which was indicative of a clinically meaningful improvement.
Results showed representing greater ongoing symptoms (P = .04).
The amount of time to reach the 15-point reduction also predicted symptom reductions at the 3-month follow-up, even when controlling for the total change in PCL-5 score during the program (P = .03) and when controlling for type of trauma, such as combat or military sexual trauma.
Another puzzle piece?
Commenting on the study, David C. Rozek, PhD, assistant professor at the University of Central Florida, Orlando, said the findings are encouraging, particularly in terms of improvements seen with shorter treatment programs.
“Sudden gains are important to look at in all treatments,” said Dr. Rozek, who was not involved with the research.
“Seeing that these sudden gains occur in intensive treatment and predict long-term outcome provides another piece of the puzzle and provides additional support to intensive treatments,” he added.
Dr. Rozek noted that he has also observed this with patients. However, they, along with mental health practitioners, often question whether short-term improvements will last.
“There is some concern that a rapid drop in a patient’s symptoms could be an increased risk for a rebound,” he said.
“However, that is when the skills learned in therapy can kick in and provide [patients] tools to use in their everyday life and to help continue recovering,” he added.
Dr. Rozek was scheduled to report results from a pilot study on his own experience at the canceled ADAA meeting. The study was about an even shorter, 7-day intensive CPT program (CPT-7) conducted through the National Center for Veterans Studies.
The program involved one daily individual CPT-7 session with a mental health provider in the morning followed by optional group recreational activities in the afternoon. Twelve military personnel in two cohorts with either PTSD or subthreshold PTSD, defined as having all but one symptom cluster present, were included in the study.
Keep patients engaged
Preliminary results showed reductions in PCL-5 scores from pre- to posttreatment of approximately 40% (P < .001).
“Just over 50% of patients left [the program] with symptoms below probable PTSD diagnosis on a self-report measure,” Dr. Rozek said.
Importantly, none of the participants dropped out of the treatment, but Dr. Rozek said that this was not necessarily surprising because of the nature of the program.
“These patients are brought in as a cohort and form some bonds, as they all have experienced traumatic events, although often [they have had] very different traumas,” he said.
“We’ve found that by doing daily treatment, it is more accessible and removes barriers, as it is often easier to take a week or a few weeks off at a time and participate in treatment than the logistics of weekly treatment,” he added.
Dr. Rozek said he suspects two key factors may predict treatment response in such programs – cognitive flexibility and emotion regulation.
“Patients who come into treatment and are extremely rigid in their thinking and are unable to manage their emotions may be slower to respond to treatment,” he noted.
“That being said, there are a variety of treatments that target these factors in different ways. Now we need to do the work to determine which treatments work for whom.”
The findings on longer-term durability of rapid improvement bode well for the program. “Although the work in treatment is hard, they patients really start to see the gains quickly, within a week or weeks instead of months,” Dr. Rozek said.
“This is rewarding in itself, and I would say is a strong factor for keeping patients engaged,” he concluded.
Dr. Rozek has received research funding from the National Institutes of Health, the Department of Defense, the Bob Woodruff Foundation, and the Boeing Corporation.
A version of this article originally appeared on Medscape.com.
Patients who experience a rapid response to cognitive processing therapy (CPT) for posttraumatic stress disorder have a greater likelihood of sustained improvement, new research suggests.
A study of 136 veterans with PTSD showed that those who responded quickly to a 3-week CPT program were significantly more likely to report lower symptom scores 3 months post treatment, compared with those participants who responded more slowly.
The results add to previous evidence that intensified, short-term treatment programs can accomplish long-term benefits, noted the investigators, led by Jenna Bagley, Rush University Medical Center, Chicago.
“These findings show promise for the success of condensed evidence-based, trauma-focused interventions,” they added.
Ms. Bagley was scheduled to present the study in March at the Anxiety and Depression Association of America (ADAA) Conference 2020. That conference was canceled because of the coronavirus pandemic.
Reducing high dropout rates
PTSD treatments such as CPT and prolonged exposure have been shown to have high efficacy, but they also have been shown to have a nearly 40% dropout rate, the researchers note.
This problem has prompted a focus on shorter-term interventions that can deliver intensified treatment before participants drop out. However, evidence has been lacking as to the sustainability of symptom improvements that occur in a short period.
The researchers evaluated data on 136 veterans (66% men; mean age, 41 years) with PTSD who completed a non–Veterans Affairs, 3-week CPT-based intensive treatment program. Follow-up assessments were carried out at 3 months.
Symptom reduction rates represented the number of days from intake in the program to the first day a reduction was reported of at least 15 points on the PTSD Checklist for DSM-5 (PCL-5), which was indicative of a clinically meaningful improvement.
Results showed representing greater ongoing symptoms (P = .04).
The amount of time to reach the 15-point reduction also predicted symptom reductions at the 3-month follow-up, even when controlling for the total change in PCL-5 score during the program (P = .03) and when controlling for type of trauma, such as combat or military sexual trauma.
Another puzzle piece?
Commenting on the study, David C. Rozek, PhD, assistant professor at the University of Central Florida, Orlando, said the findings are encouraging, particularly in terms of improvements seen with shorter treatment programs.
“Sudden gains are important to look at in all treatments,” said Dr. Rozek, who was not involved with the research.
“Seeing that these sudden gains occur in intensive treatment and predict long-term outcome provides another piece of the puzzle and provides additional support to intensive treatments,” he added.
Dr. Rozek noted that he has also observed this with patients. However, they, along with mental health practitioners, often question whether short-term improvements will last.
“There is some concern that a rapid drop in a patient’s symptoms could be an increased risk for a rebound,” he said.
“However, that is when the skills learned in therapy can kick in and provide [patients] tools to use in their everyday life and to help continue recovering,” he added.
Dr. Rozek was scheduled to report results from a pilot study on his own experience at the canceled ADAA meeting. The study was about an even shorter, 7-day intensive CPT program (CPT-7) conducted through the National Center for Veterans Studies.
The program involved one daily individual CPT-7 session with a mental health provider in the morning followed by optional group recreational activities in the afternoon. Twelve military personnel in two cohorts with either PTSD or subthreshold PTSD, defined as having all but one symptom cluster present, were included in the study.
Keep patients engaged
Preliminary results showed reductions in PCL-5 scores from pre- to posttreatment of approximately 40% (P < .001).
“Just over 50% of patients left [the program] with symptoms below probable PTSD diagnosis on a self-report measure,” Dr. Rozek said.
Importantly, none of the participants dropped out of the treatment, but Dr. Rozek said that this was not necessarily surprising because of the nature of the program.
“These patients are brought in as a cohort and form some bonds, as they all have experienced traumatic events, although often [they have had] very different traumas,” he said.
“We’ve found that by doing daily treatment, it is more accessible and removes barriers, as it is often easier to take a week or a few weeks off at a time and participate in treatment than the logistics of weekly treatment,” he added.
Dr. Rozek said he suspects two key factors may predict treatment response in such programs – cognitive flexibility and emotion regulation.
“Patients who come into treatment and are extremely rigid in their thinking and are unable to manage their emotions may be slower to respond to treatment,” he noted.
“That being said, there are a variety of treatments that target these factors in different ways. Now we need to do the work to determine which treatments work for whom.”
The findings on longer-term durability of rapid improvement bode well for the program. “Although the work in treatment is hard, they patients really start to see the gains quickly, within a week or weeks instead of months,” Dr. Rozek said.
“This is rewarding in itself, and I would say is a strong factor for keeping patients engaged,” he concluded.
Dr. Rozek has received research funding from the National Institutes of Health, the Department of Defense, the Bob Woodruff Foundation, and the Boeing Corporation.
A version of this article originally appeared on Medscape.com.
IV esketamine, ketamine equally effective for resistant depression
Intravenous (IV) esketamine is as safe and effective as IV ketamine for patients with treatment-resistant depression, new research suggests.
“Our study was the first randomized clinical trial directly comparing ketamine and esketamine in treatment-resistant depression,” senior investigator Lucas C. Quarantini, MD, PhD, division of psychiatry, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil, said in an interview.
The findings showed that esketamine was not inferior to ketamine in remission of depressive symptoms 24 hours after a single IV dose, and the two treatments had similar side effect profiles, Dr. Quarantini said.
Furthermore, “our results showed that only the number of treatment failures was an important factor for the remission of symptoms,” he added.
The findings were scheduled to be presented at the Anxiety and Depression Association of America (ADAA) Conference 2020, along with publication in the Journal of Affective Disorders (2020 Mar 1;264:527-34). However, the ADAA conference was canceled in the wake of the coronavirus pandemic.
More treatment options
The randomized, double-blind noninferiority trial compared IV racemic ketamine and esketamine, two formulations of the glutamate NMDA receptor modulator drug. It included 63 participants (61.9% women; mean age, 47 years) with treatment-resistant major depressive disorder, as determined by DSM-5 criteria.
Participants were enrolled between March 2017 and June 2018 and randomized to receive a single subanesthetic dose of racemic ketamine (0.5 mg/kg; n = 29) or esketamine (0.25 mg/kg; n = 34) for 40 minutes.
Results showed esketamine to be noninferior to ketamine as determined by the Montgomery-Åsberg Depression Rating Scale (MADRS).
The difference of just 5.3% confirmed noninferiority.
Although ketamine showed a tendency to have a longer-lasting antidepressant effect compared with esketamine, the difference did not reach statistical significance and should be evaluated in future studies, the investigators noted.
Both treatments were safe and well tolerated. Consistent with previous studies, the most frequent side effects were dissociative symptoms, including derealization, depersonalization, and cardiovascular changes, and increased blood pressure and heart rate, which occurred equally in both groups. There were no serious adverse events in either study group.
The investigators noted that most of the previous research examining antidepressant effects of ketamine has used the IV racemic type. The current findings are particularly important for situations in which ketamine or intranasal esketamine, which was recently approved by the Food and Drug Administration, are unavailable, Dr. Quarantini said.
“What our study adds to what has been previously published is that the only way to really analyze if two drugs are equivalent is to compare them in a head-to-head trial; and that was what we did,” he said.
“Our findings bring a greater basis for practitioners from locations where intravenous esketamine is more easily obtainable than ketamine to use it as an affordable option for treating depressive patients,” Dr. Quarantini added.
“Since this [lack of availability] is the scenario here in Brazil, and probably in many other countries, all patients from these locations will benefit from this finding,” he said.
While further evaluating the study results to determine which clinical characteristics were predictive of remission of depressive symptoms, the researchers assessed several key factors. The median duration of disease progression was 12 months, median number of depressive episodes was five, and median number of therapeutic treatment failures was three.
The investigators also looked at the number of suicide attempts and degree of dissociative behavior.
Of these factors, the number of therapeutic failures was the only significant predictor of symptom remission, with an odds ratio of 1.46 for each prior therapeutic failure (95% CI, 1.08-1.99).
“To date, we have not found [other] studies with similar data,” Dr. Quarantini noted.
“Identifying remission predictors may contribute to selecting more suitable candidates for the intervention and result in more individualized and effective patient management,” the investigators wrote.
Consistent findings
Commenting on the findings, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Conn., noted that key study limitations include the small sample size and lack of a placebo group.
Nevertheless, “I think it is fair to say that it is unlikely that the treatments are markedly different in their effects on depression over 24 hours,” he said in an interview.
Dr. Sanacora, director of the Yale Depression Research Program, was not involved with the current research.
The findings are “consistent with what we can extrapolate from other clinical trials examining racemic ketamine and esketamine separately,” he said.
Dr. Sanacora noted that because esketamine has been previously shown to be a more potent anesthetic than arketamine, the other component of racemic ketamine, it is “the primary form of ketamine used as an anesthetic agent in several regions of the world with the idea that it may be more selective for the desired anesthetic effect.”
Even with its limitations, the study does offer some notable yet preliminary insights, he added.
“It is interesting to see varying degrees of numerical differences between the two treatments at different time points,” Dr. Sanacora said. In addition, “there may be some differing effects between the two treatments over time, but we really do not have enough data to say much of anything [about that] with confidence at this point.”
The study was supported by the Programa de Pesquisa para o SUS through Fundação de Amparo à Pesquisa do Estado da Bahia. Dr. Quarantini has reported receiving consulting fees from Allergan, Abbott, Janssen Pharmaceuticals, and Lundbeck, and research fees from Janssen Pharmaceuticals. The other study authors’ disclosures are listed in the published article. Dr. Sanacora has reported consulting and/or conducting research from several pharmaceutical companies. He also holds shares in BioHaven Pharmaceuticals and is coinventor on a patent called “Glutamate Agents in the Treatment of Mental Disorders.”
A version of this article originally appeared on Medscape.com.
Intravenous (IV) esketamine is as safe and effective as IV ketamine for patients with treatment-resistant depression, new research suggests.
“Our study was the first randomized clinical trial directly comparing ketamine and esketamine in treatment-resistant depression,” senior investigator Lucas C. Quarantini, MD, PhD, division of psychiatry, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil, said in an interview.
The findings showed that esketamine was not inferior to ketamine in remission of depressive symptoms 24 hours after a single IV dose, and the two treatments had similar side effect profiles, Dr. Quarantini said.
Furthermore, “our results showed that only the number of treatment failures was an important factor for the remission of symptoms,” he added.
The findings were scheduled to be presented at the Anxiety and Depression Association of America (ADAA) Conference 2020, along with publication in the Journal of Affective Disorders (2020 Mar 1;264:527-34). However, the ADAA conference was canceled in the wake of the coronavirus pandemic.
More treatment options
The randomized, double-blind noninferiority trial compared IV racemic ketamine and esketamine, two formulations of the glutamate NMDA receptor modulator drug. It included 63 participants (61.9% women; mean age, 47 years) with treatment-resistant major depressive disorder, as determined by DSM-5 criteria.
