User login
Performance anxiety highly common among surgeons
a new study of surgeons in the United Kingdom shows.
“Performance anxiety or stage fright is a widely recognized problem in music and sports, and there are many similarities between these arenas and the operating theater,” first author Robert Miller, MRCS, of the Surgical Psychology and Performance Group and the department of plastic and reconstructive surgery at St. George’s Hospital NHS Trust, London, said in an interview. “We were aware of it anecdotally in a surgical context, but for one reason or another, perhaps professional pride and fear of negative perception, this is rarely openly discussed amongst surgeons.”
In the cross-sectional study, published in Annals of Surgery, Dr. Miller and colleagues surveyed surgeons in all specialties working in the United Kingdom who had at least 1 year of postgraduate surgical training.
Of a total of 631 responses received, 523 (83%) were included in the analysis. The median age of those who responded was 41.2 years, and the mean duration of surgical experience was 15.3 years (range, 1-52 years). Among them, 62% were men, and 52% were of consultant/attending grade.
All of the respondents – 100% – said they believed that performance anxiety affected surgeons, 87% reported having experienced it themselves, and 65% said they felt that performance anxiety had an effect on their surgical performance.
Both male and female surgeons who reported experiencing performance anxiety had significantly worse mental well-being, as assessed using the Short Warwick Edinburgh Mental Wellbeing Scale, compared with those who did not have performance anxiety (P < .0001 for men and P < .001 for women).
Overall, however, male surgeons had significantly better mental well-being, compared with female surgeons (P = .003), yet both genders had significantly lower mental well-being scores compared with U.K. population norms (P = .0019 for men and P = .0001 for women).
The gender differences are “clearly an important topic, which is likely multifactorial,” Dr. Miller told this news organization. “The gender well-being gap requires more in-depth research, and qualitative work involving female surgeons is critical.”
Surgical perfectionism was significantly more common among respondents who did have performance anxiety in comparison with those who did not (P < .0001).
“Although perfectionism may be a beneficial trait in surgery, our findings from hierarchical multiple regression analysis also indicate that perfectionism, [as well as] sex and experience, may drive surgical performance anxiety and help predict those experiencing [the anxiety],” the authors noted.
Performing in presence of colleagues a key trigger
By far, the leading trigger that was identified as prompting surgeon performance anxiety was the presence – and scrutiny – of colleagues within the parent specialty. This was reported by 151 respondents. Other triggers were having to perform on highly complex or high-risk cases (66 responses) and a lack of experience (30 responses).
Next to planning and preparation, opening up and talking about the anxiety and shedding light on the issue was seen as a leading strategy to help with the problem, but very few respondents reported openly sharing their struggles. Only 9% reported that they had shared it openly; 27% said they had confided in someone, and 47% did not respond to the question.
“I wish we talked about it more and shared our insecurities,” one respondent lamented. “Most of my colleagues pretend they are living gods.”
Only about 45% of respondents reported a specific technique for overcoming their anxiety. In addition to being open about the problem, other techniques included self-care, such as exercise; and distraction outside of work to get perspective; relaxation techniques such as deep or controlled breathing; music; mindfulness; and positive self-statements.
About 9% said they had received psychological counseling for performance anxiety, and only 3% reported using medication for the problem.
Anxiety a positive factor?
Surprisingly, 70% of respondents reported feeling that surgical performance anxiety could have a positive impact on surgical performance, which the authors noted is consistent with some theories.
“This may be explained by the traditional bell-curve relationship between arousal and performance, which describes a dose-dependent relationship between performance and arousal until a ‘tipping point,’ after which performance declines,” the authors explained. “A heightened awareness secondary to anxiety may be beneficial, but at high doses, anxiety can negatively affect attentional control and cause somatic symptoms.”
They noted that “the challenge would be to reap the benefits of low-level stimulation without incurring possible adverse effects.”
Dr. Miller said that, in determining whether selection bias had a role in the results, a detailed analysis showed that “our respondents were not skewed to those with only high levels of trait anxiety.
“We also had a good spread of consultants versus trainees [about half and half], and different specialties, so we feel this is likely to be a representative sample,” he told this news organization.
That being said, the results underscore the need for increased awareness – and open discussion – of the issue of surgical performance anxiety.
“Within other professions, particularly the performing arts and sports, performance psychology is becoming an integral part of training and development,” Dr. Miller said. “We feel surgeons should be supported in a similar manner.
“Surgical performance anxiety is normal for surgeons at all levels and not something to be ashamed about,” Dr. Miller added. “Talk about it, acknowledge it, and be supportive to your colleagues.”
Many keep it to themselves in ‘prevailing culture of stoicism’
Commenting on the study, Carter C. Lebares, MD, an associate professor of surgery and director of the Center for Mindfulness in Surgery, department of surgery, University of California, San Francisco, said she was not surprised to see the high rates of performance anxiety among surgeons.
“As surgeons, no matter how hard we train or how thoroughly we prepare our intellectual understanding or the patient, the disease process, and the operation, there may be surprises, unforeseen challenges, or off days,” Dr. Lebares said.
“And whatever we encounter, we are managing these things directly under the scrutiny of others – people who can affect our reputation, operating privileges, and mental health. So, I am not surprised this is a prevalent and widely recognized issue.”
Dr. Lebares noted that the reluctance to share the anxiety is part of a “challenging and recognized conundrum in both medicine and surgery and is a matter of the prevailing culture of stoicism.
“We often are called to shoulder tremendous weight intraoperatively (having perseverance, self-confidence, or sustained focus), and in owning the weight of complications (which eventually we all will have),” she said.
“So, we do need to be strong and not complain, [but] we also need to be able to set that aside [when appropriate] and ask for help or allow others to shoulder the weight for a while, and this is not [yet] a common part of surgical culture.”
Dr. Lebares added that randomized, controlled trials have shown benefits of mindfulness interventions on burnout and anxiety.
“We have observed positive effects on mental noise, self-perception, conflict resolution, and resilience in surgical residents trained in mindfulness-based cognitive skills,” she said. “[Residents] report applying these skills in the OR, in their home lives, and in how they approach their training/education.”
The authors disclosed no relevant financial relationships. Dr. Lebares has developed mindfulness-based cognitive skills training for surgeons but receives no financial compensation for the activities.
A version of this article first appeared on Medscape.com.
a new study of surgeons in the United Kingdom shows.
“Performance anxiety or stage fright is a widely recognized problem in music and sports, and there are many similarities between these arenas and the operating theater,” first author Robert Miller, MRCS, of the Surgical Psychology and Performance Group and the department of plastic and reconstructive surgery at St. George’s Hospital NHS Trust, London, said in an interview. “We were aware of it anecdotally in a surgical context, but for one reason or another, perhaps professional pride and fear of negative perception, this is rarely openly discussed amongst surgeons.”
In the cross-sectional study, published in Annals of Surgery, Dr. Miller and colleagues surveyed surgeons in all specialties working in the United Kingdom who had at least 1 year of postgraduate surgical training.
Of a total of 631 responses received, 523 (83%) were included in the analysis. The median age of those who responded was 41.2 years, and the mean duration of surgical experience was 15.3 years (range, 1-52 years). Among them, 62% were men, and 52% were of consultant/attending grade.
All of the respondents – 100% – said they believed that performance anxiety affected surgeons, 87% reported having experienced it themselves, and 65% said they felt that performance anxiety had an effect on their surgical performance.
Both male and female surgeons who reported experiencing performance anxiety had significantly worse mental well-being, as assessed using the Short Warwick Edinburgh Mental Wellbeing Scale, compared with those who did not have performance anxiety (P < .0001 for men and P < .001 for women).
Overall, however, male surgeons had significantly better mental well-being, compared with female surgeons (P = .003), yet both genders had significantly lower mental well-being scores compared with U.K. population norms (P = .0019 for men and P = .0001 for women).
The gender differences are “clearly an important topic, which is likely multifactorial,” Dr. Miller told this news organization. “The gender well-being gap requires more in-depth research, and qualitative work involving female surgeons is critical.”
Surgical perfectionism was significantly more common among respondents who did have performance anxiety in comparison with those who did not (P < .0001).
“Although perfectionism may be a beneficial trait in surgery, our findings from hierarchical multiple regression analysis also indicate that perfectionism, [as well as] sex and experience, may drive surgical performance anxiety and help predict those experiencing [the anxiety],” the authors noted.
Performing in presence of colleagues a key trigger
By far, the leading trigger that was identified as prompting surgeon performance anxiety was the presence – and scrutiny – of colleagues within the parent specialty. This was reported by 151 respondents. Other triggers were having to perform on highly complex or high-risk cases (66 responses) and a lack of experience (30 responses).
Next to planning and preparation, opening up and talking about the anxiety and shedding light on the issue was seen as a leading strategy to help with the problem, but very few respondents reported openly sharing their struggles. Only 9% reported that they had shared it openly; 27% said they had confided in someone, and 47% did not respond to the question.
“I wish we talked about it more and shared our insecurities,” one respondent lamented. “Most of my colleagues pretend they are living gods.”
Only about 45% of respondents reported a specific technique for overcoming their anxiety. In addition to being open about the problem, other techniques included self-care, such as exercise; and distraction outside of work to get perspective; relaxation techniques such as deep or controlled breathing; music; mindfulness; and positive self-statements.
About 9% said they had received psychological counseling for performance anxiety, and only 3% reported using medication for the problem.
Anxiety a positive factor?
Surprisingly, 70% of respondents reported feeling that surgical performance anxiety could have a positive impact on surgical performance, which the authors noted is consistent with some theories.
“This may be explained by the traditional bell-curve relationship between arousal and performance, which describes a dose-dependent relationship between performance and arousal until a ‘tipping point,’ after which performance declines,” the authors explained. “A heightened awareness secondary to anxiety may be beneficial, but at high doses, anxiety can negatively affect attentional control and cause somatic symptoms.”
They noted that “the challenge would be to reap the benefits of low-level stimulation without incurring possible adverse effects.”
Dr. Miller said that, in determining whether selection bias had a role in the results, a detailed analysis showed that “our respondents were not skewed to those with only high levels of trait anxiety.
“We also had a good spread of consultants versus trainees [about half and half], and different specialties, so we feel this is likely to be a representative sample,” he told this news organization.
That being said, the results underscore the need for increased awareness – and open discussion – of the issue of surgical performance anxiety.
“Within other professions, particularly the performing arts and sports, performance psychology is becoming an integral part of training and development,” Dr. Miller said. “We feel surgeons should be supported in a similar manner.
“Surgical performance anxiety is normal for surgeons at all levels and not something to be ashamed about,” Dr. Miller added. “Talk about it, acknowledge it, and be supportive to your colleagues.”
Many keep it to themselves in ‘prevailing culture of stoicism’
Commenting on the study, Carter C. Lebares, MD, an associate professor of surgery and director of the Center for Mindfulness in Surgery, department of surgery, University of California, San Francisco, said she was not surprised to see the high rates of performance anxiety among surgeons.
“As surgeons, no matter how hard we train or how thoroughly we prepare our intellectual understanding or the patient, the disease process, and the operation, there may be surprises, unforeseen challenges, or off days,” Dr. Lebares said.
“And whatever we encounter, we are managing these things directly under the scrutiny of others – people who can affect our reputation, operating privileges, and mental health. So, I am not surprised this is a prevalent and widely recognized issue.”
Dr. Lebares noted that the reluctance to share the anxiety is part of a “challenging and recognized conundrum in both medicine and surgery and is a matter of the prevailing culture of stoicism.
“We often are called to shoulder tremendous weight intraoperatively (having perseverance, self-confidence, or sustained focus), and in owning the weight of complications (which eventually we all will have),” she said.
“So, we do need to be strong and not complain, [but] we also need to be able to set that aside [when appropriate] and ask for help or allow others to shoulder the weight for a while, and this is not [yet] a common part of surgical culture.”
Dr. Lebares added that randomized, controlled trials have shown benefits of mindfulness interventions on burnout and anxiety.
“We have observed positive effects on mental noise, self-perception, conflict resolution, and resilience in surgical residents trained in mindfulness-based cognitive skills,” she said. “[Residents] report applying these skills in the OR, in their home lives, and in how they approach their training/education.”
The authors disclosed no relevant financial relationships. Dr. Lebares has developed mindfulness-based cognitive skills training for surgeons but receives no financial compensation for the activities.
A version of this article first appeared on Medscape.com.
a new study of surgeons in the United Kingdom shows.
“Performance anxiety or stage fright is a widely recognized problem in music and sports, and there are many similarities between these arenas and the operating theater,” first author Robert Miller, MRCS, of the Surgical Psychology and Performance Group and the department of plastic and reconstructive surgery at St. George’s Hospital NHS Trust, London, said in an interview. “We were aware of it anecdotally in a surgical context, but for one reason or another, perhaps professional pride and fear of negative perception, this is rarely openly discussed amongst surgeons.”
In the cross-sectional study, published in Annals of Surgery, Dr. Miller and colleagues surveyed surgeons in all specialties working in the United Kingdom who had at least 1 year of postgraduate surgical training.
Of a total of 631 responses received, 523 (83%) were included in the analysis. The median age of those who responded was 41.2 years, and the mean duration of surgical experience was 15.3 years (range, 1-52 years). Among them, 62% were men, and 52% were of consultant/attending grade.
All of the respondents – 100% – said they believed that performance anxiety affected surgeons, 87% reported having experienced it themselves, and 65% said they felt that performance anxiety had an effect on their surgical performance.
Both male and female surgeons who reported experiencing performance anxiety had significantly worse mental well-being, as assessed using the Short Warwick Edinburgh Mental Wellbeing Scale, compared with those who did not have performance anxiety (P < .0001 for men and P < .001 for women).
Overall, however, male surgeons had significantly better mental well-being, compared with female surgeons (P = .003), yet both genders had significantly lower mental well-being scores compared with U.K. population norms (P = .0019 for men and P = .0001 for women).
The gender differences are “clearly an important topic, which is likely multifactorial,” Dr. Miller told this news organization. “The gender well-being gap requires more in-depth research, and qualitative work involving female surgeons is critical.”
Surgical perfectionism was significantly more common among respondents who did have performance anxiety in comparison with those who did not (P < .0001).
“Although perfectionism may be a beneficial trait in surgery, our findings from hierarchical multiple regression analysis also indicate that perfectionism, [as well as] sex and experience, may drive surgical performance anxiety and help predict those experiencing [the anxiety],” the authors noted.