Participants were enrolled between March 2017 and June 2018 and randomized to receive a single subanesthetic dose of racemic ketamine (0.5 mg/kg; n = 29) or esketamine (0.25 mg/kg; n = 34) for 40 minutes.
Results showed esketamine to be noninferior to ketamine as determined by the Montgomery-Åsberg Depression Rating Scale (MADRS).
The difference of just 5.3% confirmed noninferiority.
Although ketamine showed a tendency to have a longer-lasting antidepressant effect compared with esketamine, the difference did not reach statistical significance and should be evaluated in future studies, the investigators noted.
Both treatments were safe and well tolerated. Consistent with previous studies, the most frequent side effects were dissociative symptoms, including derealization, depersonalization, and cardiovascular changes, and increased blood pressure and heart rate, which occurred equally in both groups. There were no serious adverse events in either study group.
The investigators noted that most of the previous research examining antidepressant effects of ketamine has used the IV racemic type. The current findings are particularly important for situations in which ketamine or intranasal esketamine, which was recently approved by the Food and Drug Administration, are unavailable, Dr. Quarantini said.
“What our study adds to what has been previously published is that the only way to really analyze if two drugs are equivalent is to compare them in a head-to-head trial; and that was what we did,” he said.
“Our findings bring a greater basis for practitioners from locations where intravenous esketamine is more easily obtainable than ketamine to use it as an affordable option for treating depressive patients,” Dr. Quarantini added.
“Since this [lack of availability] is the scenario here in Brazil, and probably in many other countries, all patients from these locations will benefit from this finding,” he said.
While further evaluating the study results to determine which clinical characteristics were predictive of remission of depressive symptoms, the researchers assessed several key factors. The median duration of disease progression was 12 months, median number of depressive episodes was five, and median number of therapeutic treatment failures was three.
The investigators also looked at the number of suicide attempts and degree of dissociative behavior.
Of these factors, the number of therapeutic failures was the only significant predictor of symptom remission, with an odds ratio of 1.46 for each prior therapeutic failure (95% CI, 1.08-1.99).
“To date, we have not found [other] studies with similar data,” Dr. Quarantini noted.
“Identifying remission predictors may contribute to selecting more suitable candidates for the intervention and result in more individualized and effective patient management,” the investigators wrote.
Consistent findings
Commenting on the findings, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Conn., noted that key study limitations include the small sample size and lack of a placebo group.
Nevertheless, “I think it is fair to say that it is unlikely that the treatments are markedly different in their effects on depression over 24 hours,” he said in an interview.
Dr. Sanacora, director of the Yale Depression Research Program, was not involved with the current research.
The findings are “consistent with what we can extrapolate from other clinical trials examining racemic ketamine and esketamine separately,” he said.
Dr. Sanacora noted that because esketamine has been previously shown to be a more potent anesthetic than arketamine, the other component of racemic ketamine, it is “the primary form of ketamine used as an anesthetic agent in several regions of the world with the idea that it may be more selective for the desired anesthetic effect.”
Even with its limitations, the study does offer some notable yet preliminary insights, he added.
“It is interesting to see varying degrees of numerical differences between the two treatments at different time points,” Dr. Sanacora said. In addition, “there may be some differing effects between the two treatments over time, but we really do not have enough data to say much of anything [about that] with confidence at this point.”
The study was supported by the Programa de Pesquisa para o SUS through Fundação de Amparo à Pesquisa do Estado da Bahia. Dr. Quarantini has reported receiving consulting fees from Allergan, Abbott, Janssen Pharmaceuticals, and Lundbeck, and research fees from Janssen Pharmaceuticals. The other study authors’ disclosures are listed in the published article. Dr. Sanacora has reported consulting and/or conducting research from several pharmaceutical companies. He also holds shares in BioHaven Pharmaceuticals and is coinventor on a patent called “Glutamate Agents in the Treatment of Mental Disorders.”
A version of this article originally appeared on Medscape.com.
Intravenous (IV) esketamine is as safe and effective as IV ketamine for patients with treatment-resistant depression, new research suggests.
“Our study was the first randomized clinical trial directly comparing ketamine and esketamine in treatment-resistant depression,” senior investigator Lucas C. Quarantini, MD, PhD, division of psychiatry, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil, said in an interview.
The findings showed that esketamine was not inferior to ketamine in remission of depressive symptoms 24 hours after a single IV dose, and the two treatments had similar side effect profiles, Dr. Quarantini said.
Furthermore, “our results showed that only the number of treatment failures was an important factor for the remission of symptoms,” he added.
The findings were scheduled to be presented at the Anxiety and Depression Association of America (ADAA) Conference 2020, along with publication in the Journal of Affective Disorders (2020 Mar 1;264:527-34). However, the ADAA conference was canceled in the wake of the coronavirus pandemic.
More treatment options
The randomized, double-blind noninferiority trial compared IV racemic ketamine and esketamine, two formulations of the glutamate NMDA receptor modulator drug. It included 63 participants (61.9% women; mean age, 47 years) with treatment-resistant major depressive disorder, as determined by DSM-5 criteria.
Participants were enrolled between March 2017 and June 2018 and randomized to receive a single subanesthetic dose of racemic ketamine (0.5 mg/kg; n = 29) or esketamine (0.25 mg/kg; n = 34) for 40 minutes.
Results showed esketamine to be noninferior to ketamine as determined by the Montgomery-Åsberg Depression Rating Scale (MADRS).
The difference of just 5.3% confirmed noninferiority.
Although ketamine showed a tendency to have a longer-lasting antidepressant effect compared with esketamine, the difference did not reach statistical significance and should be evaluated in future studies, the investigators noted.
Both treatments were safe and well tolerated. Consistent with previous studies, the most frequent side effects were dissociative symptoms, including derealization, depersonalization, and cardiovascular changes, and increased blood pressure and heart rate, which occurred equally in both groups. There were no serious adverse events in either study group.
The investigators noted that most of the previous research examining antidepressant effects of ketamine has used the IV racemic type. The current findings are particularly important for situations in which ketamine or intranasal esketamine, which was recently approved by the Food and Drug Administration, are unavailable, Dr. Quarantini said.
“What our study adds to what has been previously published is that the only way to really analyze if two drugs are equivalent is to compare them in a head-to-head trial; and that was what we did,” he said.
“Our findings bring a greater basis for practitioners from locations where intravenous esketamine is more easily obtainable than ketamine to use it as an affordable option for treating depressive patients,” Dr. Quarantini added.
“Since this [lack of availability] is the scenario here in Brazil, and probably in many other countries, all patients from these locations will benefit from this finding,” he said.
While further evaluating the study results to determine which clinical characteristics were predictive of remission of depressive symptoms, the researchers assessed several key factors. The median duration of disease progression was 12 months, median number of depressive episodes was five, and median number of therapeutic treatment failures was three.
The investigators also looked at the number of suicide attempts and degree of dissociative behavior.
Of these factors, the number of therapeutic failures was the only significant predictor of symptom remission, with an odds ratio of 1.46 for each prior therapeutic failure (95% CI, 1.08-1.99).
“To date, we have not found [other] studies with similar data,” Dr. Quarantini noted.
“Identifying remission predictors may contribute to selecting more suitable candidates for the intervention and result in more individualized and effective patient management,” the investigators wrote.
Consistent findings
Commenting on the findings, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Conn., noted that key study limitations include the small sample size and lack of a placebo group.
Nevertheless, “I think it is fair to say that it is unlikely that the treatments are markedly different in their effects on depression over 24 hours,” he said in an interview.
Dr. Sanacora, director of the Yale Depression Research Program, was not involved with the current research.
The findings are “consistent with what we can extrapolate from other clinical trials examining racemic ketamine and esketamine separately,” he said.
Dr. Sanacora noted that because esketamine has been previously shown to be a more potent anesthetic than arketamine, the other component of racemic ketamine, it is “the primary form of ketamine used as an anesthetic agent in several regions of the world with the idea that it may be more selective for the desired anesthetic effect.”
Even with its limitations, the study does offer some notable yet preliminary insights, he added.
“It is interesting to see varying degrees of numerical differences between the two treatments at different time points,” Dr. Sanacora said. In addition, “there may be some differing effects between the two treatments over time, but we really do not have enough data to say much of anything [about that] with confidence at this point.”
The study was supported by the Programa de Pesquisa para o SUS through Fundação de Amparo à Pesquisa do Estado da Bahia. Dr. Quarantini has reported receiving consulting fees from Allergan, Abbott, Janssen Pharmaceuticals, and Lundbeck, and research fees from Janssen Pharmaceuticals. The other study authors’ disclosures are listed in the published article. Dr. Sanacora has reported consulting and/or conducting research from several pharmaceutical companies. He also holds shares in BioHaven Pharmaceuticals and is coinventor on a patent called “Glutamate Agents in the Treatment of Mental Disorders.”
A version of this article originally appeared on Medscape.com.
First guidelines to address thyroid disease surgery
offering evidence-based recommendations on the wide-ranging aspects of thyroidectomy and the management of benign, as well as malignant, thyroid nodules and cancer.
Whereas various endocrine and thyroid societies issue guidelines on many aspects of the management of thyroid disease, the new AAES guidelines are the first specifically to address surgical management of thyroid disease in adults.
“These guidelines truly focus on the surgical decision-making and management of thyroid disease. However, there is something for all clinicians who take care of patients with thyroid disease,” lead author Kepal N. Patel, MD, of NYU Langone Health in New York City, said in an interview.
The guidelines, published in the Annals of Surgery, include a total of 66 recommendations from a multidisciplinary panel of 19 experts who reviewed medical literature spanning 1985-2018.
More than 100,000 thyroidectomies are performed each year in the United States alone, and as surgical indications and treatment paradigms evolve, the need for surgical guidance is more important than ever, Dr. Patel said.
“Such transformations have propagated differences in clinical interpretation and management, and as a result, clinical uncertainty, and even controversy, have emerged,” he said. “Recognizing the importance of these changes, the AAES determined that evidence-based clinical guidelines were necessary to enhance the safe and effective surgical treatment of benign and malignant thyroid disease.”
Key areas addressed in the guidelines include the addition of new cytologic and pathologic diagnostic criteria, molecular profiling tests, operative techniques, and adjuncts, as well as the nuances surrounding the sometimes challenging newer concept of “borderline” thyroid tumors, Dr. Patel noted.
In terms of imaging recommendations, for instance, the guidelines recommend the preoperative use of computed tomography or magnetic resonance imaging, as stated in Recommendation 6: “CT or MRI with intravenous contrast should be used preoperatively as an adjunct to ultrasound in selected patients with clinical suspicion for advanced locoregional thyroid cancer.” The recommendation is cited as being “strong,” with a “low quality of evidence.”
Further diagnostic recommendations cover issues that include voice assessment, the risk for vocal fold dysfunction related to thyroid disease and surgery, and the use of fine-needle aspiration biopsy in evaluating suspicious thyroid nodules and lymph nodes.
The guidelines also address the indications for thyroidectomy, with recommendations regarding the extent and outcomes of surgery spanning different categories of thyroid disease. A key recommendation along those lines, for instance, indicates that, when possible, thyroidectomy should be performed by surgeons who perform a high volume of such procedures.
Approaches for safe and effective perioperative management are also covered, and include measures to prevent complications and the use of thyroid tissue diagnosis during surgery, such as core-needle biopsy of the thyroid and cervical lymph nodes, and incisional biopsy of the thyroid, nodal dissection, and concurrent parathyroidectomy.
Other recommendations address the optimal management of thyroid cancer, with an emphasis on a personalized, evidence-based approach tailored to the patient’s situation and preferences.
The authors underscored that, as technology rapidly evolves, “in the future, this work will certainly and rightly need to be done again.” In the meantime, they wrote, recommendations should be relevant to “the target audience [of] the practicing surgeon in a community hospital, academic center, or training program.”
An AAES press release noted that “the members of the expert panel hope their efforts will meet the need for evidence-based recommendations to ‘define practice, personalize care, stratify risk, reduce health care costs, improve outcomes, and identify rational challenges for future efforts.’ ”
The authors of the guidelines reported no conflicts of interest in regard to the guidelines, although the article lists disclosures for six authors.
This article first appeared on Medscape.com.
offering evidence-based recommendations on the wide-ranging aspects of thyroidectomy and the management of benign, as well as malignant, thyroid nodules and cancer.
Whereas various endocrine and thyroid societies issue guidelines on many aspects of the management of thyroid disease, the new AAES guidelines are the first specifically to address surgical management of thyroid disease in adults.
“These guidelines truly focus on the surgical decision-making and management of thyroid disease. However, there is something for all clinicians who take care of patients with thyroid disease,” lead author Kepal N. Patel, MD, of NYU Langone Health in New York City, said in an interview.
The guidelines, published in the Annals of Surgery, include a total of 66 recommendations from a multidisciplinary panel of 19 experts who reviewed medical literature spanning 1985-2018.
More than 100,000 thyroidectomies are performed each year in the United States alone, and as surgical indications and treatment paradigms evolve, the need for surgical guidance is more important than ever, Dr. Patel said.
“Such transformations have propagated differences in clinical interpretation and management, and as a result, clinical uncertainty, and even controversy, have emerged,” he said. “Recognizing the importance of these changes, the AAES determined that evidence-based clinical guidelines were necessary to enhance the safe and effective surgical treatment of benign and malignant thyroid disease.”
Key areas addressed in the guidelines include the addition of new cytologic and pathologic diagnostic criteria, molecular profiling tests, operative techniques, and adjuncts, as well as the nuances surrounding the sometimes challenging newer concept of “borderline” thyroid tumors, Dr. Patel noted.
In terms of imaging recommendations, for instance, the guidelines recommend the preoperative use of computed tomography or magnetic resonance imaging, as stated in Recommendation 6: “CT or MRI with intravenous contrast should be used preoperatively as an adjunct to ultrasound in selected patients with clinical suspicion for advanced locoregional thyroid cancer.” The recommendation is cited as being “strong,” with a “low quality of evidence.”
Further diagnostic recommendations cover issues that include voice assessment, the risk for vocal fold dysfunction related to thyroid disease and surgery, and the use of fine-needle aspiration biopsy in evaluating suspicious thyroid nodules and lymph nodes.
The guidelines also address the indications for thyroidectomy, with recommendations regarding the extent and outcomes of surgery spanning different categories of thyroid disease. A key recommendation along those lines, for instance, indicates that, when possible, thyroidectomy should be performed by surgeons who perform a high volume of such procedures.
Approaches for safe and effective perioperative management are also covered, and include measures to prevent complications and the use of thyroid tissue diagnosis during surgery, such as core-needle biopsy of the thyroid and cervical lymph nodes, and incisional biopsy of the thyroid, nodal dissection, and concurrent parathyroidectomy.
Other recommendations address the optimal management of thyroid cancer, with an emphasis on a personalized, evidence-based approach tailored to the patient’s situation and preferences.
The authors underscored that, as technology rapidly evolves, “in the future, this work will certainly and rightly need to be done again.” In the meantime, they wrote, recommendations should be relevant to “the target audience [of] the practicing surgeon in a community hospital, academic center, or training program.”
An AAES press release noted that “the members of the expert panel hope their efforts will meet the need for evidence-based recommendations to ‘define practice, personalize care, stratify risk, reduce health care costs, improve outcomes, and identify rational challenges for future efforts.’ ”
The authors of the guidelines reported no conflicts of interest in regard to the guidelines, although the article lists disclosures for six authors.
This article first appeared on Medscape.com.
offering evidence-based recommendations on the wide-ranging aspects of thyroidectomy and the management of benign, as well as malignant, thyroid nodules and cancer.
Whereas various endocrine and thyroid societies issue guidelines on many aspects of the management of thyroid disease, the new AAES guidelines are the first specifically to address surgical management of thyroid disease in adults.
“These guidelines truly focus on the surgical decision-making and management of thyroid disease. However, there is something for all clinicians who take care of patients with thyroid disease,” lead author Kepal N. Patel, MD, of NYU Langone Health in New York City, said in an interview.
The guidelines, published in the Annals of Surgery, include a total of 66 recommendations from a multidisciplinary panel of 19 experts who reviewed medical literature spanning 1985-2018.
More than 100,000 thyroidectomies are performed each year in the United States alone, and as surgical indications and treatment paradigms evolve, the need for surgical guidance is more important than ever, Dr. Patel said.
“Such transformations have propagated differences in clinical interpretation and management, and as a result, clinical uncertainty, and even controversy, have emerged,” he said. “Recognizing the importance of these changes, the AAES determined that evidence-based clinical guidelines were necessary to enhance the safe and effective surgical treatment of benign and malignant thyroid disease.”
Key areas addressed in the guidelines include the addition of new cytologic and pathologic diagnostic criteria, molecular profiling tests, operative techniques, and adjuncts, as well as the nuances surrounding the sometimes challenging newer concept of “borderline” thyroid tumors, Dr. Patel noted.
In terms of imaging recommendations, for instance, the guidelines recommend the preoperative use of computed tomography or magnetic resonance imaging, as stated in Recommendation 6: “CT or MRI with intravenous contrast should be used preoperatively as an adjunct to ultrasound in selected patients with clinical suspicion for advanced locoregional thyroid cancer.” The recommendation is cited as being “strong,” with a “low quality of evidence.”
Further diagnostic recommendations cover issues that include voice assessment, the risk for vocal fold dysfunction related to thyroid disease and surgery, and the use of fine-needle aspiration biopsy in evaluating suspicious thyroid nodules and lymph nodes.
The guidelines also address the indications for thyroidectomy, with recommendations regarding the extent and outcomes of surgery spanning different categories of thyroid disease. A key recommendation along those lines, for instance, indicates that, when possible, thyroidectomy should be performed by surgeons who perform a high volume of such procedures.
Approaches for safe and effective perioperative management are also covered, and include measures to prevent complications and the use of thyroid tissue diagnosis during surgery, such as core-needle biopsy of the thyroid and cervical lymph nodes, and incisional biopsy of the thyroid, nodal dissection, and concurrent parathyroidectomy.
Other recommendations address the optimal management of thyroid cancer, with an emphasis on a personalized, evidence-based approach tailored to the patient’s situation and preferences.
The authors underscored that, as technology rapidly evolves, “in the future, this work will certainly and rightly need to be done again.” In the meantime, they wrote, recommendations should be relevant to “the target audience [of] the practicing surgeon in a community hospital, academic center, or training program.”
An AAES press release noted that “the members of the expert panel hope their efforts will meet the need for evidence-based recommendations to ‘define practice, personalize care, stratify risk, reduce health care costs, improve outcomes, and identify rational challenges for future efforts.’ ”
The authors of the guidelines reported no conflicts of interest in regard to the guidelines, although the article lists disclosures for six authors.
This article first appeared on Medscape.com.
Shared medical appointments educate and encourage MS patients
WEST PALM BEACH, FLA. – according to a presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis.
“At first, this may sound to patients like an awkward concept – they may say, ‘Why would I want to have a medical appointment with other people?’ ” Mary R. Rensel, MD, who is the director of the program at the Mellen Center for Multiple Sclerosis, Cleveland Clinic Foundation, said. “But once they get there, it’s wonderful to see what happens – patients start to encourage each other and share resources, and it’s enjoyable for the patients and providers alike,” she said.
The main objective of the shared appointments concept was to increase education regarding comorbidity prevention and management of MS, however, importantly, if patients wish to discuss any issues privately, they are accommodated. In addition, family members, children, and caregivers are all welcome to attend. “Caregivers need support as well, so their participation is welcome,” Dr. Rensel said.
A significant benefit of the program is the extended time with providers – an hour and a half – which is a substantially longer period than patients and providers typically spend together, Dr. Rensel noted. “Medical visits are often so rushed, but this gives us much more time together, to learn more and talk about things like brain health,” she said.
With guidance from a multidisciplinary team including nurses, wellness providers, psychologists, and other experts, there are currently seven meeting themes that are rotated through the year, focusing on a variety of subjects. One, for instance, includes education from a nutritionist, and the center includes a kitchen for the group to learn about and try recipes. Other sessions include chair yoga, art therapy, guided imagery, and exercise physiology.
The Cleveland Clinic is a leader in the concept of SMA and offers it to as many as 360 disease states. With the pilot program now underway for more than 3 years, Dr. Rensel and her team conducted a study to investigate its effects.
For the study, the authors collected clinical data on 50 patients who had attended at least one session between January 2016 and June 2019. Among the patients, 94% were female, 80% had relapsing-remitting MS, and mean age was 50. Patients had a mean Determined Disease Steps (PDSS) score of 3.1 plus or minus 2.4 and the average 25-foot walk and nine-hole peg test (dominant hand) times were 9.4 plus or minus 7.8 seconds and 25.8 plus or minus 9.1 seconds, respectively.
The most common comorbidity was depression/anxiety, occurring in 44% of patients, however after participation in the shared medical appointment program, their mean Patient Health Questionnaire-9 scores, with higher scores indicative of worse depression, decreased from pretreatment scores of 7.3 plus or minus 5.5 to posttreatment scores of 5.1 plus or minus 5.6 (P = .001).
Notably, the program appears to have had a positive effect on patients’ use of health care services – while there was a significant decrease in the mean number of emergency room visits (n = 13 to n = 2; P = .0005), the results showed a favorable increase in mean number of follow-up visits with attendees’ primary care providers (n = 19 to n = 41; P = 3.47), physical therapists (n = 15 to n = 27; P = .004), or psychologists (n = 6 to n = 19; P = .003).
“The study was to evaluate the effect of the program after even just one appointment, and we found it really seemed to increase the use of more appropriate care, with less ER utilization and more visits to primary care,” Dr. Rensel said. The study even showed a small but significant reduction in pre- and postoutcome body mass index (BMI, 30.2 plus or minus 7.3 vs. 28.8 plus or minus 7.1; P = .03).
A critical metric that was not measured in the study – the effect of social interaction and camaraderie in a condition that can, for many, feel socially isolating – is clearly profound, Dr. Rensel said.
Amar Dhand, MD, associate professor of neurology at Brigham and Women’s Hospital, Harvard University, Boston, agreed that the peer support in such medical group settings can be highly valuable.
“Shared medical appointments offer an opportunity for peer-to-peer engagement, support, and education,” he said in an interview. “For many patients, this is a chance to bond with persons who are coexperiencing similar problems, allowing new social connections to emerge.”
Dr. Dhand, who spoke on the issue of the importance of social networks at the meeting, noted that, although there are numerous benefits with shared medical appointments, not all patients may respond well.
“Health care settings are one place to stimulate community among peers. This is one important ingredient of addressing social isolation,” he said. “However, there remain challenges such as sustainability of such relationships, paradoxical depression when persons see others with more severe disease, and infrastructure to support such programs.”
The findings from the study, however, do suggest favorable responses, he noted.
“I think, mechanistically, improved psychosocial outcomes are the most pertinent to the intervention,” Dr. Dhand said. “The health care utilization may be attributed to other factors and will need to be assessed in a case control design.”
Key benefits of the shared medical appointment concept
A recent article from Cleveland Clinic researchers reviewing the concept of shared medical appointments summarizes that the programs offer benefits based on nine key principles:
- Group exposure in shared medical appointments combats isolation, which in turn helps to remove doubts about one’s ability to manage illness.
- Patients learn about disease self-management vicariously by witnessing others’ illness experiences.
- Patients feel inspired by seeing others who are coping well.
- Group dynamics lead patients and providers to developing more equitable relationships.
- Providers feel increased appreciation and rapport toward colleagues leading to increased efficiency.
- Providers learn from the patients how better to meet their patients’ needs.
- Adequate time allotment of the SMA leads patients to feel supported.
- Patients receive professional expertise from the provider in combination with firsthand information from peers, resulting in more robust health knowledge.
- Patients have the opportunity to see how the physicians interact with fellow patients, which allows them to get to know the physician and better determine their level of trust.
The take-home message from the shared medical appointments concept is that “it may hit a quadruple aim,” Dr. Rensel said. “Access, cost, outcomes, and provider satisfaction.”
The Shared Medical Appointments program received a grant from Genzyme. Dr. Rensel reported consulting or advisory board relationships with Serono, Biogen, Teva, Genzyme, Novartis, and the National Multiple Sclerosis Society. Dr. Dhand had no disclosures to report.
WEST PALM BEACH, FLA. – according to a presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis.
“At first, this may sound to patients like an awkward concept – they may say, ‘Why would I want to have a medical appointment with other people?’ ” Mary R. Rensel, MD, who is the director of the program at the Mellen Center for Multiple Sclerosis, Cleveland Clinic Foundation, said. “But once they get there, it’s wonderful to see what happens – patients start to encourage each other and share resources, and it’s enjoyable for the patients and providers alike,” she said.
The main objective of the shared appointments concept was to increase education regarding comorbidity prevention and management of MS, however, importantly, if patients wish to discuss any issues privately, they are accommodated. In addition, family members, children, and caregivers are all welcome to attend. “Caregivers need support as well, so their participation is welcome,” Dr. Rensel said.
A significant benefit of the program is the extended time with providers – an hour and a half – which is a substantially longer period than patients and providers typically spend together, Dr. Rensel noted. “Medical visits are often so rushed, but this gives us much more time together, to learn more and talk about things like brain health,” she said.
With guidance from a multidisciplinary team including nurses, wellness providers, psychologists, and other experts, there are currently seven meeting themes that are rotated through the year, focusing on a variety of subjects. One, for instance, includes education from a nutritionist, and the center includes a kitchen for the group to learn about and try recipes. Other sessions include chair yoga, art therapy, guided imagery, and exercise physiology.
The Cleveland Clinic is a leader in the concept of SMA and offers it to as many as 360 disease states. With the pilot program now underway for more than 3 years, Dr. Rensel and her team conducted a study to investigate its effects.
For the study, the authors collected clinical data on 50 patients who had attended at least one session between January 2016 and June 2019. Among the patients, 94% were female, 80% had relapsing-remitting MS, and mean age was 50. Patients had a mean Determined Disease Steps (PDSS) score of 3.1 plus or minus 2.4 and the average 25-foot walk and nine-hole peg test (dominant hand) times were 9.4 plus or minus 7.8 seconds and 25.8 plus or minus 9.1 seconds, respectively.
The most common comorbidity was depression/anxiety, occurring in 44% of patients, however after participation in the shared medical appointment program, their mean Patient Health Questionnaire-9 scores, with higher scores indicative of worse depression, decreased from pretreatment scores of 7.3 plus or minus 5.5 to posttreatment scores of 5.1 plus or minus 5.6 (P = .001).
Notably, the program appears to have had a positive effect on patients’ use of health care services – while there was a significant decrease in the mean number of emergency room visits (n = 13 to n = 2; P = .0005), the results showed a favorable increase in mean number of follow-up visits with attendees’ primary care providers (n = 19 to n = 41; P = 3.47), physical therapists (n = 15 to n = 27; P = .004), or psychologists (n = 6 to n = 19; P = .003).
“The study was to evaluate the effect of the program after even just one appointment, and we found it really seemed to increase the use of more appropriate care, with less ER utilization and more visits to primary care,” Dr. Rensel said. The study even showed a small but significant reduction in pre- and postoutcome body mass index (BMI, 30.2 plus or minus 7.3 vs. 28.8 plus or minus 7.1; P = .03).