Performing in presence of colleagues a key trigger
By far, the leading trigger that was identified as prompting surgeon performance anxiety was the presence – and scrutiny – of colleagues within the parent specialty. This was reported by 151 respondents. Other triggers were having to perform on highly complex or high-risk cases (66 responses) and a lack of experience (30 responses).
Next to planning and preparation, opening up and talking about the anxiety and shedding light on the issue was seen as a leading strategy to help with the problem, but very few respondents reported openly sharing their struggles. Only 9% reported that they had shared it openly; 27% said they had confided in someone, and 47% did not respond to the question.
“I wish we talked about it more and shared our insecurities,” one respondent lamented. “Most of my colleagues pretend they are living gods.”
Only about 45% of respondents reported a specific technique for overcoming their anxiety. In addition to being open about the problem, other techniques included self-care, such as exercise; and distraction outside of work to get perspective; relaxation techniques such as deep or controlled breathing; music; mindfulness; and positive self-statements.
About 9% said they had received psychological counseling for performance anxiety, and only 3% reported using medication for the problem.
Anxiety a positive factor?
Surprisingly, 70% of respondents reported feeling that surgical performance anxiety could have a positive impact on surgical performance, which the authors noted is consistent with some theories.
“This may be explained by the traditional bell-curve relationship between arousal and performance, which describes a dose-dependent relationship between performance and arousal until a ‘tipping point,’ after which performance declines,” the authors explained. “A heightened awareness secondary to anxiety may be beneficial, but at high doses, anxiety can negatively affect attentional control and cause somatic symptoms.”
They noted that “the challenge would be to reap the benefits of low-level stimulation without incurring possible adverse effects.”
Dr. Miller said that, in determining whether selection bias had a role in the results, a detailed analysis showed that “our respondents were not skewed to those with only high levels of trait anxiety.
“We also had a good spread of consultants versus trainees [about half and half], and different specialties, so we feel this is likely to be a representative sample,” he told this news organization.
That being said, the results underscore the need for increased awareness – and open discussion – of the issue of surgical performance anxiety.
“Within other professions, particularly the performing arts and sports, performance psychology is becoming an integral part of training and development,” Dr. Miller said. “We feel surgeons should be supported in a similar manner.
“Surgical performance anxiety is normal for surgeons at all levels and not something to be ashamed about,” Dr. Miller added. “Talk about it, acknowledge it, and be supportive to your colleagues.”
Many keep it to themselves in ‘prevailing culture of stoicism’
Commenting on the study, Carter C. Lebares, MD, an associate professor of surgery and director of the Center for Mindfulness in Surgery, department of surgery, University of California, San Francisco, said she was not surprised to see the high rates of performance anxiety among surgeons.
“As surgeons, no matter how hard we train or how thoroughly we prepare our intellectual understanding or the patient, the disease process, and the operation, there may be surprises, unforeseen challenges, or off days,” Dr. Lebares said.
“And whatever we encounter, we are managing these things directly under the scrutiny of others – people who can affect our reputation, operating privileges, and mental health. So, I am not surprised this is a prevalent and widely recognized issue.”
Dr. Lebares noted that the reluctance to share the anxiety is part of a “challenging and recognized conundrum in both medicine and surgery and is a matter of the prevailing culture of stoicism.
“We often are called to shoulder tremendous weight intraoperatively (having perseverance, self-confidence, or sustained focus), and in owning the weight of complications (which eventually we all will have),” she said.
“So, we do need to be strong and not complain, [but] we also need to be able to set that aside [when appropriate] and ask for help or allow others to shoulder the weight for a while, and this is not [yet] a common part of surgical culture.”
Dr. Lebares added that randomized, controlled trials have shown benefits of mindfulness interventions on burnout and anxiety.
“We have observed positive effects on mental noise, self-perception, conflict resolution, and resilience in surgical residents trained in mindfulness-based cognitive skills,” she said. “[Residents] report applying these skills in the OR, in their home lives, and in how they approach their training/education.”
The authors disclosed no relevant financial relationships. Dr. Lebares has developed mindfulness-based cognitive skills training for surgeons but receives no financial compensation for the activities.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF SURGERY
Progressive muscle relaxation outperforms mindfulness in reducing grief severity
DENVER –
“Both progressive muscle relaxation and mindfulness training were shown to improve grief severity, yearning, depression symptoms, and stress, [but] the results from this study suggest that progressive muscle relaxation is most effective, compared to a wait-list control condition for improving grief,” study investigator Lindsey Knowles, PhD, senior fellow, MS Center of Excellence, Veterans Affairs Puget Sound Health Care System, and University of Washington, Seattle, told this news organization.
“With replication, progressive muscle relaxation could be a standalone intervention for nondisordered grief or a component of treatment for disordered grief,” Dr. Knowles said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Disordered grief
Approximately 10% of individuals grappling with loss “get stuck” in their grief and develop disordered grief, which is distinguished by repetitive thought processes of yearning and grief rumination, the investigators noted.
The researchers hypothesized that mindfulness training, which has been shown to reduce maladaptive repetitive thought, could be an effective intervention to prevent disordered grief.
To investigate, they enrolled 94 widows and widowers (mean age, 67.5 years) who were experiencing bereavement-related grief and were between 6 months and 4 years post loss.
The researchers compared a 6-week mindfulness intervention (n = 37) with a 6-week progressive muscle relaxation intervention (n = 35), Dr. Knowles said, because there has been speculation that benefits from mindfulness training may be related more to the relaxation response than to the actual mindfulness component.
Both study groups received the intervention in similar settings with matched instructors.
The mindfulness intervention sessions included 10-25 minutes of meditation and mindfulness practices. It also included instructions for home practice.
Participants in the progressive muscle relaxation group were trained to tense and relax the body’s various muscle groups with an end goal of learning to relax four key muscle groups without initial tensing.
A third group of patients were placed on a wait list with no intervention (n = 22).
Measures taken throughout the study interventions and at 1 month postintervention showed reductions in the study’s two primary outcomes of grief severity and yearning for both interventions versus baseline (P = < .003).
However, only the progressive muscle relaxation group had a significantly greater reduction in grief severity vs the wait-list control group (P = .020).
The muscle relaxation group also showed lower grief severity at 1month follow-up versus the wait-list group (P = .049) – with a value at that time falling below an established cutoff for complicated grief, based on the Revised Inventory of Complicated Grief.
All three treatment groups showed a drop in the third primary outcome of grief rumination (P < .001).
Secondary outcomes of depression and stress were reduced in both active study groups versus the wait-list group (P = .028). Sleep quality also improved in both active intervention groups.
Simple technique
Dr. Knowles said the study’s findings were unexpected.
“We had hypothesized that mindfulness training would outperform progressive muscle relaxation and wait-list for improving grief outcomes,” she said.
Mindfulness experts underscore that a state of global relaxation is considered integral to the benefits of mindfulness, which could explain the benefits of progressive muscle relaxation, Dr. Knowles noted.
Importantly, progressive muscle relaxation has a key advantage: It is quickly and easily learned, which may partially explain the study’s findings, she added.
“Progressive muscle relaxation is a relatively simple technique, so it is also likely that participants were able to master [the technique] over the 6-week intervention,” Dr. Knowles said. “On the other hand, the mindfulness intervention was an introduction to mindfulness, and mastery was not expected or likely over the 6-week intervention.”
Either way, the results shed important light on a potentially beneficial grief intervention.
“Although mindfulness training and progressive muscle relaxation practices may both be perceived as relaxing, mastering progressive muscle relaxation may in fact enable people to maintain better focus in the present moment and generalize nonreactive awareness to both positively and negatively balanced phenomena,” Dr. Knowles said.
However, “more research is necessary to clarify how progressive muscle relaxation improves grief outcomes in widows and widowers.”
CNS benefits?
Zoe Donaldson, PhD, assistant professor in behavioral neuroscience, department of psychology and neuroscience, University of Colorado, Boulder, said the study is important for ongoing efforts in finding effective therapies for grief.
“We often struggle to try to help those experiencing the pain of loss and this study suggests a discrete set of exercises that may help,” said Dr. Donaldson, who was not involved with the research.
She also described the study results as surprising, and speculated that a combination of factors could explain the findings.
“First, mindfulness is hard to achieve, so the moderate beneficial effects might increase with more substantial mindfulness training. Secondly, it is not clear why progressive muscle relaxation had an effect, but the focus and attention to detail may engage the central nervous system in a beneficial way that we don’t fully understand,” Dr. Donaldson said.
Importantly, it’s key to remember that grief is an individual condition when investigating therapies, Dr. Donaldson noted.
“We likely need to develop multiple interventions to help those who are grieving. Incorporating loss can take many forms,” she said.
The investigators and Dr. Donaldson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
“Both progressive muscle relaxation and mindfulness training were shown to improve grief severity, yearning, depression symptoms, and stress, [but] the results from this study suggest that progressive muscle relaxation is most effective, compared to a wait-list control condition for improving grief,” study investigator Lindsey Knowles, PhD, senior fellow, MS Center of Excellence, Veterans Affairs Puget Sound Health Care System, and University of Washington, Seattle, told this news organization.
“With replication, progressive muscle relaxation could be a standalone intervention for nondisordered grief or a component of treatment for disordered grief,” Dr. Knowles said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Disordered grief
Approximately 10% of individuals grappling with loss “get stuck” in their grief and develop disordered grief, which is distinguished by repetitive thought processes of yearning and grief rumination, the investigators noted.
The researchers hypothesized that mindfulness training, which has been shown to reduce maladaptive repetitive thought, could be an effective intervention to prevent disordered grief.
To investigate, they enrolled 94 widows and widowers (mean age, 67.5 years) who were experiencing bereavement-related grief and were between 6 months and 4 years post loss.
The researchers compared a 6-week mindfulness intervention (n = 37) with a 6-week progressive muscle relaxation intervention (n = 35), Dr. Knowles said, because there has been speculation that benefits from mindfulness training may be related more to the relaxation response than to the actual mindfulness component.
Both study groups received the intervention in similar settings with matched instructors.
The mindfulness intervention sessions included 10-25 minutes of meditation and mindfulness practices. It also included instructions for home practice.
Participants in the progressive muscle relaxation group were trained to tense and relax the body’s various muscle groups with an end goal of learning to relax four key muscle groups without initial tensing.
A third group of patients were placed on a wait list with no intervention (n = 22).
Measures taken throughout the study interventions and at 1 month postintervention showed reductions in the study’s two primary outcomes of grief severity and yearning for both interventions versus baseline (P = < .003).
However, only the progressive muscle relaxation group had a significantly greater reduction in grief severity vs the wait-list control group (P = .020).
The muscle relaxation group also showed lower grief severity at 1month follow-up versus the wait-list group (P = .049) – with a value at that time falling below an established cutoff for complicated grief, based on the Revised Inventory of Complicated Grief.
All three treatment groups showed a drop in the third primary outcome of grief rumination (P < .001).
Secondary outcomes of depression and stress were reduced in both active study groups versus the wait-list group (P = .028). Sleep quality also improved in both active intervention groups.
Simple technique
Dr. Knowles said the study’s findings were unexpected.
“We had hypothesized that mindfulness training would outperform progressive muscle relaxation and wait-list for improving grief outcomes,” she said.
Mindfulness experts underscore that a state of global relaxation is considered integral to the benefits of mindfulness, which could explain the benefits of progressive muscle relaxation, Dr. Knowles noted.
Importantly, progressive muscle relaxation has a key advantage: It is quickly and easily learned, which may partially explain the study’s findings, she added.
“Progressive muscle relaxation is a relatively simple technique, so it is also likely that participants were able to master [the technique] over the 6-week intervention,” Dr. Knowles said. “On the other hand, the mindfulness intervention was an introduction to mindfulness, and mastery was not expected or likely over the 6-week intervention.”
Either way, the results shed important light on a potentially beneficial grief intervention.
“Although mindfulness training and progressive muscle relaxation practices may both be perceived as relaxing, mastering progressive muscle relaxation may in fact enable people to maintain better focus in the present moment and generalize nonreactive awareness to both positively and negatively balanced phenomena,” Dr. Knowles said.
However, “more research is necessary to clarify how progressive muscle relaxation improves grief outcomes in widows and widowers.”
CNS benefits?
Zoe Donaldson, PhD, assistant professor in behavioral neuroscience, department of psychology and neuroscience, University of Colorado, Boulder, said the study is important for ongoing efforts in finding effective therapies for grief.
“We often struggle to try to help those experiencing the pain of loss and this study suggests a discrete set of exercises that may help,” said Dr. Donaldson, who was not involved with the research.
She also described the study results as surprising, and speculated that a combination of factors could explain the findings.
“First, mindfulness is hard to achieve, so the moderate beneficial effects might increase with more substantial mindfulness training. Secondly, it is not clear why progressive muscle relaxation had an effect, but the focus and attention to detail may engage the central nervous system in a beneficial way that we don’t fully understand,” Dr. Donaldson said.
Importantly, it’s key to remember that grief is an individual condition when investigating therapies, Dr. Donaldson noted.
“We likely need to develop multiple interventions to help those who are grieving. Incorporating loss can take many forms,” she said.
The investigators and Dr. Donaldson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
“Both progressive muscle relaxation and mindfulness training were shown to improve grief severity, yearning, depression symptoms, and stress, [but] the results from this study suggest that progressive muscle relaxation is most effective, compared to a wait-list control condition for improving grief,” study investigator Lindsey Knowles, PhD, senior fellow, MS Center of Excellence, Veterans Affairs Puget Sound Health Care System, and University of Washington, Seattle, told this news organization.
“With replication, progressive muscle relaxation could be a standalone intervention for nondisordered grief or a component of treatment for disordered grief,” Dr. Knowles said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Disordered grief
Approximately 10% of individuals grappling with loss “get stuck” in their grief and develop disordered grief, which is distinguished by repetitive thought processes of yearning and grief rumination, the investigators noted.
The researchers hypothesized that mindfulness training, which has been shown to reduce maladaptive repetitive thought, could be an effective intervention to prevent disordered grief.
To investigate, they enrolled 94 widows and widowers (mean age, 67.5 years) who were experiencing bereavement-related grief and were between 6 months and 4 years post loss.
The researchers compared a 6-week mindfulness intervention (n = 37) with a 6-week progressive muscle relaxation intervention (n = 35), Dr. Knowles said, because there has been speculation that benefits from mindfulness training may be related more to the relaxation response than to the actual mindfulness component.
Both study groups received the intervention in similar settings with matched instructors.