A critical metric that was not measured in the study – the effect of social interaction and camaraderie in a condition that can, for many, feel socially isolating – is clearly profound, Dr. Rensel said.
Amar Dhand, MD, associate professor of neurology at Brigham and Women’s Hospital, Harvard University, Boston, agreed that the peer support in such medical group settings can be highly valuable.
“Shared medical appointments offer an opportunity for peer-to-peer engagement, support, and education,” he said in an interview. “For many patients, this is a chance to bond with persons who are coexperiencing similar problems, allowing new social connections to emerge.”
Dr. Dhand, who spoke on the issue of the importance of social networks at the meeting, noted that, although there are numerous benefits with shared medical appointments, not all patients may respond well.
“Health care settings are one place to stimulate community among peers. This is one important ingredient of addressing social isolation,” he said. “However, there remain challenges such as sustainability of such relationships, paradoxical depression when persons see others with more severe disease, and infrastructure to support such programs.”
The findings from the study, however, do suggest favorable responses, he noted.
“I think, mechanistically, improved psychosocial outcomes are the most pertinent to the intervention,” Dr. Dhand said. “The health care utilization may be attributed to other factors and will need to be assessed in a case control design.”
Key benefits of the shared medical appointment concept
A recent article from Cleveland Clinic researchers reviewing the concept of shared medical appointments summarizes that the programs offer benefits based on nine key principles:
- Group exposure in shared medical appointments combats isolation, which in turn helps to remove doubts about one’s ability to manage illness.
- Patients learn about disease self-management vicariously by witnessing others’ illness experiences.
- Patients feel inspired by seeing others who are coping well.
- Group dynamics lead patients and providers to developing more equitable relationships.
- Providers feel increased appreciation and rapport toward colleagues leading to increased efficiency.
- Providers learn from the patients how better to meet their patients’ needs.
- Adequate time allotment of the SMA leads patients to feel supported.
- Patients receive professional expertise from the provider in combination with firsthand information from peers, resulting in more robust health knowledge.
- Patients have the opportunity to see how the physicians interact with fellow patients, which allows them to get to know the physician and better determine their level of trust.
The take-home message from the shared medical appointments concept is that “it may hit a quadruple aim,” Dr. Rensel said. “Access, cost, outcomes, and provider satisfaction.”
The Shared Medical Appointments program received a grant from Genzyme. Dr. Rensel reported consulting or advisory board relationships with Serono, Biogen, Teva, Genzyme, Novartis, and the National Multiple Sclerosis Society. Dr. Dhand had no disclosures to report.
WEST PALM BEACH, FLA. – according to a presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis.
“At first, this may sound to patients like an awkward concept – they may say, ‘Why would I want to have a medical appointment with other people?’ ” Mary R. Rensel, MD, who is the director of the program at the Mellen Center for Multiple Sclerosis, Cleveland Clinic Foundation, said. “But once they get there, it’s wonderful to see what happens – patients start to encourage each other and share resources, and it’s enjoyable for the patients and providers alike,” she said.
The main objective of the shared appointments concept was to increase education regarding comorbidity prevention and management of MS, however, importantly, if patients wish to discuss any issues privately, they are accommodated. In addition, family members, children, and caregivers are all welcome to attend. “Caregivers need support as well, so their participation is welcome,” Dr. Rensel said.
A significant benefit of the program is the extended time with providers – an hour and a half – which is a substantially longer period than patients and providers typically spend together, Dr. Rensel noted. “Medical visits are often so rushed, but this gives us much more time together, to learn more and talk about things like brain health,” she said.
With guidance from a multidisciplinary team including nurses, wellness providers, psychologists, and other experts, there are currently seven meeting themes that are rotated through the year, focusing on a variety of subjects. One, for instance, includes education from a nutritionist, and the center includes a kitchen for the group to learn about and try recipes. Other sessions include chair yoga, art therapy, guided imagery, and exercise physiology.
The Cleveland Clinic is a leader in the concept of SMA and offers it to as many as 360 disease states. With the pilot program now underway for more than 3 years, Dr. Rensel and her team conducted a study to investigate its effects.
For the study, the authors collected clinical data on 50 patients who had attended at least one session between January 2016 and June 2019. Among the patients, 94% were female, 80% had relapsing-remitting MS, and mean age was 50. Patients had a mean Determined Disease Steps (PDSS) score of 3.1 plus or minus 2.4 and the average 25-foot walk and nine-hole peg test (dominant hand) times were 9.4 plus or minus 7.8 seconds and 25.8 plus or minus 9.1 seconds, respectively.
The most common comorbidity was depression/anxiety, occurring in 44% of patients, however after participation in the shared medical appointment program, their mean Patient Health Questionnaire-9 scores, with higher scores indicative of worse depression, decreased from pretreatment scores of 7.3 plus or minus 5.5 to posttreatment scores of 5.1 plus or minus 5.6 (P = .001).
Notably, the program appears to have had a positive effect on patients’ use of health care services – while there was a significant decrease in the mean number of emergency room visits (n = 13 to n = 2; P = .0005), the results showed a favorable increase in mean number of follow-up visits with attendees’ primary care providers (n = 19 to n = 41; P = 3.47), physical therapists (n = 15 to n = 27; P = .004), or psychologists (n = 6 to n = 19; P = .003).
“The study was to evaluate the effect of the program after even just one appointment, and we found it really seemed to increase the use of more appropriate care, with less ER utilization and more visits to primary care,” Dr. Rensel said. The study even showed a small but significant reduction in pre- and postoutcome body mass index (BMI, 30.2 plus or minus 7.3 vs. 28.8 plus or minus 7.1; P = .03).
A critical metric that was not measured in the study – the effect of social interaction and camaraderie in a condition that can, for many, feel socially isolating – is clearly profound, Dr. Rensel said.
Amar Dhand, MD, associate professor of neurology at Brigham and Women’s Hospital, Harvard University, Boston, agreed that the peer support in such medical group settings can be highly valuable.
“Shared medical appointments offer an opportunity for peer-to-peer engagement, support, and education,” he said in an interview. “For many patients, this is a chance to bond with persons who are coexperiencing similar problems, allowing new social connections to emerge.”
Dr. Dhand, who spoke on the issue of the importance of social networks at the meeting, noted that, although there are numerous benefits with shared medical appointments, not all patients may respond well.
“Health care settings are one place to stimulate community among peers. This is one important ingredient of addressing social isolation,” he said. “However, there remain challenges such as sustainability of such relationships, paradoxical depression when persons see others with more severe disease, and infrastructure to support such programs.”
The findings from the study, however, do suggest favorable responses, he noted.
“I think, mechanistically, improved psychosocial outcomes are the most pertinent to the intervention,” Dr. Dhand said. “The health care utilization may be attributed to other factors and will need to be assessed in a case control design.”
Key benefits of the shared medical appointment concept
A recent article from Cleveland Clinic researchers reviewing the concept of shared medical appointments summarizes that the programs offer benefits based on nine key principles:
- Group exposure in shared medical appointments combats isolation, which in turn helps to remove doubts about one’s ability to manage illness.
- Patients learn about disease self-management vicariously by witnessing others’ illness experiences.
- Patients feel inspired by seeing others who are coping well.
- Group dynamics lead patients and providers to developing more equitable relationships.
- Providers feel increased appreciation and rapport toward colleagues leading to increased efficiency.
- Providers learn from the patients how better to meet their patients’ needs.
- Adequate time allotment of the SMA leads patients to feel supported.
- Patients receive professional expertise from the provider in combination with firsthand information from peers, resulting in more robust health knowledge.
- Patients have the opportunity to see how the physicians interact with fellow patients, which allows them to get to know the physician and better determine their level of trust.
The take-home message from the shared medical appointments concept is that “it may hit a quadruple aim,” Dr. Rensel said. “Access, cost, outcomes, and provider satisfaction.”
The Shared Medical Appointments program received a grant from Genzyme. Dr. Rensel reported consulting or advisory board relationships with Serono, Biogen, Teva, Genzyme, Novartis, and the National Multiple Sclerosis Society. Dr. Dhand had no disclosures to report.
REPORTING FROM ACTRIMS FORUM 2020
Incomplete MS relapse recovery predicted greater long-term disability
WEST PALM BEACH, FLA. – Failure to recover completely from early relapses in multiple sclerosis (MS) is significantly associated with higher long-term disability, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Incomplete recovery thus should be given more consideration when evaluating research and clinical practice outcomes, the study investigators cautioned.
“We found that the recovery from early relapses is an important predictor of future disability,” first author Marinos G. Sotiropoulos, MD, of the department of neurology, Brigham and Women’s Hospital, Boston, said in an interview. “It should be incorporated in future predictive models of disease severity and clinical trials, [and] it could be useful in clinical decision making as well.”
Incomplete recovery from relapses is known to be linked to disability progression and to the likelihood of transitioning to secondary progressive MS. Research on its role in longer-term outcomes is lacking, however.
To investigate the effect of incomplete relapse recovery in the first 3 years of MS on rates of disability at 10 years, Dr. Sotiropoulos and colleagues evaluated data on 360 patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation in Multiple Sclerosis at Brigham and Women’s Hospital) study. CLIMB is a natural history study spanning 20 years, with more than 2,000 patients.
Patients were included if at least 8.5 years had passed since their first documented symptom, if they were at least 18 years at their first visit to the Partners MS Center, if that visit occurred within 1 year of their first symptom, and if they had a diagnosis of relapsing-remitting MS or secondary progressive MS.
Among the 308 patients included in the study, 74% were female and 89% were white, with a mean age at the first symptom of 35.9 years.
A total of 403 early attacks from those 308 patients were included in the study. Half of the attacks (50.4%) were followed by incomplete recovery after 6 months, defined specifically as an increase in the Expanded Disability Status Scale (EDSS) scores from baseline to at least 6 months after the onset of the attack.
As of their 10-year visit, 27.3% of patients had a normal examination, defined as EDSS 0, and 64.1% had no significant disability (EDSS less than 2). The mean EDSS at 10 years was 1.52.
Patients’ recovery index, defined as the percentage of early attacks that recovered completely, was significantly associated with 10-year EDSS scores (P less than .001).
Patient age at first symptom was also a significant predictor of 10-year disability (P less than .004). Factors that were significantly associated with incomplete relapse recovery were the duration of time from first symptom (P less than .001) and moderate severity of the relapse (P = .029).
With the type of drug treatment likely representing an important factor in whether a patient has incomplete relapse recovery, the issue should be the subject of further research, Dr. Sotiropoulos said.
“This is something that is important to look at because none of the clinical trials for the drugs we currently have looked at relapse recovery as an outcome,” he explained.
“There have been some post hoc analyses [that] have shown that some of the new medications can improve recovery from relapses, but there is a lot to look into now that we know relapse recovery is an important clinical parameter,” he said. “We have to factor in the treatment effect in preventing residual disability after relapses.”
The findings suggest that “patients with incomplete early recovery might be considered for highly effective disease-modifying therapy,” added senior author Tanuja Chitnis, MD, also of the department of neurology at Brigham and Women’s Hospital. “We are now analyzing the biological mechanisms associated with relapse recovery.”
The authors of a recent study that echoes the importance of relapse recovery call it “the forgotten variable in multiple sclerosis clinical trials.” In that study, the researchers found an increased likelihood of a benign disease course among patients who received immediate disease-modifying therapy (DMT) initiation after failing to have a good recovery from an initial relapse (Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17;7[2]).
“Some clinicians may choose to hold off DMTs because the patient may not have high disease activity levels,” Burcu Zeydan, MD, a coauthor of that study and an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic, Rochester, Minn., said in an interview.
“What these studies add is that, if a patient is a poor recoverer despite not having highly active disease, that patient should be considered for immediate treatment initiation,” she said. “Otherwise, there is the possibility of a next relapse, which may not happen often. But when it happens, it may lead to more residual deficit with additional disability burden.”
The CLIMB study received funding from Mallinckrodt and the National MS Society Nancy Davis Center Without Walls. Dr. Sotiropoulos has received research support from Mallinckrodt. Dr. Chitnis has served on advisory boards for Biogen, Novartis, and Sanofi-Genzyme, and she has received research support from the Department of Defense, National MS Society, Guthy-Jackson Charitable Foundation, Novartis, Octave, Serono, and Verily. Dr. Zeydan had no disclosures to report.
SOURCE: Sotiropoulos MG et al. ACTRIMS Forum 2020. Abstract LB 317.
WEST PALM BEACH, FLA. – Failure to recover completely from early relapses in multiple sclerosis (MS) is significantly associated with higher long-term disability, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Incomplete recovery thus should be given more consideration when evaluating research and clinical practice outcomes, the study investigators cautioned.
“We found that the recovery from early relapses is an important predictor of future disability,” first author Marinos G. Sotiropoulos, MD, of the department of neurology, Brigham and Women’s Hospital, Boston, said in an interview. “It should be incorporated in future predictive models of disease severity and clinical trials, [and] it could be useful in clinical decision making as well.”
Incomplete recovery from relapses is known to be linked to disability progression and to the likelihood of transitioning to secondary progressive MS. Research on its role in longer-term outcomes is lacking, however.
To investigate the effect of incomplete relapse recovery in the first 3 years of MS on rates of disability at 10 years, Dr. Sotiropoulos and colleagues evaluated data on 360 patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation in Multiple Sclerosis at Brigham and Women’s Hospital) study. CLIMB is a natural history study spanning 20 years, with more than 2,000 patients.
Patients were included if at least 8.5 years had passed since their first documented symptom, if they were at least 18 years at their first visit to the Partners MS Center, if that visit occurred within 1 year of their first symptom, and if they had a diagnosis of relapsing-remitting MS or secondary progressive MS.
Among the 308 patients included in the study, 74% were female and 89% were white, with a mean age at the first symptom of 35.9 years.
A total of 403 early attacks from those 308 patients were included in the study. Half of the attacks (50.4%) were followed by incomplete recovery after 6 months, defined specifically as an increase in the Expanded Disability Status Scale (EDSS) scores from baseline to at least 6 months after the onset of the attack.
As of their 10-year visit, 27.3% of patients had a normal examination, defined as EDSS 0, and 64.1% had no significant disability (EDSS less than 2). The mean EDSS at 10 years was 1.52.
Patients’ recovery index, defined as the percentage of early attacks that recovered completely, was significantly associated with 10-year EDSS scores (P less than .001).
Patient age at first symptom was also a significant predictor of 10-year disability (P less than .004). Factors that were significantly associated with incomplete relapse recovery were the duration of time from first symptom (P less than .001) and moderate severity of the relapse (P = .029).
With the type of drug treatment likely representing an important factor in whether a patient has incomplete relapse recovery, the issue should be the subject of further research, Dr. Sotiropoulos said.
“This is something that is important to look at because none of the clinical trials for the drugs we currently have looked at relapse recovery as an outcome,” he explained.
“There have been some post hoc analyses [that] have shown that some of the new medications can improve recovery from relapses, but there is a lot to look into now that we know relapse recovery is an important clinical parameter,” he said. “We have to factor in the treatment effect in preventing residual disability after relapses.”
The findings suggest that “patients with incomplete early recovery might be considered for highly effective disease-modifying therapy,” added senior author Tanuja Chitnis, MD, also of the department of neurology at Brigham and Women’s Hospital. “We are now analyzing the biological mechanisms associated with relapse recovery.”
The authors of a recent study that echoes the importance of relapse recovery call it “the forgotten variable in multiple sclerosis clinical trials.” In that study, the researchers found an increased likelihood of a benign disease course among patients who received immediate disease-modifying therapy (DMT) initiation after failing to have a good recovery from an initial relapse (Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17;7[2]).
“Some clinicians may choose to hold off DMTs because the patient may not have high disease activity levels,” Burcu Zeydan, MD, a coauthor of that study and an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic, Rochester, Minn., said in an interview.
“What these studies add is that, if a patient is a poor recoverer despite not having highly active disease, that patient should be considered for immediate treatment initiation,” she said. “Otherwise, there is the possibility of a next relapse, which may not happen often. But when it happens, it may lead to more residual deficit with additional disability burden.”
The CLIMB study received funding from Mallinckrodt and the National MS Society Nancy Davis Center Without Walls. Dr. Sotiropoulos has received research support from Mallinckrodt. Dr. Chitnis has served on advisory boards for Biogen, Novartis, and Sanofi-Genzyme, and she has received research support from the Department of Defense, National MS Society, Guthy-Jackson Charitable Foundation, Novartis, Octave, Serono, and Verily. Dr. Zeydan had no disclosures to report.
SOURCE: Sotiropoulos MG et al. ACTRIMS Forum 2020. Abstract LB 317.
WEST PALM BEACH, FLA. – Failure to recover completely from early relapses in multiple sclerosis (MS) is significantly associated with higher long-term disability, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Incomplete recovery thus should be given more consideration when evaluating research and clinical practice outcomes, the study investigators cautioned.
“We found that the recovery from early relapses is an important predictor of future disability,” first author Marinos G. Sotiropoulos, MD, of the department of neurology, Brigham and Women’s Hospital, Boston, said in an interview. “It should be incorporated in future predictive models of disease severity and clinical trials, [and] it could be useful in clinical decision making as well.”
Incomplete recovery from relapses is known to be linked to disability progression and to the likelihood of transitioning to secondary progressive MS. Research on its role in longer-term outcomes is lacking, however.
To investigate the effect of incomplete relapse recovery in the first 3 years of MS on rates of disability at 10 years, Dr. Sotiropoulos and colleagues evaluated data on 360 patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation in Multiple Sclerosis at Brigham and Women’s Hospital) study. CLIMB is a natural history study spanning 20 years, with more than 2,000 patients.
Patients were included if at least 8.5 years had passed since their first documented symptom, if they were at least 18 years at their first visit to the Partners MS Center, if that visit occurred within 1 year of their first symptom, and if they had a diagnosis of relapsing-remitting MS or secondary progressive MS.
Among the 308 patients included in the study, 74% were female and 89% were white, with a mean age at the first symptom of 35.9 years.
A total of 403 early attacks from those 308 patients were included in the study. Half of the attacks (50.4%) were followed by incomplete recovery after 6 months, defined specifically as an increase in the Expanded Disability Status Scale (EDSS) scores from baseline to at least 6 months after the onset of the attack.
As of their 10-year visit, 27.3% of patients had a normal examination, defined as EDSS 0, and 64.1% had no significant disability (EDSS less than 2). The mean EDSS at 10 years was 1.52.
Patients’ recovery index, defined as the percentage of early attacks that recovered completely, was significantly associated with 10-year EDSS scores (P less than .001).
Patient age at first symptom was also a significant predictor of 10-year disability (P less than .004). Factors that were significantly associated with incomplete relapse recovery were the duration of time from first symptom (P less than .001) and moderate severity of the relapse (P = .029).
With the type of drug treatment likely representing an important factor in whether a patient has incomplete relapse recovery, the issue should be the subject of further research, Dr. Sotiropoulos said.
“This is something that is important to look at because none of the clinical trials for the drugs we currently have looked at relapse recovery as an outcome,” he explained.
“There have been some post hoc analyses [that] have shown that some of the new medications can improve recovery from relapses, but there is a lot to look into now that we know relapse recovery is an important clinical parameter,” he said. “We have to factor in the treatment effect in preventing residual disability after relapses.”
The findings suggest that “patients with incomplete early recovery might be considered for highly effective disease-modifying therapy,” added senior author Tanuja Chitnis, MD, also of the department of neurology at Brigham and Women’s Hospital. “We are now analyzing the biological mechanisms associated with relapse recovery.”
The authors of a recent study that echoes the importance of relapse recovery call it “the forgotten variable in multiple sclerosis clinical trials.” In that study, the researchers found an increased likelihood of a benign disease course among patients who received immediate disease-modifying therapy (DMT) initiation after failing to have a good recovery from an initial relapse (Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17;7[2]).
“Some clinicians may choose to hold off DMTs because the patient may not have high disease activity levels,” Burcu Zeydan, MD, a coauthor of that study and an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic, Rochester, Minn., said in an interview.
“What these studies add is that, if a patient is a poor recoverer despite not having highly active disease, that patient should be considered for immediate treatment initiation,” she said. “Otherwise, there is the possibility of a next relapse, which may not happen often. But when it happens, it may lead to more residual deficit with additional disability burden.”
The CLIMB study received funding from Mallinckrodt and the National MS Society Nancy Davis Center Without Walls. Dr. Sotiropoulos has received research support from Mallinckrodt. Dr. Chitnis has served on advisory boards for Biogen, Novartis, and Sanofi-Genzyme, and she has received research support from the Department of Defense, National MS Society, Guthy-Jackson Charitable Foundation, Novartis, Octave, Serono, and Verily. Dr. Zeydan had no disclosures to report.
SOURCE: Sotiropoulos MG et al. ACTRIMS Forum 2020. Abstract LB 317.
REPORTING FROM ACTRIMS FORUM 2020
Functional connectivity model identifies MS impairment
WEST PALM BEACH, FLA. – A machine learning model that combines data on the brain’s functional connectivity with clinical information such as age, sex and disease duration shows the potential to provide an accurate assessment of clinical impairment in patients with multiple sclerosis (MS).
“This is the first study to show that dynamic functional connectivity is useful to identify the impairment level in MS, and can be used for personalized treatment by clinicians,” first author Ceren Tozlu, PhD, of Weill Cornell Medicine, New York, said in an interview.
“We found out that structural connectivity is the most important feature that distinguishes MS patients from healthy controls, while dynamic functional connectivity was more discriminative compared to the static functional connectivity in MS patient classification regarding their impairment level.”
The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Statistical assessment of the clinical impairment of MS using MRI is hindered by a relatively weak correlation between the impairment and disease burden, such as lesion load.
However, the brain’s functional connectivity network, which is indicative of the disruption of the transmission of signals of gray matter regions, could provide a deeper understanding of connectome-level mechanisms that underlie variability in MS-related impairments, Dr. Tozlu and colleagues say.
With no previous study pulling together multimodal imaging data including static and dynamic functional connectivity to classify MS patients with a clinically significant impairment versus non–clinically significant impairment, Dr. Tozlu and the team sought to build a machine-learning–based model to do so.
For the study, they enrolled 79 patients with MS, including 42 with Expanded Disability Status scores of 2 or higher, representing clinically significant impairment at baseline.
The patients, who had a mean age of 45 years, were 66% female and had a mean disease duration of 12.48 years. The ensemble model that was used incorporated functional connectivity and a clinical dataset of age, sex, and disease duration. Functional connectivity was measured by evaluating blood oxygen level dependent (BOLD) signal activity between 86 FreeSurfer-based gray matter regions.
“Functional connectivity is a statistical correlation (Pearson’s correlation coefficient) between two time series of BOLD signals measured on two distinct region of interest of the brain during MRI scan,” Dr. Tozlu explained. “In our study, BOLD time series were measured using resting-state functional MRI technique that last 7 minutes.”
The ensemble model was able to classify low-adapting MS patients with an area under ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659. The model performed well in accurately classifying the MS patients with clinically significant impairment with a sensitivity of 0.719.
“The models in which we applied functional and structural connectivity showed a high performance in classifying MS patients regarding their impairment level,” Dr. Tozlu said.
She noted that “these models may be extended to predict change in impairment level in a longitudinal study, for instance, identifying MS patients who may have a clinically significant impairment.”
In further evaluating which particular functional connections were most related to MS disease activity, Dr. Tozlu and colleagues found the most discriminative areas were between the right superior parietal and right inferior temporal, between right lateral occipital and left pericalcarine, and between right pericalcarine and right side of frontal pole.
If further validated, the approach could have important, broader clinical implications, Dr. Tozlu said.
“If the validation of these models on a larger dataset is successful, this model may be used to decide for personalized treatment,” Dr. Tozlu added. “The model could offer guidance in providing more powerful treatment for MS patients who may have a clinically significant impairment and less powerful treatment for MS patients who may not have a clinically significant impairment in order to avoid the side effects of treatments.
“Therefore, we believe that dynamics in functional connectivity should be taken into account in the next studies in MS.”
In commenting on the research, Eric Klawiter, MD, associate professor of neurology, Harvard Medical School and associate neurologist at Massachusetts General Hospital, both in Boston, said the findings offer valuable insights in the use of machine learning and MS imaging.
“This research shows very nicely the power of machine learning and connectivity techniques to differentiate MS phenotypes based on disability level,” he said in an interview.
“The future direction of this work is to develop predictive markers for disability progression and this would have significant impact in how we evaluate newly diagnosed patients and counsel their treatment decisions.”
Dr. Tozlu and Dr. Klawiter had no disclosures to report.
SOURCE: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.
WEST PALM BEACH, FLA. – A machine learning model that combines data on the brain’s functional connectivity with clinical information such as age, sex and disease duration shows the potential to provide an accurate assessment of clinical impairment in patients with multiple sclerosis (MS).
“This is the first study to show that dynamic functional connectivity is useful to identify the impairment level in MS, and can be used for personalized treatment by clinicians,” first author Ceren Tozlu, PhD, of Weill Cornell Medicine, New York, said in an interview.
“We found out that structural connectivity is the most important feature that distinguishes MS patients from healthy controls, while dynamic functional connectivity was more discriminative compared to the static functional connectivity in MS patient classification regarding their impairment level.”
The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Statistical assessment of the clinical impairment of MS using MRI is hindered by a relatively weak correlation between the impairment and disease burden, such as lesion load.
However, the brain’s functional connectivity network, which is indicative of the disruption of the transmission of signals of gray matter regions, could provide a deeper understanding of connectome-level mechanisms that underlie variability in MS-related impairments, Dr. Tozlu and colleagues say.
With no previous study pulling together multimodal imaging data including static and dynamic functional connectivity to classify MS patients with a clinically significant impairment versus non–clinically significant impairment, Dr. Tozlu and the team sought to build a machine-learning–based model to do so.
For the study, they enrolled 79 patients with MS, including 42 with Expanded Disability Status scores of 2 or higher, representing clinically significant impairment at baseline.
The patients, who had a mean age of 45 years, were 66% female and had a mean disease duration of 12.48 years. The ensemble model that was used incorporated functional connectivity and a clinical dataset of age, sex, and disease duration. Functional connectivity was measured by evaluating blood oxygen level dependent (BOLD) signal activity between 86 FreeSurfer-based gray matter regions.
“Functional connectivity is a statistical correlation (Pearson’s correlation coefficient) between two time series of BOLD signals measured on two distinct region of interest of the brain during MRI scan,” Dr. Tozlu explained. “In our study, BOLD time series were measured using resting-state functional MRI technique that last 7 minutes.”
The ensemble model was able to classify low-adapting MS patients with an area under ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659. The model performed well in accurately classifying the MS patients with clinically significant impairment with a sensitivity of 0.719.
“The models in which we applied functional and structural connectivity showed a high performance in classifying MS patients regarding their impairment level,” Dr. Tozlu said.
She noted that “these models may be extended to predict change in impairment level in a longitudinal study, for instance, identifying MS patients who may have a clinically significant impairment.”
In further evaluating which particular functional connections were most related to MS disease activity, Dr. Tozlu and colleagues found the most discriminative areas were between the right superior parietal and right inferior temporal, between right lateral occipital and left pericalcarine, and between right pericalcarine and right side of frontal pole.
If further validated, the approach could have important, broader clinical implications, Dr. Tozlu said.