The mindfulness intervention sessions included 10-25 minutes of meditation and mindfulness practices. It also included instructions for home practice.
Participants in the progressive muscle relaxation group were trained to tense and relax the body’s various muscle groups with an end goal of learning to relax four key muscle groups without initial tensing.
A third group of patients were placed on a wait list with no intervention (n = 22).
Measures taken throughout the study interventions and at 1 month postintervention showed reductions in the study’s two primary outcomes of grief severity and yearning for both interventions versus baseline (P = < .003).
However, only the progressive muscle relaxation group had a significantly greater reduction in grief severity vs the wait-list control group (P = .020).
The muscle relaxation group also showed lower grief severity at 1month follow-up versus the wait-list group (P = .049) – with a value at that time falling below an established cutoff for complicated grief, based on the Revised Inventory of Complicated Grief.
All three treatment groups showed a drop in the third primary outcome of grief rumination (P < .001).
Secondary outcomes of depression and stress were reduced in both active study groups versus the wait-list group (P = .028). Sleep quality also improved in both active intervention groups.
Simple technique
Dr. Knowles said the study’s findings were unexpected.
“We had hypothesized that mindfulness training would outperform progressive muscle relaxation and wait-list for improving grief outcomes,” she said.
Mindfulness experts underscore that a state of global relaxation is considered integral to the benefits of mindfulness, which could explain the benefits of progressive muscle relaxation, Dr. Knowles noted.
Importantly, progressive muscle relaxation has a key advantage: It is quickly and easily learned, which may partially explain the study’s findings, she added.
“Progressive muscle relaxation is a relatively simple technique, so it is also likely that participants were able to master [the technique] over the 6-week intervention,” Dr. Knowles said. “On the other hand, the mindfulness intervention was an introduction to mindfulness, and mastery was not expected or likely over the 6-week intervention.”
Either way, the results shed important light on a potentially beneficial grief intervention.
“Although mindfulness training and progressive muscle relaxation practices may both be perceived as relaxing, mastering progressive muscle relaxation may in fact enable people to maintain better focus in the present moment and generalize nonreactive awareness to both positively and negatively balanced phenomena,” Dr. Knowles said.
However, “more research is necessary to clarify how progressive muscle relaxation improves grief outcomes in widows and widowers.”
CNS benefits?
Zoe Donaldson, PhD, assistant professor in behavioral neuroscience, department of psychology and neuroscience, University of Colorado, Boulder, said the study is important for ongoing efforts in finding effective therapies for grief.
“We often struggle to try to help those experiencing the pain of loss and this study suggests a discrete set of exercises that may help,” said Dr. Donaldson, who was not involved with the research.
She also described the study results as surprising, and speculated that a combination of factors could explain the findings.
“First, mindfulness is hard to achieve, so the moderate beneficial effects might increase with more substantial mindfulness training. Secondly, it is not clear why progressive muscle relaxation had an effect, but the focus and attention to detail may engage the central nervous system in a beneficial way that we don’t fully understand,” Dr. Donaldson said.
Importantly, it’s key to remember that grief is an individual condition when investigating therapies, Dr. Donaldson noted.
“We likely need to develop multiple interventions to help those who are grieving. Incorporating loss can take many forms,” she said.
The investigators and Dr. Donaldson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADAA 2022
High-intensity exercise helps patients with anxiety quit smoking
DENVER –
Results from a randomized study of 150 participants reporting symptoms of anxiety showed that among daily smokers who received a personalized, high-intensity aerobic intervention, rates of smoking abstinence were nearly twice as great as for those who received a lower-intensity exercise intervention.
“We are encouraged in the sense that we feel we have a targeted [smoking cessation] intervention to tailor to people with high anxiety sensitivity,” lead author Jasper A. Smits, PhD, professor at the Institute for Mental Health Research and the department of psychology, the University of Texas at Austin, told attendees during a presentation of the findings at the Anxiety and Depression Association of America (ADAA) 2022. The findings were recently published in Addiction.
Effective as CBT
Previous research shows that relatively short periods of exercise, lasting as little as 2 weeks, were associated with reductions in anxiety equivalent to 12 weeks of cognitive-behavioral therapy (CBT).
In light of these earlier findings, Dr. Smits and colleagues investigated the effect of an exercise intervention for smoking cessation based on the knowledge that individuals with anxiety disorders are more likely to smoke and less likely to succeed in quitting.
The initial study, which was published in 2016, included 136 smokers with high “anxiety sensitivity,” a heightened sensitivity to normal sensations associated with anxiety, potentially leading to panic attacks or other disorders.
Results showed that participation in the researchers’ Smoking Treatment Enhancement Program (STEP) was associated with significant improvements in prolonged smoking abstinence among those with high anxiety sensitivity but not those with low anxiety.
Building on these results, the new study evaluated the exercise program at a community level at four YMCA centers. This time all participants had high anxiety sensitivity, defined as a score of 23 or higher on the Anxiety Sensitivity Index–3.
The study included 150 adult participants who had high anxiety, were daily smokers, were motivated to quit smoking, and who reported that they did not currently participate in regular moderate exercise.
All participants (67.3% women; mean age, 38.6 years) took part in STEP, which included a 15-week exercise intervention with a personal trainer. Of the participants, 77 individuals were randomly assigned to receive high-intensity aerobic training that targeted 60%-85% of their heart rate reserve (HRR), while the other 73 were assigned to a lower-intensity control group in which training was only targeted to 20%-40% of their HRR.
All participants also received standard behavioral support with phone- or text-based CBT and nicotine replacement therapy (NRT).
The centers’ fitness instructors served as case managers who oversaw the smoking cessation exercise regimens of high-intensity versus low-intensity exercise. A broad array of aerobic exercise options were permitted, with the instructors working with participants to personalize their regimens.
“It’s important to take into consideration patients’ preferences [and] to work with the fitness instructors to find the right activity,” Dr. Smits said. He noted that options may include intense yoga or swimming. “So I think we just need to be creative in thinking about exercise as being more than just running,” he noted.
Abstinence rate doubled
The study’s primary endpoint was abstinence, defined as biologically verified 7-day point prevalence abstinence.
Results at 6-month follow-up showed that the primary endpoint was achieved by 27.6% of the higher-intensity intervention group, compared with just 14.8% of the lower-intensity group (odds ratio, 2.2; P = .005).
“It was encouraging to see we roughly doubled the abstinence rate at the 6-month follow-up,” Dr. Smits said. “Those receiving the high-intensity exercise intervention had greater abstinence rates spanning the entire study period versus the standard treatment.”
Of note, declines in anxiety sensitivity, as measured on the Reiss-Epstein-Gursky Anxiety Sensitivity Index, were observed in both groups. However, there was no significant difference in changes between the two groups.
Dr. Smits noted the investigators initially speculated that exercise would improve cessation success in individuals with anxiety sensitivity by providing exposure to the types of sensations that may trigger their anxiety, such as sweating and an accelerated heart rate, providing an opportunity for “extinction training” by desensitizing them to these experiences.
In addition, high-intensity exercise may also mitigate other anxiety symptoms, including panic disorder, pain, depression, overeating, and posttraumatic stress disorder, Dr. Smits said.
Real-world evidence
Commenting on the findings, Sahib S. Khalsa, MD, PhD, director of clinical operations at the Laureate Institute for Brain Research and associate professor at the University of Tulsa, Oklahoma, noted that the real-world nature of the study suggests its results are widely applicable.
It is also important to note that both the current and previous studies conducted by the investigators included NRT, “and thus the effects are more likely to be reflective of a grouping of therapies, something that is more reflective of current practice,” said Dr. Khalsa, who was not involved in the research.
He noted that initiating as well as maintaining exercise motivation over longer periods is challenging.
“The study likely addressed this challenge by using fitness instructors, which may be an important criterion for successful deployment of the intervention. We also don’t know whether maintaining an active exercise regimen is critical to maintaining smoking cessation,” Dr. Khalsa added.
Dr. Smits is a consultant for Big Health. Dr. Khalsa has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
Results from a randomized study of 150 participants reporting symptoms of anxiety showed that among daily smokers who received a personalized, high-intensity aerobic intervention, rates of smoking abstinence were nearly twice as great as for those who received a lower-intensity exercise intervention.
“We are encouraged in the sense that we feel we have a targeted [smoking cessation] intervention to tailor to people with high anxiety sensitivity,” lead author Jasper A. Smits, PhD, professor at the Institute for Mental Health Research and the department of psychology, the University of Texas at Austin, told attendees during a presentation of the findings at the Anxiety and Depression Association of America (ADAA) 2022. The findings were recently published in Addiction.
Effective as CBT
Previous research shows that relatively short periods of exercise, lasting as little as 2 weeks, were associated with reductions in anxiety equivalent to 12 weeks of cognitive-behavioral therapy (CBT).
In light of these earlier findings, Dr. Smits and colleagues investigated the effect of an exercise intervention for smoking cessation based on the knowledge that individuals with anxiety disorders are more likely to smoke and less likely to succeed in quitting.
The initial study, which was published in 2016, included 136 smokers with high “anxiety sensitivity,” a heightened sensitivity to normal sensations associated with anxiety, potentially leading to panic attacks or other disorders.
Results showed that participation in the researchers’ Smoking Treatment Enhancement Program (STEP) was associated with significant improvements in prolonged smoking abstinence among those with high anxiety sensitivity but not those with low anxiety.
Building on these results, the new study evaluated the exercise program at a community level at four YMCA centers. This time all participants had high anxiety sensitivity, defined as a score of 23 or higher on the Anxiety Sensitivity Index–3.
The study included 150 adult participants who had high anxiety, were daily smokers, were motivated to quit smoking, and who reported that they did not currently participate in regular moderate exercise.
All participants (67.3% women; mean age, 38.6 years) took part in STEP, which included a 15-week exercise intervention with a personal trainer. Of the participants, 77 individuals were randomly assigned to receive high-intensity aerobic training that targeted 60%-85% of their heart rate reserve (HRR), while the other 73 were assigned to a lower-intensity control group in which training was only targeted to 20%-40% of their HRR.
All participants also received standard behavioral support with phone- or text-based CBT and nicotine replacement therapy (NRT).
The centers’ fitness instructors served as case managers who oversaw the smoking cessation exercise regimens of high-intensity versus low-intensity exercise. A broad array of aerobic exercise options were permitted, with the instructors working with participants to personalize their regimens.
“It’s important to take into consideration patients’ preferences [and] to work with the fitness instructors to find the right activity,” Dr. Smits said. He noted that options may include intense yoga or swimming. “So I think we just need to be creative in thinking about exercise as being more than just running,” he noted.
Abstinence rate doubled
The study’s primary endpoint was abstinence, defined as biologically verified 7-day point prevalence abstinence.
Results at 6-month follow-up showed that the primary endpoint was achieved by 27.6% of the higher-intensity intervention group, compared with just 14.8% of the lower-intensity group (odds ratio, 2.2; P = .005).
“It was encouraging to see we roughly doubled the abstinence rate at the 6-month follow-up,” Dr. Smits said. “Those receiving the high-intensity exercise intervention had greater abstinence rates spanning the entire study period versus the standard treatment.”
Of note, declines in anxiety sensitivity, as measured on the Reiss-Epstein-Gursky Anxiety Sensitivity Index, were observed in both groups. However, there was no significant difference in changes between the two groups.
Dr. Smits noted the investigators initially speculated that exercise would improve cessation success in individuals with anxiety sensitivity by providing exposure to the types of sensations that may trigger their anxiety, such as sweating and an accelerated heart rate, providing an opportunity for “extinction training” by desensitizing them to these experiences.
In addition, high-intensity exercise may also mitigate other anxiety symptoms, including panic disorder, pain, depression, overeating, and posttraumatic stress disorder, Dr. Smits said.
Real-world evidence
Commenting on the findings, Sahib S. Khalsa, MD, PhD, director of clinical operations at the Laureate Institute for Brain Research and associate professor at the University of Tulsa, Oklahoma, noted that the real-world nature of the study suggests its results are widely applicable.
It is also important to note that both the current and previous studies conducted by the investigators included NRT, “and thus the effects are more likely to be reflective of a grouping of therapies, something that is more reflective of current practice,” said Dr. Khalsa, who was not involved in the research.
He noted that initiating as well as maintaining exercise motivation over longer periods is challenging.
“The study likely addressed this challenge by using fitness instructors, which may be an important criterion for successful deployment of the intervention. We also don’t know whether maintaining an active exercise regimen is critical to maintaining smoking cessation,” Dr. Khalsa added.
Dr. Smits is a consultant for Big Health. Dr. Khalsa has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
Results from a randomized study of 150 participants reporting symptoms of anxiety showed that among daily smokers who received a personalized, high-intensity aerobic intervention, rates of smoking abstinence were nearly twice as great as for those who received a lower-intensity exercise intervention.
“We are encouraged in the sense that we feel we have a targeted [smoking cessation] intervention to tailor to people with high anxiety sensitivity,” lead author Jasper A. Smits, PhD, professor at the Institute for Mental Health Research and the department of psychology, the University of Texas at Austin, told attendees during a presentation of the findings at the Anxiety and Depression Association of America (ADAA) 2022. The findings were recently published in Addiction.
Effective as CBT
Previous research shows that relatively short periods of exercise, lasting as little as 2 weeks, were associated with reductions in anxiety equivalent to 12 weeks of cognitive-behavioral therapy (CBT).
In light of these earlier findings, Dr. Smits and colleagues investigated the effect of an exercise intervention for smoking cessation based on the knowledge that individuals with anxiety disorders are more likely to smoke and less likely to succeed in quitting.
The initial study, which was published in 2016, included 136 smokers with high “anxiety sensitivity,” a heightened sensitivity to normal sensations associated with anxiety, potentially leading to panic attacks or other disorders.
Results showed that participation in the researchers’ Smoking Treatment Enhancement Program (STEP) was associated with significant improvements in prolonged smoking abstinence among those with high anxiety sensitivity but not those with low anxiety.
Building on these results, the new study evaluated the exercise program at a community level at four YMCA centers. This time all participants had high anxiety sensitivity, defined as a score of 23 or higher on the Anxiety Sensitivity Index–3.
The study included 150 adult participants who had high anxiety, were daily smokers, were motivated to quit smoking, and who reported that they did not currently participate in regular moderate exercise.
All participants (67.3% women; mean age, 38.6 years) took part in STEP, which included a 15-week exercise intervention with a personal trainer. Of the participants, 77 individuals were randomly assigned to receive high-intensity aerobic training that targeted 60%-85% of their heart rate reserve (HRR), while the other 73 were assigned to a lower-intensity control group in which training was only targeted to 20%-40% of their HRR.
All participants also received standard behavioral support with phone- or text-based CBT and nicotine replacement therapy (NRT).
The centers’ fitness instructors served as case managers who oversaw the smoking cessation exercise regimens of high-intensity versus low-intensity exercise. A broad array of aerobic exercise options were permitted, with the instructors working with participants to personalize their regimens.
“It’s important to take into consideration patients’ preferences [and] to work with the fitness instructors to find the right activity,” Dr. Smits said. He noted that options may include intense yoga or swimming. “So I think we just need to be creative in thinking about exercise as being more than just running,” he noted.
Abstinence rate doubled
The study’s primary endpoint was abstinence, defined as biologically verified 7-day point prevalence abstinence.
Results at 6-month follow-up showed that the primary endpoint was achieved by 27.6% of the higher-intensity intervention group, compared with just 14.8% of the lower-intensity group (odds ratio, 2.2; P = .005).
“It was encouraging to see we roughly doubled the abstinence rate at the 6-month follow-up,” Dr. Smits said. “Those receiving the high-intensity exercise intervention had greater abstinence rates spanning the entire study period versus the standard treatment.”
Of note, declines in anxiety sensitivity, as measured on the Reiss-Epstein-Gursky Anxiety Sensitivity Index, were observed in both groups. However, there was no significant difference in changes between the two groups.
Dr. Smits noted the investigators initially speculated that exercise would improve cessation success in individuals with anxiety sensitivity by providing exposure to the types of sensations that may trigger their anxiety, such as sweating and an accelerated heart rate, providing an opportunity for “extinction training” by desensitizing them to these experiences.
In addition, high-intensity exercise may also mitigate other anxiety symptoms, including panic disorder, pain, depression, overeating, and posttraumatic stress disorder, Dr. Smits said.
Real-world evidence
Commenting on the findings, Sahib S. Khalsa, MD, PhD, director of clinical operations at the Laureate Institute for Brain Research and associate professor at the University of Tulsa, Oklahoma, noted that the real-world nature of the study suggests its results are widely applicable.
It is also important to note that both the current and previous studies conducted by the investigators included NRT, “and thus the effects are more likely to be reflective of a grouping of therapies, something that is more reflective of current practice,” said Dr. Khalsa, who was not involved in the research.
He noted that initiating as well as maintaining exercise motivation over longer periods is challenging.
“The study likely addressed this challenge by using fitness instructors, which may be an important criterion for successful deployment of the intervention. We also don’t know whether maintaining an active exercise regimen is critical to maintaining smoking cessation,” Dr. Khalsa added.
Dr. Smits is a consultant for Big Health. Dr. Khalsa has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ADAA 2022
‘Staggeringly high’ rates of psychiatric symptoms after COVID-19
DENVER – Neurocognitive and psychiatric symptoms of mental illness, including posttraumatic stress disorder, are alarmingly high among patients who have previously had COVID-19 – even among those who were not hospitalized with the virus, new research shows.
The findings are from an online survey of more than 800 respondents.
“Regardless of how long ago they had been infected with COVID-19, all respondents had persistent symptoms,” co-investigator Beth Patterson, MSc, adjunct clinical professor at McMaster University, MacAnxiety Research Centre, Hamilton, Ont., told this news organization.
“The take-home message for clinicians is to be aware that if you have patients who had COVID-19, it’s quite likely that they may also experience a psychiatric issue and that they may have reduced resilience and lower quality-of-life [issues],” Ms. Patterson said.
The survey results were presented here at the Anxiety and Depression Association of America (ADAA) Conference 2022.
100% report symptoms
The study included 827 respondents (81% women) to an online survey who had contracted COVID.
Using validated symptom severity scores, respondents were assessed for mental health and neurocognitive issues, as well as some physical and quality-of-life factors.
Remarkably, all participants (100%) reported having current, persistent symptoms of COVID. In addition, 88% (n = 729) reported persistent neurocognitive symptoms, even though only 15.5% reported they had been hospitalized for COVID.
Of those hospitalized, 28.9% were treated in the intensive care unit; 42.2% stayed in hospital for less than 1 week; and 13.3% remained hospitalized for at least 3 weeks.
Data were not available on how long it had been since the patients were diagnosed or hospitalized, but most participants (68%) said they had not returned to normal functioning since contracting COVID.
The most common persistent symptoms were fatigue (75.9%), brain fog (67.9%), difficulty concentrating (61%), and weakness (51.2%).
More than half of respondents reported neurocognitive symptoms, including poor memory (57.4%) and word-finding problems in processing information (46.9%). Only 11% reported no persistent neurocognitive symptoms.
A total of 41.7% of respondents reported anxiety using the Generalized Anxiety Disorder-7 (GAD-7) scale, and rates of depression were 61.4% as assessed with the Patient Health Questionnaire (PHQ-9).
Rates of probable posttraumatic stress disorder were 40.5% as assessed via the PTSD checklist (PCL-5).
Although it wasn’t possible to use diagnostic screens, the assessment scores suggest strikingly high rates of mental health disorders among the respondents, Ms. Patterson said.
“When we look at the mean scores on the validated scales, we see percentages of probable diagnoses that are staggeringly higher than you would find in the population,” she added.
Of note, about 44% of respondents reported having had mental health treatment in the past, and 33.7% were receiving current mental health treatment.
Although the study had no control group, the findings are consistent with larger studies that have had comparator groups, including research recently published in the BMJ.
Poor understanding of COVID’s fallout
In an editorial accompanying the BMJ study, Scott Weich, MD, Mental Health Research Unit, School of Health and Related Research, University of Sheffield, United Kingdom, emphasized the need to better understand the lingering mental health aspects of COVID-19 infection.
“Our attachment to syndromal phenotypes means that we have learned remarkably little about the causes of mental ill health – in this case psychopathology associated with a viral pandemic,” Dr. Weich writes.
Dr. Weich called for improved efforts to understanding long COVID, as well as the establishment of more effective responses to the mental health fallout from the pandemic.
Commenting on the current study, Dr. Weich elaborated on the challenges in disentangling the causes of mental health effects in illness.
“In terms of other viruses, etc., there is a long history of debate and pitched battles between those that attribute mental health effects to predominantly biological processes, [involving] immunological and other responses, and those who understand these responses are mediated by psychological and social processes,” he noted.
“The story of myalgic encephalomyelitis/chronic fatigue syndrome speaks volumes about these different positions, and how difficult it can be to find a middle ground,” he said.
“This has been going on for centuries and may never be fully resolved, at least until we have clearer and more definitive evidence of pathophysiology, though this seems incredibly elusive,” Dr. Weich said.
The authors and Dr. Weich have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER – Neurocognitive and psychiatric symptoms of mental illness, including posttraumatic stress disorder, are alarmingly high among patients who have previously had COVID-19 – even among those who were not hospitalized with the virus, new research shows.
The findings are from an online survey of more than 800 respondents.
“Regardless of how long ago they had been infected with COVID-19, all respondents had persistent symptoms,” co-investigator Beth Patterson, MSc, adjunct clinical professor at McMaster University, MacAnxiety Research Centre, Hamilton, Ont., told this news organization.
“The take-home message for clinicians is to be aware that if you have patients who had COVID-19, it’s quite likely that they may also experience a psychiatric issue and that they may have reduced resilience and lower quality-of-life [issues],” Ms. Patterson said.
The survey results were presented here at the Anxiety and Depression Association of America (ADAA) Conference 2022.
100% report symptoms
The study included 827 respondents (81% women) to an online survey who had contracted COVID.
Using validated symptom severity scores, respondents were assessed for mental health and neurocognitive issues, as well as some physical and quality-of-life factors.
Remarkably, all participants (100%) reported having current, persistent symptoms of COVID. In addition, 88% (n = 729) reported persistent neurocognitive symptoms, even though only 15.5% reported they had been hospitalized for COVID.
Of those hospitalized, 28.9% were treated in the intensive care unit; 42.2% stayed in hospital for less than 1 week; and 13.3% remained hospitalized for at least 3 weeks.
Data were not available on how long it had been since the patients were diagnosed or hospitalized, but most participants (68%) said they had not returned to normal functioning since contracting COVID.
The most common persistent symptoms were fatigue (75.9%), brain fog (67.9%), difficulty concentrating (61%), and weakness (51.2%).
More than half of respondents reported neurocognitive symptoms, including poor memory (57.4%) and word-finding problems in processing information (46.9%). Only 11% reported no persistent neurocognitive symptoms.
A total of 41.7% of respondents reported anxiety using the Generalized Anxiety Disorder-7 (GAD-7) scale, and rates of depression were 61.4% as assessed with the Patient Health Questionnaire (PHQ-9).
Rates of probable posttraumatic stress disorder were 40.5% as assessed via the PTSD checklist (PCL-5).
Although it wasn’t possible to use diagnostic screens, the assessment scores suggest strikingly high rates of mental health disorders among the respondents, Ms. Patterson said.
“When we look at the mean scores on the validated scales, we see percentages of probable diagnoses that are staggeringly higher than you would find in the population,” she added.
Of note, about 44% of respondents reported having had mental health treatment in the past, and 33.7% were receiving current mental health treatment.
Although the study had no control group, the findings are consistent with larger studies that have had comparator groups, including research recently published in the BMJ.
Poor understanding of COVID’s fallout
In an editorial accompanying the BMJ study, Scott Weich, MD, Mental Health Research Unit, School of Health and Related Research, University of Sheffield, United Kingdom, emphasized the need to better understand the lingering mental health aspects of COVID-19 infection.
“Our attachment to syndromal phenotypes means that we have learned remarkably little about the causes of mental ill health – in this case psychopathology associated with a viral pandemic,” Dr. Weich writes.
Dr. Weich called for improved efforts to understanding long COVID, as well as the establishment of more effective responses to the mental health fallout from the pandemic.
Commenting on the current study, Dr. Weich elaborated on the challenges in disentangling the causes of mental health effects in illness.
“In terms of other viruses, etc., there is a long history of debate and pitched battles between those that attribute mental health effects to predominantly biological processes, [involving] immunological and other responses, and those who understand these responses are mediated by psychological and social processes,” he noted.
“The story of myalgic encephalomyelitis/chronic fatigue syndrome speaks volumes about these different positions, and how difficult it can be to find a middle ground,” he said.
“This has been going on for centuries and may never be fully resolved, at least until we have clearer and more definitive evidence of pathophysiology, though this seems incredibly elusive,” Dr. Weich said.
The authors and Dr. Weich have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER – Neurocognitive and psychiatric symptoms of mental illness, including posttraumatic stress disorder, are alarmingly high among patients who have previously had COVID-19 – even among those who were not hospitalized with the virus, new research shows.
The findings are from an online survey of more than 800 respondents.
“Regardless of how long ago they had been infected with COVID-19, all respondents had persistent symptoms,” co-investigator Beth Patterson, MSc, adjunct clinical professor at McMaster University, MacAnxiety Research Centre, Hamilton, Ont., told this news organization.
“The take-home message for clinicians is to be aware that if you have patients who had COVID-19, it’s quite likely that they may also experience a psychiatric issue and that they may have reduced resilience and lower quality-of-life [issues],” Ms. Patterson said.
The survey results were presented here at the Anxiety and Depression Association of America (ADAA) Conference 2022.
100% report symptoms
The study included 827 respondents (81% women) to an online survey who had contracted COVID.
Using validated symptom severity scores, respondents were assessed for mental health and neurocognitive issues, as well as some physical and quality-of-life factors.
Remarkably, all participants (100%) reported having current, persistent symptoms of COVID. In addition, 88% (n = 729) reported persistent neurocognitive symptoms, even though only 15.5% reported they had been hospitalized for COVID.
Of those hospitalized, 28.9% were treated in the intensive care unit; 42.2% stayed in hospital for less than 1 week; and 13.3% remained hospitalized for at least 3 weeks.
Data were not available on how long it had been since the patients were diagnosed or hospitalized, but most participants (68%) said they had not returned to normal functioning since contracting COVID.
The most common persistent symptoms were fatigue (75.9%), brain fog (67.9%), difficulty concentrating (61%), and weakness (51.2%).
More than half of respondents reported neurocognitive symptoms, including poor memory (57.4%) and word-finding problems in processing information (46.9%). Only 11% reported no persistent neurocognitive symptoms.
A total of 41.7% of respondents reported anxiety using the Generalized Anxiety Disorder-7 (GAD-7) scale, and rates of depression were 61.4% as assessed with the Patient Health Questionnaire (PHQ-9).
Rates of probable posttraumatic stress disorder were 40.5% as assessed via the PTSD checklist (PCL-5).
Although it wasn’t possible to use diagnostic screens, the assessment scores suggest strikingly high rates of mental health disorders among the respondents, Ms. Patterson said.
“When we look at the mean scores on the validated scales, we see percentages of probable diagnoses that are staggeringly higher than you would find in the population,” she added.
Of note, about 44% of respondents reported having had mental health treatment in the past, and 33.7% were receiving current mental health treatment.
Although the study had no control group, the findings are consistent with larger studies that have had comparator groups, including research recently published in the BMJ.
Poor understanding of COVID’s fallout
In an editorial accompanying the BMJ study, Scott Weich, MD, Mental Health Research Unit, School of Health and Related Research, University of Sheffield, United Kingdom, emphasized the need to better understand the lingering mental health aspects of COVID-19 infection.
“Our attachment to syndromal phenotypes means that we have learned remarkably little about the causes of mental ill health – in this case psychopathology associated with a viral pandemic,” Dr. Weich writes.
Dr. Weich called for improved efforts to understanding long COVID, as well as the establishment of more effective responses to the mental health fallout from the pandemic.
Commenting on the current study, Dr. Weich elaborated on the challenges in disentangling the causes of mental health effects in illness.
“In terms of other viruses, etc., there is a long history of debate and pitched battles between those that attribute mental health effects to predominantly biological processes, [involving] immunological and other responses, and those who understand these responses are mediated by psychological and social processes,” he noted.
“The story of myalgic encephalomyelitis/chronic fatigue syndrome speaks volumes about these different positions, and how difficult it can be to find a middle ground,” he said.
“This has been going on for centuries and may never be fully resolved, at least until we have clearer and more definitive evidence of pathophysiology, though this seems incredibly elusive,” Dr. Weich said.
The authors and Dr. Weich have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADAA 2022
Executive-function deficits a new treatment target for PTSD?