“If the validation of these models on a larger dataset is successful, this model may be used to decide for personalized treatment,” Dr. Tozlu added. “The model could offer guidance in providing more powerful treatment for MS patients who may have a clinically significant impairment and less powerful treatment for MS patients who may not have a clinically significant impairment in order to avoid the side effects of treatments.
“Therefore, we believe that dynamics in functional connectivity should be taken into account in the next studies in MS.”
In commenting on the research, Eric Klawiter, MD, associate professor of neurology, Harvard Medical School and associate neurologist at Massachusetts General Hospital, both in Boston, said the findings offer valuable insights in the use of machine learning and MS imaging.
“This research shows very nicely the power of machine learning and connectivity techniques to differentiate MS phenotypes based on disability level,” he said in an interview.
“The future direction of this work is to develop predictive markers for disability progression and this would have significant impact in how we evaluate newly diagnosed patients and counsel their treatment decisions.”
Dr. Tozlu and Dr. Klawiter had no disclosures to report.
SOURCE: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.
WEST PALM BEACH, FLA. – A machine learning model that combines data on the brain’s functional connectivity with clinical information such as age, sex and disease duration shows the potential to provide an accurate assessment of clinical impairment in patients with multiple sclerosis (MS).
“This is the first study to show that dynamic functional connectivity is useful to identify the impairment level in MS, and can be used for personalized treatment by clinicians,” first author Ceren Tozlu, PhD, of Weill Cornell Medicine, New York, said in an interview.
“We found out that structural connectivity is the most important feature that distinguishes MS patients from healthy controls, while dynamic functional connectivity was more discriminative compared to the static functional connectivity in MS patient classification regarding their impairment level.”
The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Statistical assessment of the clinical impairment of MS using MRI is hindered by a relatively weak correlation between the impairment and disease burden, such as lesion load.
However, the brain’s functional connectivity network, which is indicative of the disruption of the transmission of signals of gray matter regions, could provide a deeper understanding of connectome-level mechanisms that underlie variability in MS-related impairments, Dr. Tozlu and colleagues say.
With no previous study pulling together multimodal imaging data including static and dynamic functional connectivity to classify MS patients with a clinically significant impairment versus non–clinically significant impairment, Dr. Tozlu and the team sought to build a machine-learning–based model to do so.
For the study, they enrolled 79 patients with MS, including 42 with Expanded Disability Status scores of 2 or higher, representing clinically significant impairment at baseline.
The patients, who had a mean age of 45 years, were 66% female and had a mean disease duration of 12.48 years. The ensemble model that was used incorporated functional connectivity and a clinical dataset of age, sex, and disease duration. Functional connectivity was measured by evaluating blood oxygen level dependent (BOLD) signal activity between 86 FreeSurfer-based gray matter regions.
“Functional connectivity is a statistical correlation (Pearson’s correlation coefficient) between two time series of BOLD signals measured on two distinct region of interest of the brain during MRI scan,” Dr. Tozlu explained. “In our study, BOLD time series were measured using resting-state functional MRI technique that last 7 minutes.”
The ensemble model was able to classify low-adapting MS patients with an area under ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659. The model performed well in accurately classifying the MS patients with clinically significant impairment with a sensitivity of 0.719.
“The models in which we applied functional and structural connectivity showed a high performance in classifying MS patients regarding their impairment level,” Dr. Tozlu said.
She noted that “these models may be extended to predict change in impairment level in a longitudinal study, for instance, identifying MS patients who may have a clinically significant impairment.”
In further evaluating which particular functional connections were most related to MS disease activity, Dr. Tozlu and colleagues found the most discriminative areas were between the right superior parietal and right inferior temporal, between right lateral occipital and left pericalcarine, and between right pericalcarine and right side of frontal pole.
If further validated, the approach could have important, broader clinical implications, Dr. Tozlu said.
“If the validation of these models on a larger dataset is successful, this model may be used to decide for personalized treatment,” Dr. Tozlu added. “The model could offer guidance in providing more powerful treatment for MS patients who may have a clinically significant impairment and less powerful treatment for MS patients who may not have a clinically significant impairment in order to avoid the side effects of treatments.
“Therefore, we believe that dynamics in functional connectivity should be taken into account in the next studies in MS.”
In commenting on the research, Eric Klawiter, MD, associate professor of neurology, Harvard Medical School and associate neurologist at Massachusetts General Hospital, both in Boston, said the findings offer valuable insights in the use of machine learning and MS imaging.
“This research shows very nicely the power of machine learning and connectivity techniques to differentiate MS phenotypes based on disability level,” he said in an interview.
“The future direction of this work is to develop predictive markers for disability progression and this would have significant impact in how we evaluate newly diagnosed patients and counsel their treatment decisions.”
Dr. Tozlu and Dr. Klawiter had no disclosures to report.
SOURCE: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.
REPORTING FROM ACTRIMS FORUM 2020
Key clinical point:
Major finding: The model classified low-adapting MS patients with an ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659.
Study details: Modeling study based on 79 patients with MS, including low adapters.
Disclosures: Dr. Tozlu and Dr. Klawiter had no disclosures to report.
Source: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.
Cancer increase observed in modern era of MS drugs
WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”
With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.
“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.
In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.
The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).
Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”
“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”
However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.
Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.
And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”
“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.
WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”
With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.
“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.
In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.
The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).
Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”
“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”
However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.
Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.
And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”
“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.
WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”
With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.
“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.
In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.
The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).
Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”
“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”
However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.
Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.
And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”
“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.
REPORTING FROM ACTRIMS FORUM 2020
Pregnancy linked to slowed MS progression
The effect increases with multiple children
WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.
“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.
The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.
“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”
While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.
For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.
They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).
In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).
A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).
The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).
The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).
And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).
“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.
“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”
Early menopause also linked to shorter progression to secondary progressive MS
The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).
The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).
The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.
“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.
Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).
Possible mechanisms and applications of the findings
The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.
“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.
“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.
The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.
“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.
“However, our study ultimately may lead to such a trial.”
In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.
“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”
Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”
“More studies are needed in this important issue in a disease that affects women three times more than men.”
Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.
The effect increases with multiple children
The effect increases with multiple children
WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.
“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.
The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.
“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”
While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.
For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.
They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).
In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).
A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).
The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).
The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).
And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).
“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.
“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”
Early menopause also linked to shorter progression to secondary progressive MS
The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).
The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).
The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.
“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.
Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).
Possible mechanisms and applications of the findings
The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.
“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.
“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.
The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.
“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.
“However, our study ultimately may lead to such a trial.”
In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.
“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”
Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”
“More studies are needed in this important issue in a disease that affects women three times more than men.”
Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.
WEST PALM BEACH, FLA. – Women who have no history of a full-term pregnancy show an earlier onset of progressive multiple sclerosis (MS) compared to those who do have pregnancies, and the apparent onset-delaying effect appears to increase with the number of pregnancies, according to new research adding to speculation of the effects of pregnancy in MS.
“Our results suggest that a higher number of full-term pregnancies than average is associated with later onset of progressive MS, while having no full-term pregnancies is associated with significantly younger age at progressive MS onset,” first author Burcu Zeydan, MD, an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic in Rochester, Minn., said in an interview.
The study was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The findings, which also link early menopause with faster disease progression, offer important insights into the broader effects of pregnancy on MS, said ACTRIMS president Jeffrey A. Cohen, MD, director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
“We know pregnancy affects the short term disease activity – relapses tend to quiet down during pregnancy – but what has been somewhat conflicting is whether it affects the long-term prognosis or is just a temporary effect,” he said in an interview.
“So that is the main interest in this study, and it does indicate that pregnancy affects the long-term prognosis and provides some insight into the mechanism by which it might do that.”
While being female is in fact considered the most important risk factor for MS susceptibility, pregnancy has been suggested to have a protective role in disease progression, but more research is needed on the nature of the effect – and its mechanisms.
For the study, Dr. Zeydan and colleagues evaluated data on 202 patients with MS who were part of a Mayo Clinic survey, including 134 women and 68 men.
They found that women who had no full-term pregnancies (n = 32), had an earlier onset of progressive MS (mean age 41.4 ± 12.6 years) compared to women giving birth to 1 or more children (n = 95; 47.1 ± 9.7 years; P = .012).
In addition, the mean age of progressive MS onset also increased with a dose-effect trend according to number of full pregnancies (no children, 41.4 ± 12.6 years; 1-3 children: 46.4 ± 9.2 years; 4 or more children: 52.6 ± 12.9 years; P = .002).
A look at a subgroup of patients with secondary progressive MS also showed an earlier mean age of onset among women who had no full pregnancies (n = 19; 41.5 ± 9.2 years) compared to women with 1 or more full pregnancies (n = 57; 47.3 ± 10.6 years; P = .049).
The later disease onset associated with pregnancy was also seen in relapsing-remitting MS: Mean age of onset was earlier women with no pregnancies (27.5 ± 7.0 years) compared to those with one or more children (33.0 ± 9.4 years; P = .021).
The trends of later onset with more pregnancies was also observed with the mean age of onset of secondary progressive MS (no full pregnancies: onset at 41.5 ± 9.2 years; 1-3 pregnancies: 46.2 ± 9.9 years; 4 or more pregnancies, onset 52.6 ± 12.9 years; P = .010).
And likewise, the later mean age of onset of relapsing-remitting MS was seen with additional pregnancies (no full pregnancies: 27.5 ± 7.0 years; 1-3 pregnancies: 32.4 ± 9.3 years; 4 or more pregnancies: 35.8 ± 9.8 years; P = .012).
“The dose effect was clearly a surprise (having no full-term pregnancies vs. 1-3 vs. 4 or more),” Dr. Zeydan said.
“In addition to the significant difference between having no versus one or more full-term pregnancies, the clear dose-effect consolidates our results related to the association between the number of pregnancies and age at progressive MS onset.”
Early menopause also linked to shorter progression to secondary progressive MS
The study also showed that women with premature or early menopause had a shorter duration of progressing from relapsing-remitting MS to secondary progressive MS (n = 26; 12.9 ± 9.0 years) compared to women with normal age at menopause (n = 39; 17.8 ± 10.3 years).
The pattern was similar for women experiencing the onset of secondary progressive MS after menopause, with a shorter progression among those with early menopause (P = .012).
The patterns in early menopause are consistent with previous observations regarding menopause and MS progression, Dr. Cohen said.
“When women go through menopause, estradiol and pregnancy-related factors further decline and we know this coincides temporally with the development of progressive MS in women,” he noted.
Compared to men, women with premature or early menopause furthermore had a longer duration from relapsing-remitting MS to secondary progressive MS (P = .008), and women with secondary progressive MS also had also had an earlier age of relapsing-remitting MS onset than men (P = .018).
Possible mechanisms and applications of the findings
The mechanisms of pregnancy that could include a complex interaction between estrogen and factors such as astrocyte and microglia function, Dr. Zeydan explained.
“Estrogen, through various mechanisms of eliminating toxicity of highly activated neurons – including preventing proinflammatory molecule release, supporting mitochondria function thereby eliminating energy failure, and promoting remyelination – helps neuronal plasticity and delays neurodegeneration, which is closely related to the progressive phase of MS,” she said.
“One could easily make the probable association, while yet to be proven, that our findings may relate to these mechanisms,” Dr. Zeydan said.
The logical question of whether hormone replacement or some type of therapy that could mimic the effects of pregnancy could also benefit in delaying MS onset remained to be seen, Dr. Zeydan said.
“While we believe that is possible, particularly for delaying the onset of progressive phase, definitive evidence is lacking at this time,” Dr. Zeydan said.
“However, our study ultimately may lead to such a trial.”
In the meantime, the findings provide additional insights that may be beneficial in sharing with patients regarding pregnancy,” she said.
“As the contemporary problem in MS care is to delay or prevent progressive MS onset, our findings may suggest that how we counsel women with MS who are planning to get pregnant, or contemplating surgically induced menopause, or how we consider hormone therapies during perimenopause may impact the course of their disease.”
Dr. Zeydan cautioned, however, that “our findings do not confirm causality beyond an association.”
“More studies are needed in this important issue in a disease that affects women three times more than men.”
Dr. Zeydan had no disclosures to report. Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Zeydan B et al. ACTRIMS Forum 2020, Abstract P135.
REPORTING FROM ACTRIMS FORUM 2020
Radioactive iodine can be first-line for hyperthyroidism, says UK
New UK guidelines for the treatment of hyperthyroidism, including Graves’ disease, place heavier emphasis on the use of radioactive iodine as the frontline treatment for patients unlikely to remain remission-free on the medications, as opposed to the alternative of antithyroid medications as a first choice.
senior author Kristien Boelaert, MD, PhD, who led the guideline committee, said in an interview.
“Recommending the use of radioactive iodine as first-line treatment for adults with Graves’ disease is a change to current practice and should reduce the variation between centers as to when radioactive iodine is considered appropriate,” the guidelines further state.
The new recommendations on hyperthyroidism are part of broader guidelines on thyroid disease by the UK National Institute for Health and Care Excellence (NICE), which concludes that radioactive iodine results in cure in as many as 90% of hyperthyroidism cases.
The recommendations were published in a guideline summary in BMJ by research fellow Melina Vasileiou of the National Guideline Centre, Royal College of Physicians, London, and colleagues.
Current guidelines in the United Kingdom and Europe typically call for radioactive iodine to be reserved for use as a definitive treatment only after relapse following antithyroid medication treatment. The latest European Thyroid Association guidelines were published in 2018.
Elsewhere guidelines vary, with many, including those by the American Thyroid Association (ATA) – the most recent published in 2016 – generally calling for treatment with either antithyroid medications, radioactive iodine, or total thyroidectomy, in the absence of any contraindications to each treatment option.