DENVER –
“To our knowledge, this study is the first to show that executive-function deficits maintain PTSD symptoms following trauma exposure,” investigators noted in research presented at the Anxiety and Depression Association of America (ADAA) Anxiety & Depression conference.
The results are important in “developing precision medicine–based approaches for alleviating [posttraumatic stress] symptoms, and improving well-established PTSD treatments for those with relative deficits in executive function,” study investigator Joseph R. Bardeen, PhD, associate professor at Auburn (Ala.) University, told meeting attendees.
The findings were published in the Journal of Anxiety Disorders.
Cognitive impairment
In earlier research, deficits in EF were associated with an increased vulnerability for PTSD symptoms. However, less is known about the role of these deficits, which can impair higher-level cognitive ability, in sustaining PTSD symptoms.
To investigate, the authors conducted a longitudinal study that included 98 participants aged 18-65 years who had been identified via phone screening as experiencing clinically significant PTSD symptoms.
Participants completed self-report measures for PTSD symptoms, as well as measures for EF deficits at baseline and 6-month (n = 92) and 12-month (n = 91) follow-up sessions.
A path analysis showed a significant relationship between baseline PTSD symptoms and EF deficits at 6 months (P < .001). Baseline PTSD symptoms were associated with 12-month PTSD symptoms (P < .04).
EF deficits at 6 months were also associated with 12-month PTSD symptoms (P = .02).
Importantly, no associations were observed between baseline or 6-month PTSD symptoms and EF deficits at 12 months. However, EF deficits at 6 months drove the relationship between PTSD symptoms at baseline and at 1 year (indirect effect = .061).
“What this suggests is that executive-function deficits are a mechanism that maintains patients’ symptoms over the course of 1 year,” Dr. Bardeen said.
“And you don’t see the reverse,” he added. “You don’t see that PTSD symptoms at [6 months] mediate the relationship between [baseline] and 6 month executive-function deficits.”
Surprising finding
The findings suggest deficits in executive functioning have a stronger role in maintaining PTSD symptoms than these symptoms have in maintaining EF deficits, Dr. Bardeen told this news organization.
“I had originally hypothesized a bidirectional relationship in which PTSD symptoms influenced future executive-function deficits and executive-function deficits influenced future PTSD symptoms,” he said.
“So, it was a surprise that, when accounting for both variables in the same model, executive-function deficits predicted future PTSD symptoms, but PTSD symptoms did not significantly predict future EF deficits,” he added.
Dr. Bardeen noted this suggests that EF deficits “may be a particularly important maintenance factor.”
In addition, he recommended the use of neuropsychological assessments prior to treatment to identify individuals with EF deficits and distinguish those deficits from PTSD symptoms.
“There is certainly overlap between executive-function deficits and PTSD symptoms,” Dr. Bardeen said. “For example, several of the symptoms of PTSD, such as concentration difficulties, may be indicators of executive-function deficits.”
He noted assessments such as the Delis Kaplan Executive Function System, and Clinician Administered PTSD Scale for DSM-5, when used as part of a larger assessment battery, can help differentiate between the EF deficits and PTSD.
“This would take several hours to administer, but in cases in which serious cognitive impairment is suspected, a comprehensive assessment is the way to go,” Dr. Bardeen said.
The standard approaches of prolonged exposure therapy and cognitive processing therapy can be effective in patients without EF deficits, while some modifications may benefit those with these deficits, he added.
“For example, it’s important to provide a more directive and structured environment in which the practitioner repeats key points frequently, uses concrete language, simplifies worksheets, and provides written summaries and reminder cards,” he said.
Further findings
In additional research presented at the meeting, Elsa Mattson, a PhD student from Case Western Reserve University, Cleveland, and colleagues reported findings further distinguishing the role of EF in PTSD.
In that study of 149 patients with chronic PTSD, those with low performing working memory, but not high working memory, had higher pre- as well as posttreatment PTSD symptom severity and depressive symptoms.
“Clinicians should consider that impairments in executive function may play a role in reduced treatment response, potentially impairing a client’s ability to learn new information in treatment,” the investigators wrote.
“Understanding how executive function processes change over the course of treatment, particularly in relation to processing the trauma memories, is an important next step,” they added.
The first study was supported by a grant from the National Institute of Mental Health. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
“To our knowledge, this study is the first to show that executive-function deficits maintain PTSD symptoms following trauma exposure,” investigators noted in research presented at the Anxiety and Depression Association of America (ADAA) Anxiety & Depression conference.
The results are important in “developing precision medicine–based approaches for alleviating [posttraumatic stress] symptoms, and improving well-established PTSD treatments for those with relative deficits in executive function,” study investigator Joseph R. Bardeen, PhD, associate professor at Auburn (Ala.) University, told meeting attendees.
The findings were published in the Journal of Anxiety Disorders.
Cognitive impairment
In earlier research, deficits in EF were associated with an increased vulnerability for PTSD symptoms. However, less is known about the role of these deficits, which can impair higher-level cognitive ability, in sustaining PTSD symptoms.
To investigate, the authors conducted a longitudinal study that included 98 participants aged 18-65 years who had been identified via phone screening as experiencing clinically significant PTSD symptoms.
Participants completed self-report measures for PTSD symptoms, as well as measures for EF deficits at baseline and 6-month (n = 92) and 12-month (n = 91) follow-up sessions.
A path analysis showed a significant relationship between baseline PTSD symptoms and EF deficits at 6 months (P < .001). Baseline PTSD symptoms were associated with 12-month PTSD symptoms (P < .04).
EF deficits at 6 months were also associated with 12-month PTSD symptoms (P = .02).
Importantly, no associations were observed between baseline or 6-month PTSD symptoms and EF deficits at 12 months. However, EF deficits at 6 months drove the relationship between PTSD symptoms at baseline and at 1 year (indirect effect = .061).
“What this suggests is that executive-function deficits are a mechanism that maintains patients’ symptoms over the course of 1 year,” Dr. Bardeen said.
“And you don’t see the reverse,” he added. “You don’t see that PTSD symptoms at [6 months] mediate the relationship between [baseline] and 6 month executive-function deficits.”
Surprising finding
The findings suggest deficits in executive functioning have a stronger role in maintaining PTSD symptoms than these symptoms have in maintaining EF deficits, Dr. Bardeen told this news organization.
“I had originally hypothesized a bidirectional relationship in which PTSD symptoms influenced future executive-function deficits and executive-function deficits influenced future PTSD symptoms,” he said.
“So, it was a surprise that, when accounting for both variables in the same model, executive-function deficits predicted future PTSD symptoms, but PTSD symptoms did not significantly predict future EF deficits,” he added.
Dr. Bardeen noted this suggests that EF deficits “may be a particularly important maintenance factor.”
In addition, he recommended the use of neuropsychological assessments prior to treatment to identify individuals with EF deficits and distinguish those deficits from PTSD symptoms.
“There is certainly overlap between executive-function deficits and PTSD symptoms,” Dr. Bardeen said. “For example, several of the symptoms of PTSD, such as concentration difficulties, may be indicators of executive-function deficits.”
He noted assessments such as the Delis Kaplan Executive Function System, and Clinician Administered PTSD Scale for DSM-5, when used as part of a larger assessment battery, can help differentiate between the EF deficits and PTSD.
“This would take several hours to administer, but in cases in which serious cognitive impairment is suspected, a comprehensive assessment is the way to go,” Dr. Bardeen said.
The standard approaches of prolonged exposure therapy and cognitive processing therapy can be effective in patients without EF deficits, while some modifications may benefit those with these deficits, he added.
“For example, it’s important to provide a more directive and structured environment in which the practitioner repeats key points frequently, uses concrete language, simplifies worksheets, and provides written summaries and reminder cards,” he said.
Further findings
In additional research presented at the meeting, Elsa Mattson, a PhD student from Case Western Reserve University, Cleveland, and colleagues reported findings further distinguishing the role of EF in PTSD.
In that study of 149 patients with chronic PTSD, those with low performing working memory, but not high working memory, had higher pre- as well as posttreatment PTSD symptom severity and depressive symptoms.
“Clinicians should consider that impairments in executive function may play a role in reduced treatment response, potentially impairing a client’s ability to learn new information in treatment,” the investigators wrote.
“Understanding how executive function processes change over the course of treatment, particularly in relation to processing the trauma memories, is an important next step,” they added.
The first study was supported by a grant from the National Institute of Mental Health. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
“To our knowledge, this study is the first to show that executive-function deficits maintain PTSD symptoms following trauma exposure,” investigators noted in research presented at the Anxiety and Depression Association of America (ADAA) Anxiety & Depression conference.
The results are important in “developing precision medicine–based approaches for alleviating [posttraumatic stress] symptoms, and improving well-established PTSD treatments for those with relative deficits in executive function,” study investigator Joseph R. Bardeen, PhD, associate professor at Auburn (Ala.) University, told meeting attendees.
The findings were published in the Journal of Anxiety Disorders.
Cognitive impairment
In earlier research, deficits in EF were associated with an increased vulnerability for PTSD symptoms. However, less is known about the role of these deficits, which can impair higher-level cognitive ability, in sustaining PTSD symptoms.
To investigate, the authors conducted a longitudinal study that included 98 participants aged 18-65 years who had been identified via phone screening as experiencing clinically significant PTSD symptoms.
Participants completed self-report measures for PTSD symptoms, as well as measures for EF deficits at baseline and 6-month (n = 92) and 12-month (n = 91) follow-up sessions.
A path analysis showed a significant relationship between baseline PTSD symptoms and EF deficits at 6 months (P < .001). Baseline PTSD symptoms were associated with 12-month PTSD symptoms (P < .04).
EF deficits at 6 months were also associated with 12-month PTSD symptoms (P = .02).
Importantly, no associations were observed between baseline or 6-month PTSD symptoms and EF deficits at 12 months. However, EF deficits at 6 months drove the relationship between PTSD symptoms at baseline and at 1 year (indirect effect = .061).
“What this suggests is that executive-function deficits are a mechanism that maintains patients’ symptoms over the course of 1 year,” Dr. Bardeen said.
“And you don’t see the reverse,” he added. “You don’t see that PTSD symptoms at [6 months] mediate the relationship between [baseline] and 6 month executive-function deficits.”
Surprising finding
The findings suggest deficits in executive functioning have a stronger role in maintaining PTSD symptoms than these symptoms have in maintaining EF deficits, Dr. Bardeen told this news organization.
“I had originally hypothesized a bidirectional relationship in which PTSD symptoms influenced future executive-function deficits and executive-function deficits influenced future PTSD symptoms,” he said.
“So, it was a surprise that, when accounting for both variables in the same model, executive-function deficits predicted future PTSD symptoms, but PTSD symptoms did not significantly predict future EF deficits,” he added.
Dr. Bardeen noted this suggests that EF deficits “may be a particularly important maintenance factor.”
In addition, he recommended the use of neuropsychological assessments prior to treatment to identify individuals with EF deficits and distinguish those deficits from PTSD symptoms.
“There is certainly overlap between executive-function deficits and PTSD symptoms,” Dr. Bardeen said. “For example, several of the symptoms of PTSD, such as concentration difficulties, may be indicators of executive-function deficits.”
He noted assessments such as the Delis Kaplan Executive Function System, and Clinician Administered PTSD Scale for DSM-5, when used as part of a larger assessment battery, can help differentiate between the EF deficits and PTSD.
“This would take several hours to administer, but in cases in which serious cognitive impairment is suspected, a comprehensive assessment is the way to go,” Dr. Bardeen said.
The standard approaches of prolonged exposure therapy and cognitive processing therapy can be effective in patients without EF deficits, while some modifications may benefit those with these deficits, he added.
“For example, it’s important to provide a more directive and structured environment in which the practitioner repeats key points frequently, uses concrete language, simplifies worksheets, and provides written summaries and reminder cards,” he said.
Further findings
In additional research presented at the meeting, Elsa Mattson, a PhD student from Case Western Reserve University, Cleveland, and colleagues reported findings further distinguishing the role of EF in PTSD.
In that study of 149 patients with chronic PTSD, those with low performing working memory, but not high working memory, had higher pre- as well as posttreatment PTSD symptom severity and depressive symptoms.
“Clinicians should consider that impairments in executive function may play a role in reduced treatment response, potentially impairing a client’s ability to learn new information in treatment,” the investigators wrote.
“Understanding how executive function processes change over the course of treatment, particularly in relation to processing the trauma memories, is an important next step,” they added.
The first study was supported by a grant from the National Institute of Mental Health. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
REPORTING FROM ADAA 2022
Early MS biomarkers may improve prediction of long-term outcomes
WEST PALM BEACH, FL – , new research suggests.
The research shows that once standard clinical models can be incorporated into practice, the early measurement of these biomarkers will provide useful information in predicting who may be at risk of poorer outcomes, researcher Gauruv Bose, MD, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, told this news organization.
The findings were presented at annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Better together?
Although higher baseline sNfL levels in MS have previously been linked to greater brain atrophy and other long-term outcomes, and sGFAP changes are also associated with inflammation and damage through the disease course, less is known about longer-term effects of the two biomarker measures combined, Dr. Bose said.
“The value of using both sNfL and sGFAP in predictive models is of interest, since one correlates with neuroaxonal damage, while the other has correlated with astrocytic glial damage/cell turnover – potentially, though differently, reflecting inflammatory damage and neurodegeneration,” he added.
To investigate the relationship, the researchers evaluated patients with MS enrolled at the Brigham Multiple Sclerosis Center. All underwent neurologic examinations every 6 months, and MRI scans and blood samples were collected every year. Some had more than 20 years of follow-up.
The first study involved 144 patients (mean age, 37.4 years) from whom two samples of sNfL and sGFAP were collected within 3 years of MS onset.
The median baseline sNfL level was 10.7 pg/mL, and 50 patients (34.7%) already showed increases in sNfL at the 1-year follow-up. Their median sGFAP level at onset was 96 pg/mL, and 59 patients (41%) showed increases in sGFAP at the 1-year follow-up.
Results showed that higher baseline sNfL levels were significantly associated with increased risk for MS relapse at 10 years (hazard ratio, 1.34; P = .04), as well as with the development of new MRI lesions (HR, 1.35; P = .022).
Of the study group, 25 (17.4%) developed secondary progressive MS (SPMS) by the 10-year follow-up. For those prognostic assessments, the investigators compared utilization of a model using well-established clinical predictors of SPMS with and without the inclusion of sNfL and sGFAP.