“The U.S. tends to use more radioactive iodine, while Europe, Latin America, and Japan lean more toward (perhaps longer) use of antithyroid medications,” Angela Leung, MD, associate clinical professor of medicine in the division of endocrinology, diabetes, and metabolism, department of medicine, University of California, Los Angeles, said in an interview.
“Preferences of deciding which treatment option, which may involve more than one option if antithyroid medications are used initially, depend on a variety of factors related to patient desire, comorbidities, and availability of the therapy,” she explained.
Concerns including worsening thyroid eye disease, cardiovascular disease, and development of secondary cancers have caused some hesitation in the use of frontline radioiodine therapy.
And one notably controversial article, published last year, suggested a link between radioactive iodine therapy and an increased risk of cancer mortality. However, as reported by Medscape Medical News, the article spurred debate, with the Society for Endocrinology and British Thyroid Association issuing a joint statement urging caution in interpretation of the findings.
Evidence supporting first-line radioactive iodine
Patients treated with radioactive iodine take a single tablet that contains iodine and a low dose of radiation, which is absorbed by the thyroid. After taking the treatment patients are advised to avoid prolonged close contact with children and pregnant women for a few days or weeks and to avoid getting pregnant or fathering a child for several months. The treatment is likely to lead to an underactive thyroid gland that will require ongoing treatment with thyroid hormone replacement.
In providing evidence in favor of the benefits of radioactive iodine over the risks, the new NICE guidelines cite five randomized controlled trials of people with hyperthyroid disease, which, though defined as “low quality” evidence, collectively indicate that long-term outcomes were improved with radioactive iodine treatment compared with antithyroid drugs – despite the former having a higher risk of thyroid eye disease (also known as Graves’ ophthalmopathy).
In addition, eight nonrandomized studies show no evidence of a clinically important increase in cancer diagnoses or deaths between people treated with radioactive iodine or surgery, or between people treated with radioactive iodine and healthy controls, the guideline committee notes.
“The strongest arguments (in favor of radioactive iodine as a first-line therapy) were the likelihood of inducing remission of Graves’ disease with radioactive iodine, the finding that radioiodine is a safe treatment (confirmed in the safety review undertaken by NICE), and the reduction in the need for patients to remain on antithyroid drugs, which may have significant side effects and treatment which usually requires repeated hospital visits or follow-up under a hospital service,” said Dr. Boelaert.
The new guideline does recommend that antithyroid medication is acceptable as the first-line treatment among patients considered likely to achieve remission.
Dr. Leung explains that the percentage of patients with Graves’ disease who can achieve remission with antithyroid drugs ranges from 30% to 50%. She noted some evidence does suggest the long-term use of the drugs may be acceptable.
“There are some data that ... report the relative safety of long-term use of antithyroid drugs (beyond 24 months) for both Graves’ disease and autonomous thyroid nodules,” Dr. Leung elaborated.
Pregnancy concerns and cost-effectiveness of radioactive iodine
Radioactive iodine therapy is meanwhile not suitable if malignancy is suspected, if the patient is pregnant or trying to become pregnant, or if the patient has active thyroid eye disease, the experts agree.
Dr. Leung noted that although “it is generally advised to not treat Graves’ disease with radioiodine if there is concurrent thyroid eye disease, steroids are a proven effective therapy to decrease this risk in select patients.”
And among pregnant patients, “antithyroid medications should be minimally used in the lowest possible doses,” Dr. Leung said, although she added that, despite their potential risks, the drugs “represent a viable option” for this patient population.
“Also, many would actually advocate for total thyroidectomy in women who are thinking of pregnancy in the near future,” she noted.
Another factor of relevance in the guideline recommendations – cost – also favors radioactive iodine, the committee noted.
“Economic evidence showed that radioactive iodine was the most cost-effective intervention,” the committee pointed out.
Trabs advised for determination of hyperthyroidism cause
The new U.K. guidelines further underscore the importance of establishing the underlying cause of hyperthyroidism to ensure appropriate treatment, and the preferred method for doing so is the measurement of thyroid-stimulating hormone receptor antibodies (TRAbs).
“It is important to identify the underlying cause of thyrotoxicosis through measurement of TRAbs, or radioisotope scanning, in order to distinguish hyperthyroidism from transient causes of thyrotoxicosis such as transient thyroiditis, which only requires supportive treatment,” explained Dr. Boelaert, consultant endocrinologist and director of the National Institute for Health Research Integrated Academic Training Program at the Institute of Applied Health Research, University of Birmingham (England).
“In addition, this will help distinguish Graves’ disease from toxic nodular hyperthyroidism, which is important as antithyroid drugs are not effective in inducing a cure in the latter,” she explained.
Meanwhile, the new guidelines further note that although use of diagnostic ultrasound is informative when palpation suggests thyroid nodules, it is of limited diagnostic value for Graves’ disease.
“The recommendation (suggests that) thyroid ultrasonography should only be offered if there is a palpable thyroid nodule,” Dr. Boelaert noted.
She concluded: “There has been uncertainty in the U.K. about the best treatment for hyperthyroidism despite radioactive iodine being the most common first-line treatment for this condition in the United States. We are very pleased to have been able to work with NICE to provide clear new guidance which we hope will improve outcomes for patients with this condition.”
The National Guideline Centre was commissioned and funded by NICE to develop the guideline. No authors received specific funding to write the summary. Dr. Boelaert has reported no relevant financial relationships. Disclosures for the other authors are listed in the article.
This article first appeared on Medscape.com.
New UK guidelines for the treatment of hyperthyroidism, including Graves’ disease, place heavier emphasis on the use of radioactive iodine as the frontline treatment for patients unlikely to remain remission-free on the medications, as opposed to the alternative of antithyroid medications as a first choice.
senior author Kristien Boelaert, MD, PhD, who led the guideline committee, said in an interview.
“Recommending the use of radioactive iodine as first-line treatment for adults with Graves’ disease is a change to current practice and should reduce the variation between centers as to when radioactive iodine is considered appropriate,” the guidelines further state.
The new recommendations on hyperthyroidism are part of broader guidelines on thyroid disease by the UK National Institute for Health and Care Excellence (NICE), which concludes that radioactive iodine results in cure in as many as 90% of hyperthyroidism cases.
The recommendations were published in a guideline summary in BMJ by research fellow Melina Vasileiou of the National Guideline Centre, Royal College of Physicians, London, and colleagues.
Current guidelines in the United Kingdom and Europe typically call for radioactive iodine to be reserved for use as a definitive treatment only after relapse following antithyroid medication treatment. The latest European Thyroid Association guidelines were published in 2018.
Elsewhere guidelines vary, with many, including those by the American Thyroid Association (ATA) – the most recent published in 2016 – generally calling for treatment with either antithyroid medications, radioactive iodine, or total thyroidectomy, in the absence of any contraindications to each treatment option.
“The U.S. tends to use more radioactive iodine, while Europe, Latin America, and Japan lean more toward (perhaps longer) use of antithyroid medications,” Angela Leung, MD, associate clinical professor of medicine in the division of endocrinology, diabetes, and metabolism, department of medicine, University of California, Los Angeles, said in an interview.
“Preferences of deciding which treatment option, which may involve more than one option if antithyroid medications are used initially, depend on a variety of factors related to patient desire, comorbidities, and availability of the therapy,” she explained.
Concerns including worsening thyroid eye disease, cardiovascular disease, and development of secondary cancers have caused some hesitation in the use of frontline radioiodine therapy.
And one notably controversial article, published last year, suggested a link between radioactive iodine therapy and an increased risk of cancer mortality. However, as reported by Medscape Medical News, the article spurred debate, with the Society for Endocrinology and British Thyroid Association issuing a joint statement urging caution in interpretation of the findings.
Evidence supporting first-line radioactive iodine
Patients treated with radioactive iodine take a single tablet that contains iodine and a low dose of radiation, which is absorbed by the thyroid. After taking the treatment patients are advised to avoid prolonged close contact with children and pregnant women for a few days or weeks and to avoid getting pregnant or fathering a child for several months. The treatment is likely to lead to an underactive thyroid gland that will require ongoing treatment with thyroid hormone replacement.
In providing evidence in favor of the benefits of radioactive iodine over the risks, the new NICE guidelines cite five randomized controlled trials of people with hyperthyroid disease, which, though defined as “low quality” evidence, collectively indicate that long-term outcomes were improved with radioactive iodine treatment compared with antithyroid drugs – despite the former having a higher risk of thyroid eye disease (also known as Graves’ ophthalmopathy).
In addition, eight nonrandomized studies show no evidence of a clinically important increase in cancer diagnoses or deaths between people treated with radioactive iodine or surgery, or between people treated with radioactive iodine and healthy controls, the guideline committee notes.
“The strongest arguments (in favor of radioactive iodine as a first-line therapy) were the likelihood of inducing remission of Graves’ disease with radioactive iodine, the finding that radioiodine is a safe treatment (confirmed in the safety review undertaken by NICE), and the reduction in the need for patients to remain on antithyroid drugs, which may have significant side effects and treatment which usually requires repeated hospital visits or follow-up under a hospital service,” said Dr. Boelaert.
The new guideline does recommend that antithyroid medication is acceptable as the first-line treatment among patients considered likely to achieve remission.
Dr. Leung explains that the percentage of patients with Graves’ disease who can achieve remission with antithyroid drugs ranges from 30% to 50%. She noted some evidence does suggest the long-term use of the drugs may be acceptable.
“There are some data that ... report the relative safety of long-term use of antithyroid drugs (beyond 24 months) for both Graves’ disease and autonomous thyroid nodules,” Dr. Leung elaborated.
Pregnancy concerns and cost-effectiveness of radioactive iodine
Radioactive iodine therapy is meanwhile not suitable if malignancy is suspected, if the patient is pregnant or trying to become pregnant, or if the patient has active thyroid eye disease, the experts agree.
Dr. Leung noted that although “it is generally advised to not treat Graves’ disease with radioiodine if there is concurrent thyroid eye disease, steroids are a proven effective therapy to decrease this risk in select patients.”
And among pregnant patients, “antithyroid medications should be minimally used in the lowest possible doses,” Dr. Leung said, although she added that, despite their potential risks, the drugs “represent a viable option” for this patient population.
“Also, many would actually advocate for total thyroidectomy in women who are thinking of pregnancy in the near future,” she noted.
Another factor of relevance in the guideline recommendations – cost – also favors radioactive iodine, the committee noted.
“Economic evidence showed that radioactive iodine was the most cost-effective intervention,” the committee pointed out.
Trabs advised for determination of hyperthyroidism cause
The new U.K. guidelines further underscore the importance of establishing the underlying cause of hyperthyroidism to ensure appropriate treatment, and the preferred method for doing so is the measurement of thyroid-stimulating hormone receptor antibodies (TRAbs).
“It is important to identify the underlying cause of thyrotoxicosis through measurement of TRAbs, or radioisotope scanning, in order to distinguish hyperthyroidism from transient causes of thyrotoxicosis such as transient thyroiditis, which only requires supportive treatment,” explained Dr. Boelaert, consultant endocrinologist and director of the National Institute for Health Research Integrated Academic Training Program at the Institute of Applied Health Research, University of Birmingham (England).
“In addition, this will help distinguish Graves’ disease from toxic nodular hyperthyroidism, which is important as antithyroid drugs are not effective in inducing a cure in the latter,” she explained.
Meanwhile, the new guidelines further note that although use of diagnostic ultrasound is informative when palpation suggests thyroid nodules, it is of limited diagnostic value for Graves’ disease.
“The recommendation (suggests that) thyroid ultrasonography should only be offered if there is a palpable thyroid nodule,” Dr. Boelaert noted.
She concluded: “There has been uncertainty in the U.K. about the best treatment for hyperthyroidism despite radioactive iodine being the most common first-line treatment for this condition in the United States. We are very pleased to have been able to work with NICE to provide clear new guidance which we hope will improve outcomes for patients with this condition.”
The National Guideline Centre was commissioned and funded by NICE to develop the guideline. No authors received specific funding to write the summary. Dr. Boelaert has reported no relevant financial relationships. Disclosures for the other authors are listed in the article.
This article first appeared on Medscape.com.
New UK guidelines for the treatment of hyperthyroidism, including Graves’ disease, place heavier emphasis on the use of radioactive iodine as the frontline treatment for patients unlikely to remain remission-free on the medications, as opposed to the alternative of antithyroid medications as a first choice.
senior author Kristien Boelaert, MD, PhD, who led the guideline committee, said in an interview.
“Recommending the use of radioactive iodine as first-line treatment for adults with Graves’ disease is a change to current practice and should reduce the variation between centers as to when radioactive iodine is considered appropriate,” the guidelines further state.
The new recommendations on hyperthyroidism are part of broader guidelines on thyroid disease by the UK National Institute for Health and Care Excellence (NICE), which concludes that radioactive iodine results in cure in as many as 90% of hyperthyroidism cases.
The recommendations were published in a guideline summary in BMJ by research fellow Melina Vasileiou of the National Guideline Centre, Royal College of Physicians, London, and colleagues.
Current guidelines in the United Kingdom and Europe typically call for radioactive iodine to be reserved for use as a definitive treatment only after relapse following antithyroid medication treatment. The latest European Thyroid Association guidelines were published in 2018.
Elsewhere guidelines vary, with many, including those by the American Thyroid Association (ATA) – the most recent published in 2016 – generally calling for treatment with either antithyroid medications, radioactive iodine, or total thyroidectomy, in the absence of any contraindications to each treatment option.
“The U.S. tends to use more radioactive iodine, while Europe, Latin America, and Japan lean more toward (perhaps longer) use of antithyroid medications,” Angela Leung, MD, associate clinical professor of medicine in the division of endocrinology, diabetes, and metabolism, department of medicine, University of California, Los Angeles, said in an interview.