The clinical model included key factors such as age, sex, body mass index, Extended Disability Status Scale (EDSS), timed 25-foot walk, and other measures.
The researchers found the clinical model alone predicted 10-year outcomes with an area under the receiver operating characteristic curve (AUC) of 0.75. However, with the addition of baseline sNfL and sGFAP measures, the AUC was improved to 0.79 (P = .0008).
Furthermore, the inclusion of additional follow-up sNfL and sGFAP measurements taken after baseline further improved the model’s AUC (0.82; P = .046).
The addition of the sNfL and sGFAP measures to the clinical models also improved the prediction of disability in MS at 10 years on EDSS (P = .068), as well as prediction of 10-year brain T2 lesion volume (P = .009) and brain parenchymal fraction (P = .04).
Relapse predictor?
In the second study, Dr. Bose and colleagues evaluated the role of the two serum measures in predicting relapse after disease-modifying therapy (DMT) discontinuation. That study included 42 patients who discontinued DMT treatment after having been disease-activity free for 2 years while on the drugs. They were compared with 36 patients who had similar characteristics and had continued DMT treatment.
All patients (mean age, 44.5 years) had a mean of 7.4 years since prior disease activity.
Increases in sNfL following DMT discontinuation, but not before, were associated with a significantly greater risk for clinical disease worsening at a mean follow-up of 7.5 years (HR, 9.4; P = .007). Change in sGFAP was associated with new MRI lesions (HR, 8.3; P = .039), compared with no changes.
“The crux of this study” was that patients with increased biomarker levels after stopping DMTs “were at a significantly higher risk for disease activity in the future compared to those whose biomarker levels remained stable,” Dr. Bose noted.
“We think this finding, if replicated in another cohort, has the potential to be included in guidelines regarding stopping DMT in patients with MS,” he added.
Clinically useful?
Jeffrey Cohen, MD, current president of ACTRIMS, said the first study supports mounting evidence on how sNfL and sGFAP at onset can predict future disease and have the potential to improve current predictive models.
“Combining clinical, MRI, and serum biomarkers into a single model works better than any of the three factors individually,” said Dr. Cohen, who is director of the Mellen Center for MS Treatment and Research and professor of neurology at the Cleveland Clinic.
“For the clinician, this information may help with treatment selection,” he added.
Dr. Cohen noted that the suggestion that the biomarkers could also be helpful in predicting relapse after discontinuation is of importance.
“Increasingly, we are considering this issue in the clinical setting,” he said. However, he also noted some caveats.
“Interpretation of the results of the study is not straightforward, illustrating the complexity of the issue,” Dr. Cohen said. “One issue is that the patients in the study were relatively young, with an average age of 45, which is not a group in which we typically would consider stopping therapy.”
Dr. Bose has received a postdoctoral fellowship grant from the Multiple Sclerosis Society of Canada. Dr. Cohen reports having received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; speaking for H3 Communications; and serving as an editor of the Multiple Sclerosis Journal.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FL – , new research suggests.
The research shows that once standard clinical models can be incorporated into practice, the early measurement of these biomarkers will provide useful information in predicting who may be at risk of poorer outcomes, researcher Gauruv Bose, MD, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, told this news organization.
The findings were presented at annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Better together?
Although higher baseline sNfL levels in MS have previously been linked to greater brain atrophy and other long-term outcomes, and sGFAP changes are also associated with inflammation and damage through the disease course, less is known about longer-term effects of the two biomarker measures combined, Dr. Bose said.
“The value of using both sNfL and sGFAP in predictive models is of interest, since one correlates with neuroaxonal damage, while the other has correlated with astrocytic glial damage/cell turnover – potentially, though differently, reflecting inflammatory damage and neurodegeneration,” he added.
To investigate the relationship, the researchers evaluated patients with MS enrolled at the Brigham Multiple Sclerosis Center. All underwent neurologic examinations every 6 months, and MRI scans and blood samples were collected every year. Some had more than 20 years of follow-up.
The first study involved 144 patients (mean age, 37.4 years) from whom two samples of sNfL and sGFAP were collected within 3 years of MS onset.
The median baseline sNfL level was 10.7 pg/mL, and 50 patients (34.7%) already showed increases in sNfL at the 1-year follow-up. Their median sGFAP level at onset was 96 pg/mL, and 59 patients (41%) showed increases in sGFAP at the 1-year follow-up.
Results showed that higher baseline sNfL levels were significantly associated with increased risk for MS relapse at 10 years (hazard ratio, 1.34; P = .04), as well as with the development of new MRI lesions (HR, 1.35; P = .022).
Of the study group, 25 (17.4%) developed secondary progressive MS (SPMS) by the 10-year follow-up. For those prognostic assessments, the investigators compared utilization of a model using well-established clinical predictors of SPMS with and without the inclusion of sNfL and sGFAP.
The clinical model included key factors such as age, sex, body mass index, Extended Disability Status Scale (EDSS), timed 25-foot walk, and other measures.
The researchers found the clinical model alone predicted 10-year outcomes with an area under the receiver operating characteristic curve (AUC) of 0.75. However, with the addition of baseline sNfL and sGFAP measures, the AUC was improved to 0.79 (P = .0008).
Furthermore, the inclusion of additional follow-up sNfL and sGFAP measurements taken after baseline further improved the model’s AUC (0.82; P = .046).
The addition of the sNfL and sGFAP measures to the clinical models also improved the prediction of disability in MS at 10 years on EDSS (P = .068), as well as prediction of 10-year brain T2 lesion volume (P = .009) and brain parenchymal fraction (P = .04).
Relapse predictor?
In the second study, Dr. Bose and colleagues evaluated the role of the two serum measures in predicting relapse after disease-modifying therapy (DMT) discontinuation. That study included 42 patients who discontinued DMT treatment after having been disease-activity free for 2 years while on the drugs. They were compared with 36 patients who had similar characteristics and had continued DMT treatment.
All patients (mean age, 44.5 years) had a mean of 7.4 years since prior disease activity.
Increases in sNfL following DMT discontinuation, but not before, were associated with a significantly greater risk for clinical disease worsening at a mean follow-up of 7.5 years (HR, 9.4; P = .007). Change in sGFAP was associated with new MRI lesions (HR, 8.3; P = .039), compared with no changes.
“The crux of this study” was that patients with increased biomarker levels after stopping DMTs “were at a significantly higher risk for disease activity in the future compared to those whose biomarker levels remained stable,” Dr. Bose noted.
“We think this finding, if replicated in another cohort, has the potential to be included in guidelines regarding stopping DMT in patients with MS,” he added.
Clinically useful?
Jeffrey Cohen, MD, current president of ACTRIMS, said the first study supports mounting evidence on how sNfL and sGFAP at onset can predict future disease and have the potential to improve current predictive models.
“Combining clinical, MRI, and serum biomarkers into a single model works better than any of the three factors individually,” said Dr. Cohen, who is director of the Mellen Center for MS Treatment and Research and professor of neurology at the Cleveland Clinic.
“For the clinician, this information may help with treatment selection,” he added.
Dr. Cohen noted that the suggestion that the biomarkers could also be helpful in predicting relapse after discontinuation is of importance.
“Increasingly, we are considering this issue in the clinical setting,” he said. However, he also noted some caveats.
“Interpretation of the results of the study is not straightforward, illustrating the complexity of the issue,” Dr. Cohen said. “One issue is that the patients in the study were relatively young, with an average age of 45, which is not a group in which we typically would consider stopping therapy.”
Dr. Bose has received a postdoctoral fellowship grant from the Multiple Sclerosis Society of Canada. Dr. Cohen reports having received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; speaking for H3 Communications; and serving as an editor of the Multiple Sclerosis Journal.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FL – , new research suggests.
The research shows that once standard clinical models can be incorporated into practice, the early measurement of these biomarkers will provide useful information in predicting who may be at risk of poorer outcomes, researcher Gauruv Bose, MD, Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, told this news organization.
The findings were presented at annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Better together?
Although higher baseline sNfL levels in MS have previously been linked to greater brain atrophy and other long-term outcomes, and sGFAP changes are also associated with inflammation and damage through the disease course, less is known about longer-term effects of the two biomarker measures combined, Dr. Bose said.
“The value of using both sNfL and sGFAP in predictive models is of interest, since one correlates with neuroaxonal damage, while the other has correlated with astrocytic glial damage/cell turnover – potentially, though differently, reflecting inflammatory damage and neurodegeneration,” he added.
To investigate the relationship, the researchers evaluated patients with MS enrolled at the Brigham Multiple Sclerosis Center. All underwent neurologic examinations every 6 months, and MRI scans and blood samples were collected every year. Some had more than 20 years of follow-up.
The first study involved 144 patients (mean age, 37.4 years) from whom two samples of sNfL and sGFAP were collected within 3 years of MS onset.
The median baseline sNfL level was 10.7 pg/mL, and 50 patients (34.7%) already showed increases in sNfL at the 1-year follow-up. Their median sGFAP level at onset was 96 pg/mL, and 59 patients (41%) showed increases in sGFAP at the 1-year follow-up.
Results showed that higher baseline sNfL levels were significantly associated with increased risk for MS relapse at 10 years (hazard ratio, 1.34; P = .04), as well as with the development of new MRI lesions (HR, 1.35; P = .022).
Of the study group, 25 (17.4%) developed secondary progressive MS (SPMS) by the 10-year follow-up. For those prognostic assessments, the investigators compared utilization of a model using well-established clinical predictors of SPMS with and without the inclusion of sNfL and sGFAP.
The clinical model included key factors such as age, sex, body mass index, Extended Disability Status Scale (EDSS), timed 25-foot walk, and other measures.
The researchers found the clinical model alone predicted 10-year outcomes with an area under the receiver operating characteristic curve (AUC) of 0.75. However, with the addition of baseline sNfL and sGFAP measures, the AUC was improved to 0.79 (P = .0008).
Furthermore, the inclusion of additional follow-up sNfL and sGFAP measurements taken after baseline further improved the model’s AUC (0.82; P = .046).
The addition of the sNfL and sGFAP measures to the clinical models also improved the prediction of disability in MS at 10 years on EDSS (P = .068), as well as prediction of 10-year brain T2 lesion volume (P = .009) and brain parenchymal fraction (P = .04).
Relapse predictor?
In the second study, Dr. Bose and colleagues evaluated the role of the two serum measures in predicting relapse after disease-modifying therapy (DMT) discontinuation. That study included 42 patients who discontinued DMT treatment after having been disease-activity free for 2 years while on the drugs. They were compared with 36 patients who had similar characteristics and had continued DMT treatment.
All patients (mean age, 44.5 years) had a mean of 7.4 years since prior disease activity.
Increases in sNfL following DMT discontinuation, but not before, were associated with a significantly greater risk for clinical disease worsening at a mean follow-up of 7.5 years (HR, 9.4; P = .007). Change in sGFAP was associated with new MRI lesions (HR, 8.3; P = .039), compared with no changes.
“The crux of this study” was that patients with increased biomarker levels after stopping DMTs “were at a significantly higher risk for disease activity in the future compared to those whose biomarker levels remained stable,” Dr. Bose noted.
“We think this finding, if replicated in another cohort, has the potential to be included in guidelines regarding stopping DMT in patients with MS,” he added.
Clinically useful?
Jeffrey Cohen, MD, current president of ACTRIMS, said the first study supports mounting evidence on how sNfL and sGFAP at onset can predict future disease and have the potential to improve current predictive models.
“Combining clinical, MRI, and serum biomarkers into a single model works better than any of the three factors individually,” said Dr. Cohen, who is director of the Mellen Center for MS Treatment and Research and professor of neurology at the Cleveland Clinic.
“For the clinician, this information may help with treatment selection,” he added.
Dr. Cohen noted that the suggestion that the biomarkers could also be helpful in predicting relapse after discontinuation is of importance.
“Increasingly, we are considering this issue in the clinical setting,” he said. However, he also noted some caveats.
“Interpretation of the results of the study is not straightforward, illustrating the complexity of the issue,” Dr. Cohen said. “One issue is that the patients in the study were relatively young, with an average age of 45, which is not a group in which we typically would consider stopping therapy.”
Dr. Bose has received a postdoctoral fellowship grant from the Multiple Sclerosis Society of Canada. Dr. Cohen reports having received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; speaking for H3 Communications; and serving as an editor of the Multiple Sclerosis Journal.
A version of this article first appeared on Medscape.com.
Reporting from ACTRIMS Forumn 2022
Study links air pollution to psoriasis flares
Exposure to air pollution – even short term – may play a role in triggering psoriasis flares, according to new research from Italy, which found a significant association between exposure to higher levels of air pollution prior to patients presenting for psoriasis flares at medical visits, compared with visits unrelated to flares.
“We found that higher concentration of different air pollutants was associated with psoriasis flares in patients living in an industrialized city of the Po Valley” in Verona, Italy, report the authors of the study, published in JAMA Dermatology.
The findings underscore the need for clinicians to “consider environmental/external triggers in patients with chronic inflammatory diseases experiencing flares,” first author Francesco Bellinato, MD, of the Section of Dermatology and Venereology, University of Verona, Italy, told this news organization.
He and his coauthors conducted a case-crossover and cross-sectional longitudinal study that involved a retrospective analysis of data in 957 patients in Verona with chronic plaque psoriasis, who were evaluated every 3-4 months at an outpatient dermatology clinic for a median of 2.7 years.
Over the study period, disease flares, defined as an increase in the Psoriasis Area and Severity Index (PASI) of 5 or more points from the previous visit, occurred in 369 patients (38.6%), consistent with known flare rates in psoriasis. Participants in the study (mean age, 61) had median PASI scores of 12 during visits for psoriatic flares compared with PASI scores of 1 during control (no flare) visits (P < .001).
Evaluations of mean concentrations of several air pollutants within 10 miles of the patients over 4,398 visits showed that concentrations were significantly higher in the 60 days prior to the psoriasis flare, compared with control visits that were not related to flares (P < .05), after adjusting for factors including seasonality (by trimester, to adjust for weather conditions and UV/sunlight exposure) and the type of systemic psoriasis treatments patients were receiving (conventional or biological).
Increases in air pollutant levels prior to flares were observed among the 35.8% of patients who had a flare of at least a 50% increase in the PASI score, as well among the 47.2% of patients who had at least a 100% increase in PASI, compared with control visits not involving flares. In addition, mean and area-under-the-curve concentrations of air pollutants were higher in the 60 days before the visits among those with PASI 5 or greater, compared with those with PASI scores below 5, the authors add.
Dr. Bellinato noted that the associations were not limited to any particular subgroup. “The associations with air pollution and flares were observed in the entire population,” he said in an interview.
Vehicle, industry emissions
The pollutants that were measured were those mainly associated with fossil fuel combustion from vehicle and industry emissions, including carbon monoxide, nitrogen dioxide, other nitrogen oxides, benzene, coarse particulate matter (2.5-10.0 μm in diameter) and fine particulate matter (less than 2.5 μm in diameter).
They note that the risk of having a PASI score of 5 or greater was elevated even at thresholds of exposure that are largely considered safe. “Indeed, the risk for having a PASI score of 5 or greater was 40% to 50% higher at exposures as low as 20 μg/m3” of coarse particulate matter and 15 μg/m3 of fine particulate matter in the 60-day period prior to the visits, they write.
The authors referred to evidence linking air pollution with a worsening of a variety of inflammatory cutaneous diseases, including atopic dermatitis and acne, as well as photoaging. Psoriasis flares are known to be triggered by a variety of environmental factors, including infections or certain drugs; however, evidence of a role of air pollution has been lacking. Potential mechanisms linking the exposures to flares include the possibility that exhaust particles can activate skin resident T-cells, “resulting in abnormal production of proinflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukins (ILs), including IL-1α, IL-1β, IL-6, and IL-8.8,” the authors write.
Their results, though inferring a causal relationship, fall short of showing a clear dose–response relationship between higher pollutant levels and an increased risk of psoriasis flares, possibly the result of a smaller sample size of subjects exposed to higher levels of pollution, they add.
Limitations of the study included the definition of flare, which used a clinical score that could be affected by other measurements, they point out, while strengths of the study included the large cohort of patients followed for over 7 years and the availability of daily measurements of air pollutants.
While the study suggests that environmental air pollutant fluctuations may affect psoriasis course,” the authors concluded, “further study is needed to examine whether these findings generalize to other populations and to better understand the mechanisms by which air pollution may affect psoriasis disease activity.”
Dr. Bellinato and four coauthors had no disclosures; the remaining authors had disclosures that included receiving personal fees from pharmaceutical companies that were outside of the submitted work.
A version of this article first appeared on Medscape.com.
Exposure to air pollution – even short term – may play a role in triggering psoriasis flares, according to new research from Italy, which found a significant association between exposure to higher levels of air pollution prior to patients presenting for psoriasis flares at medical visits, compared with visits unrelated to flares.
“We found that higher concentration of different air pollutants was associated with psoriasis flares in patients living in an industrialized city of the Po Valley” in Verona, Italy, report the authors of the study, published in JAMA Dermatology.
The findings underscore the need for clinicians to “consider environmental/external triggers in patients with chronic inflammatory diseases experiencing flares,” first author Francesco Bellinato, MD, of the Section of Dermatology and Venereology, University of Verona, Italy, told this news organization.
He and his coauthors conducted a case-crossover and cross-sectional longitudinal study that involved a retrospective analysis of data in 957 patients in Verona with chronic plaque psoriasis, who were evaluated every 3-4 months at an outpatient dermatology clinic for a median of 2.7 years.
Over the study period, disease flares, defined as an increase in the Psoriasis Area and Severity Index (PASI) of 5 or more points from the previous visit, occurred in 369 patients (38.6%), consistent with known flare rates in psoriasis. Participants in the study (mean age, 61) had median PASI scores of 12 during visits for psoriatic flares compared with PASI scores of 1 during control (no flare) visits (P < .001).
Evaluations of mean concentrations of several air pollutants within 10 miles of the patients over 4,398 visits showed that concentrations were significantly higher in the 60 days prior to the psoriasis flare, compared with control visits that were not related to flares (P < .05), after adjusting for factors including seasonality (by trimester, to adjust for weather conditions and UV/sunlight exposure) and the type of systemic psoriasis treatments patients were receiving (conventional or biological).
Increases in air pollutant levels prior to flares were observed among the 35.8% of patients who had a flare of at least a 50% increase in the PASI score, as well among the 47.2% of patients who had at least a 100% increase in PASI, compared with control visits not involving flares. In addition, mean and area-under-the-curve concentrations of air pollutants were higher in the 60 days before the visits among those with PASI 5 or greater, compared with those with PASI scores below 5, the authors add.
Dr. Bellinato noted that the associations were not limited to any particular subgroup. “The associations with air pollution and flares were observed in the entire population,” he said in an interview.
Vehicle, industry emissions
The pollutants that were measured were those mainly associated with fossil fuel combustion from vehicle and industry emissions, including carbon monoxide, nitrogen dioxide, other nitrogen oxides, benzene, coarse particulate matter (2.5-10.0 μm in diameter) and fine particulate matter (less than 2.5 μm in diameter).
They note that the risk of having a PASI score of 5 or greater was elevated even at thresholds of exposure that are largely considered safe. “Indeed, the risk for having a PASI score of 5 or greater was 40% to 50% higher at exposures as low as 20 μg/m3” of coarse particulate matter and 15 μg/m3 of fine particulate matter in the 60-day period prior to the visits, they write.
The authors referred to evidence linking air pollution with a worsening of a variety of inflammatory cutaneous diseases, including atopic dermatitis and acne, as well as photoaging. Psoriasis flares are known to be triggered by a variety of environmental factors, including infections or certain drugs; however, evidence of a role of air pollution has been lacking. Potential mechanisms linking the exposures to flares include the possibility that exhaust particles can activate skin resident T-cells, “resulting in abnormal production of proinflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukins (ILs), including IL-1α, IL-1β, IL-6, and IL-8.8,” the authors write.
Their results, though inferring a causal relationship, fall short of showing a clear dose–response relationship between higher pollutant levels and an increased risk of psoriasis flares, possibly the result of a smaller sample size of subjects exposed to higher levels of pollution, they add.
Limitations of the study included the definition of flare, which used a clinical score that could be affected by other measurements, they point out, while strengths of the study included the large cohort of patients followed for over 7 years and the availability of daily measurements of air pollutants.
While the study suggests that environmental air pollutant fluctuations may affect psoriasis course,” the authors concluded, “further study is needed to examine whether these findings generalize to other populations and to better understand the mechanisms by which air pollution may affect psoriasis disease activity.”
Dr. Bellinato and four coauthors had no disclosures; the remaining authors had disclosures that included receiving personal fees from pharmaceutical companies that were outside of the submitted work.
A version of this article first appeared on Medscape.com.
Exposure to air pollution – even short term – may play a role in triggering psoriasis flares, according to new research from Italy, which found a significant association between exposure to higher levels of air pollution prior to patients presenting for psoriasis flares at medical visits, compared with visits unrelated to flares.
“We found that higher concentration of different air pollutants was associated with psoriasis flares in patients living in an industrialized city of the Po Valley” in Verona, Italy, report the authors of the study, published in JAMA Dermatology.
The findings underscore the need for clinicians to “consider environmental/external triggers in patients with chronic inflammatory diseases experiencing flares,” first author Francesco Bellinato, MD, of the Section of Dermatology and Venereology, University of Verona, Italy, told this news organization.
He and his coauthors conducted a case-crossover and cross-sectional longitudinal study that involved a retrospective analysis of data in 957 patients in Verona with chronic plaque psoriasis, who were evaluated every 3-4 months at an outpatient dermatology clinic for a median of 2.7 years.
Over the study period, disease flares, defined as an increase in the Psoriasis Area and Severity Index (PASI) of 5 or more points from the previous visit, occurred in 369 patients (38.6%), consistent with known flare rates in psoriasis. Participants in the study (mean age, 61) had median PASI scores of 12 during visits for psoriatic flares compared with PASI scores of 1 during control (no flare) visits (P < .001).
Evaluations of mean concentrations of several air pollutants within 10 miles of the patients over 4,398 visits showed that concentrations were significantly higher in the 60 days prior to the psoriasis flare, compared with control visits that were not related to flares (P < .05), after adjusting for factors including seasonality (by trimester, to adjust for weather conditions and UV/sunlight exposure) and the type of systemic psoriasis treatments patients were receiving (conventional or biological).
Increases in air pollutant levels prior to flares were observed among the 35.8% of patients who had a flare of at least a 50% increase in the PASI score, as well among the 47.2% of patients who had at least a 100% increase in PASI, compared with control visits not involving flares. In addition, mean and area-under-the-curve concentrations of air pollutants were higher in the 60 days before the visits among those with PASI 5 or greater, compared with those with PASI scores below 5, the authors add.
Dr. Bellinato noted that the associations were not limited to any particular subgroup. “The associations with air pollution and flares were observed in the entire population,” he said in an interview.
Vehicle, industry emissions
The pollutants that were measured were those mainly associated with fossil fuel combustion from vehicle and industry emissions, including carbon monoxide, nitrogen dioxide, other nitrogen oxides, benzene, coarse particulate matter (2.5-10.0 μm in diameter) and fine particulate matter (less than 2.5 μm in diameter).
They note that the risk of having a PASI score of 5 or greater was elevated even at thresholds of exposure that are largely considered safe. “Indeed, the risk for having a PASI score of 5 or greater was 40% to 50% higher at exposures as low as 20 μg/m3” of coarse particulate matter and 15 μg/m3 of fine particulate matter in the 60-day period prior to the visits, they write.
The authors referred to evidence linking air pollution with a worsening of a variety of inflammatory cutaneous diseases, including atopic dermatitis and acne, as well as photoaging. Psoriasis flares are known to be triggered by a variety of environmental factors, including infections or certain drugs; however, evidence of a role of air pollution has been lacking. Potential mechanisms linking the exposures to flares include the possibility that exhaust particles can activate skin resident T-cells, “resulting in abnormal production of proinflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukins (ILs), including IL-1α, IL-1β, IL-6, and IL-8.8,” the authors write.
Their results, though inferring a causal relationship, fall short of showing a clear dose–response relationship between higher pollutant levels and an increased risk of psoriasis flares, possibly the result of a smaller sample size of subjects exposed to higher levels of pollution, they add.
Limitations of the study included the definition of flare, which used a clinical score that could be affected by other measurements, they point out, while strengths of the study included the large cohort of patients followed for over 7 years and the availability of daily measurements of air pollutants.
While the study suggests that environmental air pollutant fluctuations may affect psoriasis course,” the authors concluded, “further study is needed to examine whether these findings generalize to other populations and to better understand the mechanisms by which air pollution may affect psoriasis disease activity.”
Dr. Bellinato and four coauthors had no disclosures; the remaining authors had disclosures that included receiving personal fees from pharmaceutical companies that were outside of the submitted work.
A version of this article first appeared on Medscape.com.
FROM JAMA DERMATOLOGY
DMTs tied to lower MS relapse during reproductive therapy
WEST PALM BEACH, FLA. – , new research suggests. In a cohort study of women undergoing ART, those who did not receive DMTs had a significantly higher relapse risk than their peers who were treated with the drugs.
In addition, the likelihood of achieving pregnancy through ART while having MS appeared favorable, researchers noted.
“In this modern case series and the largest cohort to date, we identified a lower risk of relapses after ART than previously reported,” Edith L. Graham, MD, of the department of neurology, Northwestern University, Chicago, and colleagues wrote. “Importantly, continuing DMT during ART may reduce risk of relapse during this period of marked hormonal fluctuations and stressors,” they added.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Study details
Previous research shows a wide range of relapse risk in patients with MS undergoing ART.
To investigate the potential role of DMTs in mitigating relapse risk, the researchers evaluated data on 37 women with either relapsing-remitting MS (n = 31) or clinically isolated syndrome (CIS; n = 6) who underwent ART. The women all had low disability, with a median Expanded Disability Status Scale (EDSS) score of 1.0. All participants had undergone one to five cycles of reproductive therapy between 2010 and 2021.
Most (78%) were receiving ART because of infertility or a need for preimplantation genetic testing, whereas 22% were undergoing the treatment for the preservation of fertility. Average age of the participants was 35 years and average disease duration was 7.4 years.
Among 19 of the 37 patients who were taking DMTs prior to ART, 10 remained on the medication throughout ovarian hyperstimulation.
In those who received DMTs in the 12 months prior to ART, treatment included glatiramer acetate (n = 9), interferons (n = 3), and dimethyl fumarate (n = 1). Three participants received B-cell–depleting agents.
In addition, three women received medication in response to a rebound after discontinuation. Of these, two received fingolimod and one natalizumab.
Five patients (13.5%) experienced MS relapses in the 12 months following ART therapy. Among those experiencing relapse, none were treated with DMTs during the preceding 12 months.
Of the relapses, three occurred within 3 months of the ART treatment, one within 6 months, and one within 12 months.
High rate of successful pregnancy
Overall, 24 of 29 women (83%) underwent in vitro fertilization (IVF) with embryo transfer as part of ART achieved pregnancy. The remaining five patients were undergoing egg cryopreservation.
Although 14 of the 24 who achieved pregnancy were on DMTs and 2 of 5 who did not achieve pregnancy were on the therapies, Dr. Graham noted, “these numbers seem too small to draw conclusions.”
In particular, patients may benefit from treatment with rituximab or ocrelizumab 3-6 months prior to ART, “which gives better protection during ART cycle with low risk of fetal exposure,” she said.
“Treatment does not need to be discontinued if undergoing embryo banking only,” Dr. Graham added. “The risk to the fetus occurs only after embryo transfer.”
Although there is a lack of research examining whether MS relapse lowers the chance of pregnancy, Dr. Graham noted, “in theory, relapsing MS may compromise ART success because [patients] may have a narrower window to undergo ART treatments if they are trying to mitigate DMT exposure to the fetus.”
However, the study’s results generally suggest favorable outcomes with ART among women with MS, she added. “We found that overall ART is actually very successful among people with MS. I was actually very surprised by this high rate of successful pregnancy,” Dr. Graham said.
She noted that as women with MS increasingly undergo IVF as well as egg cryopreservation, research on these issues is gaining importance for clinicians. “This is going to be something that MS specialists need to know more about, particularly the safety of ART in their patients,” said Dr. Graham.
“What’s important is there are no [formal] recommendations along these lines, so this represents an opportunity to get the word out to clinicians that you want to make sure patients with MS are protected throughout the ART cycle and that you’re not discontinuing their DMT too early,” she added.
Protective against relapse?
Commenting on the study, Jiwon Oh, MD, PhD, medical director of the Barlo Multiple Sclerosis Program at St. Michael’s Hospital, University of Toronto, noted that, while there are many guidelines/recommendations regarding use of older DMTs peripregnancy, data on many newer therapies is more limited.