“Preferences of deciding which treatment option, which may involve more than one option if antithyroid medications are used initially, depend on a variety of factors related to patient desire, comorbidities, and availability of the therapy,” she explained.
Concerns including worsening thyroid eye disease, cardiovascular disease, and development of secondary cancers have caused some hesitation in the use of frontline radioiodine therapy.
And one notably controversial article, published last year, suggested a link between radioactive iodine therapy and an increased risk of cancer mortality. However, as reported by Medscape Medical News, the article spurred debate, with the Society for Endocrinology and British Thyroid Association issuing a joint statement urging caution in interpretation of the findings.
Evidence supporting first-line radioactive iodine
Patients treated with radioactive iodine take a single tablet that contains iodine and a low dose of radiation, which is absorbed by the thyroid. After taking the treatment patients are advised to avoid prolonged close contact with children and pregnant women for a few days or weeks and to avoid getting pregnant or fathering a child for several months. The treatment is likely to lead to an underactive thyroid gland that will require ongoing treatment with thyroid hormone replacement.
In providing evidence in favor of the benefits of radioactive iodine over the risks, the new NICE guidelines cite five randomized controlled trials of people with hyperthyroid disease, which, though defined as “low quality” evidence, collectively indicate that long-term outcomes were improved with radioactive iodine treatment compared with antithyroid drugs – despite the former having a higher risk of thyroid eye disease (also known as Graves’ ophthalmopathy).
In addition, eight nonrandomized studies show no evidence of a clinically important increase in cancer diagnoses or deaths between people treated with radioactive iodine or surgery, or between people treated with radioactive iodine and healthy controls, the guideline committee notes.
“The strongest arguments (in favor of radioactive iodine as a first-line therapy) were the likelihood of inducing remission of Graves’ disease with radioactive iodine, the finding that radioiodine is a safe treatment (confirmed in the safety review undertaken by NICE), and the reduction in the need for patients to remain on antithyroid drugs, which may have significant side effects and treatment which usually requires repeated hospital visits or follow-up under a hospital service,” said Dr. Boelaert.
The new guideline does recommend that antithyroid medication is acceptable as the first-line treatment among patients considered likely to achieve remission.
Dr. Leung explains that the percentage of patients with Graves’ disease who can achieve remission with antithyroid drugs ranges from 30% to 50%. She noted some evidence does suggest the long-term use of the drugs may be acceptable.
“There are some data that ... report the relative safety of long-term use of antithyroid drugs (beyond 24 months) for both Graves’ disease and autonomous thyroid nodules,” Dr. Leung elaborated.
Pregnancy concerns and cost-effectiveness of radioactive iodine
Radioactive iodine therapy is meanwhile not suitable if malignancy is suspected, if the patient is pregnant or trying to become pregnant, or if the patient has active thyroid eye disease, the experts agree.
Dr. Leung noted that although “it is generally advised to not treat Graves’ disease with radioiodine if there is concurrent thyroid eye disease, steroids are a proven effective therapy to decrease this risk in select patients.”
And among pregnant patients, “antithyroid medications should be minimally used in the lowest possible doses,” Dr. Leung said, although she added that, despite their potential risks, the drugs “represent a viable option” for this patient population.
“Also, many would actually advocate for total thyroidectomy in women who are thinking of pregnancy in the near future,” she noted.
Another factor of relevance in the guideline recommendations – cost – also favors radioactive iodine, the committee noted.
“Economic evidence showed that radioactive iodine was the most cost-effective intervention,” the committee pointed out.
Trabs advised for determination of hyperthyroidism cause
The new U.K. guidelines further underscore the importance of establishing the underlying cause of hyperthyroidism to ensure appropriate treatment, and the preferred method for doing so is the measurement of thyroid-stimulating hormone receptor antibodies (TRAbs).
“It is important to identify the underlying cause of thyrotoxicosis through measurement of TRAbs, or radioisotope scanning, in order to distinguish hyperthyroidism from transient causes of thyrotoxicosis such as transient thyroiditis, which only requires supportive treatment,” explained Dr. Boelaert, consultant endocrinologist and director of the National Institute for Health Research Integrated Academic Training Program at the Institute of Applied Health Research, University of Birmingham (England).
“In addition, this will help distinguish Graves’ disease from toxic nodular hyperthyroidism, which is important as antithyroid drugs are not effective in inducing a cure in the latter,” she explained.
Meanwhile, the new guidelines further note that although use of diagnostic ultrasound is informative when palpation suggests thyroid nodules, it is of limited diagnostic value for Graves’ disease.
“The recommendation (suggests that) thyroid ultrasonography should only be offered if there is a palpable thyroid nodule,” Dr. Boelaert noted.
She concluded: “There has been uncertainty in the U.K. about the best treatment for hyperthyroidism despite radioactive iodine being the most common first-line treatment for this condition in the United States. We are very pleased to have been able to work with NICE to provide clear new guidance which we hope will improve outcomes for patients with this condition.”
The National Guideline Centre was commissioned and funded by NICE to develop the guideline. No authors received specific funding to write the summary. Dr. Boelaert has reported no relevant financial relationships. Disclosures for the other authors are listed in the article.
This article first appeared on Medscape.com.
Postop Makeup Service Boosts Patient Satisfaction
ANAHEIM, CALIF. An in-office camouflage makeup expert can help mask postoperative bruising, swelling, or redness, which can make the difference to patients who feel injured or disfigured, said Howard Steinman, M.D., at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
It's not uncommon for dermatologists to simply give patients a list of a few paramedical products and send them on their way, without considering that most patients will not want to be seen in public, even by strangers, immediately after the procedure. "You may see a normal postop resultbruising, redness, or asymmetryand you think it looks like a normal, great result, but the patient probably doesn't see it that way," said Dr. Steinman, a dermatologist in private practice in Chula Vista, Calif.
The last thing a patient likely wants to do is go to a cosmetic counter with an unsightly face when the salespeople look like models, he added. "Having to buy the products outside the office is simply not a viable option for cosmetic patients."
The difficulties of using past-generation paramedical products turned many practitioners away from offering in-house camouflage makeup services.
But mineral makeup has changed all that. Newer products are much easier for staff people to use and for patients to learn to apply themselves. The products can be highly effective in normalizing or almost normalizing regular bruising, covering redness, and masking pigmentary changes.
The makeup helps cover expected discoloration caused by everything from ablative procedures, deeper peels, and S-lifts to blepharoplasty, Mohs surgery, and even botulinum type A injections.
The products are formulated for postsurgical use, are waterproof, have an SPF, and are easy to apply and remove, Dr. Steinman said. The paramedical products he uses include Youngblood Mineral Makeup, DermaColor Camouflage, and Lycogel. He said he does not have financial ties to any of the manufacturers.
There are some limitationsthe makeup usually won't cover three-dimensional conditions, for instance. And it often can't cover very dark bruising or a lack of texture, he noted.
The staff person in charge of applying the camouflage makeup can offer an added level of care and understanding that boosts patient satisfaction.
"If you use someone who's experienced in paramedical camouflage makeup, they understand the psyche of the postop patient, the procedures, and they have great credibility in your office." In Dr. Steinman's practice, the makeup expert is his wife, Diedre, but estheticians or other staff members with experience in paramedical camouflage makeup can take on the role.
To allow adequate time and planning for makeup application and training, the service is best offered as a postsurgical session, arranged along with the other procedures, Dr. Steinman recommended.
Makeup should be matched to patients' facial skin prior to laser or chemical peels to ensure the appropriate color will be available postoperatively, and patients should be told to bring in their own makeup to help them feel as "normal" as possible when they leave.
Considering the low cost and risk of camouflage makeup, the minimal office space required, and the high level of patient satisfaction, the inclusion of such services is very worthwhile, Dr. Steinman said.
"When this is incorporated in your office, the fear we all have of doing procedures that have downtime can be ameliorated," he said. "With something like CO2 laser resurfacing, for instance, I have no concerns about downtime."
"If you're not offering camouflage makeup, then you're missing the boat, because this really completes the whole package for the patient and makes you, the physician, feel much more secure," he added.
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
ANAHEIM, CALIF. An in-office camouflage makeup expert can help mask postoperative bruising, swelling, or redness, which can make the difference to patients who feel injured or disfigured, said Howard Steinman, M.D., at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
It's not uncommon for dermatologists to simply give patients a list of a few paramedical products and send them on their way, without considering that most patients will not want to be seen in public, even by strangers, immediately after the procedure. "You may see a normal postop resultbruising, redness, or asymmetryand you think it looks like a normal, great result, but the patient probably doesn't see it that way," said Dr. Steinman, a dermatologist in private practice in Chula Vista, Calif.
The last thing a patient likely wants to do is go to a cosmetic counter with an unsightly face when the salespeople look like models, he added. "Having to buy the products outside the office is simply not a viable option for cosmetic patients."
The difficulties of using past-generation paramedical products turned many practitioners away from offering in-house camouflage makeup services.
But mineral makeup has changed all that. Newer products are much easier for staff people to use and for patients to learn to apply themselves. The products can be highly effective in normalizing or almost normalizing regular bruising, covering redness, and masking pigmentary changes.
The makeup helps cover expected discoloration caused by everything from ablative procedures, deeper peels, and S-lifts to blepharoplasty, Mohs surgery, and even botulinum type A injections.
The products are formulated for postsurgical use, are waterproof, have an SPF, and are easy to apply and remove, Dr. Steinman said. The paramedical products he uses include Youngblood Mineral Makeup, DermaColor Camouflage, and Lycogel. He said he does not have financial ties to any of the manufacturers.
There are some limitationsthe makeup usually won't cover three-dimensional conditions, for instance. And it often can't cover very dark bruising or a lack of texture, he noted.
The staff person in charge of applying the camouflage makeup can offer an added level of care and understanding that boosts patient satisfaction.
"If you use someone who's experienced in paramedical camouflage makeup, they understand the psyche of the postop patient, the procedures, and they have great credibility in your office." In Dr. Steinman's practice, the makeup expert is his wife, Diedre, but estheticians or other staff members with experience in paramedical camouflage makeup can take on the role.
To allow adequate time and planning for makeup application and training, the service is best offered as a postsurgical session, arranged along with the other procedures, Dr. Steinman recommended.
Makeup should be matched to patients' facial skin prior to laser or chemical peels to ensure the appropriate color will be available postoperatively, and patients should be told to bring in their own makeup to help them feel as "normal" as possible when they leave.
Considering the low cost and risk of camouflage makeup, the minimal office space required, and the high level of patient satisfaction, the inclusion of such services is very worthwhile, Dr. Steinman said.
"When this is incorporated in your office, the fear we all have of doing procedures that have downtime can be ameliorated," he said. "With something like CO2 laser resurfacing, for instance, I have no concerns about downtime."
"If you're not offering camouflage makeup, then you're missing the boat, because this really completes the whole package for the patient and makes you, the physician, feel much more secure," he added.
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.
ANAHEIM, CALIF. An in-office camouflage makeup expert can help mask postoperative bruising, swelling, or redness, which can make the difference to patients who feel injured or disfigured, said Howard Steinman, M.D., at a cosmetic dermatology seminar sponsored by the Skin Disease Education Foundation.
It's not uncommon for dermatologists to simply give patients a list of a few paramedical products and send them on their way, without considering that most patients will not want to be seen in public, even by strangers, immediately after the procedure. "You may see a normal postop resultbruising, redness, or asymmetryand you think it looks like a normal, great result, but the patient probably doesn't see it that way," said Dr. Steinman, a dermatologist in private practice in Chula Vista, Calif.
The last thing a patient likely wants to do is go to a cosmetic counter with an unsightly face when the salespeople look like models, he added. "Having to buy the products outside the office is simply not a viable option for cosmetic patients."
The difficulties of using past-generation paramedical products turned many practitioners away from offering in-house camouflage makeup services.
But mineral makeup has changed all that. Newer products are much easier for staff people to use and for patients to learn to apply themselves. The products can be highly effective in normalizing or almost normalizing regular bruising, covering redness, and masking pigmentary changes.
The makeup helps cover expected discoloration caused by everything from ablative procedures, deeper peels, and S-lifts to blepharoplasty, Mohs surgery, and even botulinum type A injections.
The products are formulated for postsurgical use, are waterproof, have an SPF, and are easy to apply and remove, Dr. Steinman said. The paramedical products he uses include Youngblood Mineral Makeup, DermaColor Camouflage, and Lycogel. He said he does not have financial ties to any of the manufacturers.
There are some limitationsthe makeup usually won't cover three-dimensional conditions, for instance. And it often can't cover very dark bruising or a lack of texture, he noted.
The staff person in charge of applying the camouflage makeup can offer an added level of care and understanding that boosts patient satisfaction.
"If you use someone who's experienced in paramedical camouflage makeup, they understand the psyche of the postop patient, the procedures, and they have great credibility in your office." In Dr. Steinman's practice, the makeup expert is his wife, Diedre, but estheticians or other staff members with experience in paramedical camouflage makeup can take on the role.
To allow adequate time and planning for makeup application and training, the service is best offered as a postsurgical session, arranged along with the other procedures, Dr. Steinman recommended.
Makeup should be matched to patients' facial skin prior to laser or chemical peels to ensure the appropriate color will be available postoperatively, and patients should be told to bring in their own makeup to help them feel as "normal" as possible when they leave.
Considering the low cost and risk of camouflage makeup, the minimal office space required, and the high level of patient satisfaction, the inclusion of such services is very worthwhile, Dr. Steinman said.
"When this is incorporated in your office, the fear we all have of doing procedures that have downtime can be ameliorated," he said. "With something like CO2 laser resurfacing, for instance, I have no concerns about downtime."
"If you're not offering camouflage makeup, then you're missing the boat, because this really completes the whole package for the patient and makes you, the physician, feel much more secure," he added.
The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.