“Often, when people do not have definitive evidence, they tend to take a conservative approach, which is why there is likely reluctance to keep patients on DMTs during ART as well as in early pregnancy,” said Dr. Oh, who was not involved in the research.
Importantly, there is also no definitive evidence of a relationship between MS relapses and ART success or pregnancy outcomes, she noted. However, “from a common-sense perspective, most clinicians worry that extreme stress or disability may negatively affect both ART and pregnancy outcomes,” she added.
Dr. Oh agreed that ocrelizumab is an appropriate choice in terms of preventing relapse during ART. “Ocrevus is one of our highest-efficacy DMTs and is only dosed every 6 months. So this allows for ART cycles and conception without worrying about fetal drug exposure and the drug affecting ART cycles,” she said.
She noted the study’s findings “are in keeping with some prior studies, but not others, demonstrating there may be a higher risk of relapse with ART” in patients who are not taking a DMT.
“However, in my mind the most important conclusion from this study is that being on a DMT seems to be protective of relapse risk, which is an important point that will be useful to provide patients with clinical guidance,” Dr. Oh said.
Dr. Graham reported having received consulting fees from Genentech. Dr. Oh reported having received consulting or speaking fees from Alexion, Biogen Idec, BMS, EMD Serono, Genzyme, Novartis, and Roche.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research suggests. In a cohort study of women undergoing ART, those who did not receive DMTs had a significantly higher relapse risk than their peers who were treated with the drugs.
In addition, the likelihood of achieving pregnancy through ART while having MS appeared favorable, researchers noted.
“In this modern case series and the largest cohort to date, we identified a lower risk of relapses after ART than previously reported,” Edith L. Graham, MD, of the department of neurology, Northwestern University, Chicago, and colleagues wrote. “Importantly, continuing DMT during ART may reduce risk of relapse during this period of marked hormonal fluctuations and stressors,” they added.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Study details
Previous research shows a wide range of relapse risk in patients with MS undergoing ART.
To investigate the potential role of DMTs in mitigating relapse risk, the researchers evaluated data on 37 women with either relapsing-remitting MS (n = 31) or clinically isolated syndrome (CIS; n = 6) who underwent ART. The women all had low disability, with a median Expanded Disability Status Scale (EDSS) score of 1.0. All participants had undergone one to five cycles of reproductive therapy between 2010 and 2021.
Most (78%) were receiving ART because of infertility or a need for preimplantation genetic testing, whereas 22% were undergoing the treatment for the preservation of fertility. Average age of the participants was 35 years and average disease duration was 7.4 years.
Among 19 of the 37 patients who were taking DMTs prior to ART, 10 remained on the medication throughout ovarian hyperstimulation.
In those who received DMTs in the 12 months prior to ART, treatment included glatiramer acetate (n = 9), interferons (n = 3), and dimethyl fumarate (n = 1). Three participants received B-cell–depleting agents.
In addition, three women received medication in response to a rebound after discontinuation. Of these, two received fingolimod and one natalizumab.
Five patients (13.5%) experienced MS relapses in the 12 months following ART therapy. Among those experiencing relapse, none were treated with DMTs during the preceding 12 months.
Of the relapses, three occurred within 3 months of the ART treatment, one within 6 months, and one within 12 months.
High rate of successful pregnancy
Overall, 24 of 29 women (83%) underwent in vitro fertilization (IVF) with embryo transfer as part of ART achieved pregnancy. The remaining five patients were undergoing egg cryopreservation.
Although 14 of the 24 who achieved pregnancy were on DMTs and 2 of 5 who did not achieve pregnancy were on the therapies, Dr. Graham noted, “these numbers seem too small to draw conclusions.”
In particular, patients may benefit from treatment with rituximab or ocrelizumab 3-6 months prior to ART, “which gives better protection during ART cycle with low risk of fetal exposure,” she said.
“Treatment does not need to be discontinued if undergoing embryo banking only,” Dr. Graham added. “The risk to the fetus occurs only after embryo transfer.”
Although there is a lack of research examining whether MS relapse lowers the chance of pregnancy, Dr. Graham noted, “in theory, relapsing MS may compromise ART success because [patients] may have a narrower window to undergo ART treatments if they are trying to mitigate DMT exposure to the fetus.”
However, the study’s results generally suggest favorable outcomes with ART among women with MS, she added. “We found that overall ART is actually very successful among people with MS. I was actually very surprised by this high rate of successful pregnancy,” Dr. Graham said.
She noted that as women with MS increasingly undergo IVF as well as egg cryopreservation, research on these issues is gaining importance for clinicians. “This is going to be something that MS specialists need to know more about, particularly the safety of ART in their patients,” said Dr. Graham.
“What’s important is there are no [formal] recommendations along these lines, so this represents an opportunity to get the word out to clinicians that you want to make sure patients with MS are protected throughout the ART cycle and that you’re not discontinuing their DMT too early,” she added.
Protective against relapse?
Commenting on the study, Jiwon Oh, MD, PhD, medical director of the Barlo Multiple Sclerosis Program at St. Michael’s Hospital, University of Toronto, noted that, while there are many guidelines/recommendations regarding use of older DMTs peripregnancy, data on many newer therapies is more limited.
“Often, when people do not have definitive evidence, they tend to take a conservative approach, which is why there is likely reluctance to keep patients on DMTs during ART as well as in early pregnancy,” said Dr. Oh, who was not involved in the research.
Importantly, there is also no definitive evidence of a relationship between MS relapses and ART success or pregnancy outcomes, she noted. However, “from a common-sense perspective, most clinicians worry that extreme stress or disability may negatively affect both ART and pregnancy outcomes,” she added.
Dr. Oh agreed that ocrelizumab is an appropriate choice in terms of preventing relapse during ART. “Ocrevus is one of our highest-efficacy DMTs and is only dosed every 6 months. So this allows for ART cycles and conception without worrying about fetal drug exposure and the drug affecting ART cycles,” she said.
She noted the study’s findings “are in keeping with some prior studies, but not others, demonstrating there may be a higher risk of relapse with ART” in patients who are not taking a DMT.
“However, in my mind the most important conclusion from this study is that being on a DMT seems to be protective of relapse risk, which is an important point that will be useful to provide patients with clinical guidance,” Dr. Oh said.
Dr. Graham reported having received consulting fees from Genentech. Dr. Oh reported having received consulting or speaking fees from Alexion, Biogen Idec, BMS, EMD Serono, Genzyme, Novartis, and Roche.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research suggests. In a cohort study of women undergoing ART, those who did not receive DMTs had a significantly higher relapse risk than their peers who were treated with the drugs.
In addition, the likelihood of achieving pregnancy through ART while having MS appeared favorable, researchers noted.
“In this modern case series and the largest cohort to date, we identified a lower risk of relapses after ART than previously reported,” Edith L. Graham, MD, of the department of neurology, Northwestern University, Chicago, and colleagues wrote. “Importantly, continuing DMT during ART may reduce risk of relapse during this period of marked hormonal fluctuations and stressors,” they added.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Study details
Previous research shows a wide range of relapse risk in patients with MS undergoing ART.
To investigate the potential role of DMTs in mitigating relapse risk, the researchers evaluated data on 37 women with either relapsing-remitting MS (n = 31) or clinically isolated syndrome (CIS; n = 6) who underwent ART. The women all had low disability, with a median Expanded Disability Status Scale (EDSS) score of 1.0. All participants had undergone one to five cycles of reproductive therapy between 2010 and 2021.
Most (78%) were receiving ART because of infertility or a need for preimplantation genetic testing, whereas 22% were undergoing the treatment for the preservation of fertility. Average age of the participants was 35 years and average disease duration was 7.4 years.
Among 19 of the 37 patients who were taking DMTs prior to ART, 10 remained on the medication throughout ovarian hyperstimulation.
In those who received DMTs in the 12 months prior to ART, treatment included glatiramer acetate (n = 9), interferons (n = 3), and dimethyl fumarate (n = 1). Three participants received B-cell–depleting agents.
In addition, three women received medication in response to a rebound after discontinuation. Of these, two received fingolimod and one natalizumab.
Five patients (13.5%) experienced MS relapses in the 12 months following ART therapy. Among those experiencing relapse, none were treated with DMTs during the preceding 12 months.
Of the relapses, three occurred within 3 months of the ART treatment, one within 6 months, and one within 12 months.
High rate of successful pregnancy
Overall, 24 of 29 women (83%) underwent in vitro fertilization (IVF) with embryo transfer as part of ART achieved pregnancy. The remaining five patients were undergoing egg cryopreservation.
Although 14 of the 24 who achieved pregnancy were on DMTs and 2 of 5 who did not achieve pregnancy were on the therapies, Dr. Graham noted, “these numbers seem too small to draw conclusions.”
In particular, patients may benefit from treatment with rituximab or ocrelizumab 3-6 months prior to ART, “which gives better protection during ART cycle with low risk of fetal exposure,” she said.
“Treatment does not need to be discontinued if undergoing embryo banking only,” Dr. Graham added. “The risk to the fetus occurs only after embryo transfer.”
Although there is a lack of research examining whether MS relapse lowers the chance of pregnancy, Dr. Graham noted, “in theory, relapsing MS may compromise ART success because [patients] may have a narrower window to undergo ART treatments if they are trying to mitigate DMT exposure to the fetus.”
However, the study’s results generally suggest favorable outcomes with ART among women with MS, she added. “We found that overall ART is actually very successful among people with MS. I was actually very surprised by this high rate of successful pregnancy,” Dr. Graham said.
She noted that as women with MS increasingly undergo IVF as well as egg cryopreservation, research on these issues is gaining importance for clinicians. “This is going to be something that MS specialists need to know more about, particularly the safety of ART in their patients,” said Dr. Graham.
“What’s important is there are no [formal] recommendations along these lines, so this represents an opportunity to get the word out to clinicians that you want to make sure patients with MS are protected throughout the ART cycle and that you’re not discontinuing their DMT too early,” she added.
Protective against relapse?
Commenting on the study, Jiwon Oh, MD, PhD, medical director of the Barlo Multiple Sclerosis Program at St. Michael’s Hospital, University of Toronto, noted that, while there are many guidelines/recommendations regarding use of older DMTs peripregnancy, data on many newer therapies is more limited.
“Often, when people do not have definitive evidence, they tend to take a conservative approach, which is why there is likely reluctance to keep patients on DMTs during ART as well as in early pregnancy,” said Dr. Oh, who was not involved in the research.
Importantly, there is also no definitive evidence of a relationship between MS relapses and ART success or pregnancy outcomes, she noted. However, “from a common-sense perspective, most clinicians worry that extreme stress or disability may negatively affect both ART and pregnancy outcomes,” she added.
Dr. Oh agreed that ocrelizumab is an appropriate choice in terms of preventing relapse during ART. “Ocrevus is one of our highest-efficacy DMTs and is only dosed every 6 months. So this allows for ART cycles and conception without worrying about fetal drug exposure and the drug affecting ART cycles,” she said.
She noted the study’s findings “are in keeping with some prior studies, but not others, demonstrating there may be a higher risk of relapse with ART” in patients who are not taking a DMT.
“However, in my mind the most important conclusion from this study is that being on a DMT seems to be protective of relapse risk, which is an important point that will be useful to provide patients with clinical guidance,” Dr. Oh said.
Dr. Graham reported having received consulting fees from Genentech. Dr. Oh reported having received consulting or speaking fees from Alexion, Biogen Idec, BMS, EMD Serono, Genzyme, Novartis, and Roche.
A version of this article first appeared on Medscape.com.
REPORTING FROM ACTRIMS FORUM 2022
Radioactive iodine shows no benefit in low-risk thyroid cancer
, suggesting these patients can be spared the previously common treatment.
The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.
The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.
While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”
However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.
Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.
The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
ESTIMABL2 trial
The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.
Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).
Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.
Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.
After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.
Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).
Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.
There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.
Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.
The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted.
“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.
“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
Patients spared costs, work losses
Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.
For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.
“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.
A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.
“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.
Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
Some continue radioiodine use, but lobectomies add to decline
Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.
“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”
In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.
“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.
The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, suggesting these patients can be spared the previously common treatment.
The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.
The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.
While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”
However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.
Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.
The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
ESTIMABL2 trial
The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.
Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).
Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.
Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.
After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.
Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).
Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.
There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.
Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.
The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted.
“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.
“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
Patients spared costs, work losses
Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.
For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.
“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.
A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.
“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.
Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
Some continue radioiodine use, but lobectomies add to decline
Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.
“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”
In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.
“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.
The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, suggesting these patients can be spared the previously common treatment.
The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.
The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.
While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”
However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.
Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.
The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
ESTIMABL2 trial
The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.
Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).
Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.
Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.
After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.
Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).
Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.
There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.
Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.
The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted.
“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.
“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
Patients spared costs, work losses
Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.
For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.
“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.
A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.
“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.
Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
Some continue radioiodine use, but lobectomies add to decline
Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.
“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”
In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.
“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.
The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Gut microbiome species predict type 2 diabetes
according to results from a 15-year follow-up study of more than 5,000 people in Finland.
“We are not aware of previous long-term prospective studies of the associations between type 2 diabetes and the gut microbiome similar to the current study,” stated the authors of the study, published online Jan. 31, 2022, in Diabetes Care.
Though requiring further validation, the results “build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome,” the authors wrote.
The findings are from a prospective study of data on fecal samples from 5,572 people in Finland in 2002 in the FINRISK 2002 population cohort. In 2017, the samples were sent for sequencing as follow-up.
Of note, the study excluded people with prevalent diabetes at baseline, including those being treated with antidiabetic drugs such as metformin.
Four species, two clusters associated with type 2 diabetes development
Over a median follow-up of 15.8 years, 432 (7.8%) participants went on to have a diagnosis of type 2 diabetes, and the presence of four species and two clusters at baseline were significantly associated with the development of type 2 diabetes.
The four species include Clostridium citroniae (hazard ratio, 1.21; unadjusted P = .02), C. bolteae (HR, 1.20; unadjusted P = .01), Tyzzerella nexilis (HR, 1.17; unadjusted P = .03), and Ruminococcus gnavus (HR, 1.17; P = .04).
And the two positively associated clusters mostly consisted of the same species (both HR, 1.18).
Importantly, the associations were nearly the same among participants in eastern and western Finland, which are known for having unique genetic as well as lifestyle differences that impact morbidity and mortality.
“Three of these taxa could be clustered together by proportional abundance in both geographic areas, and combined abundance of the four taxa was also predictive of incident type 2 diabetes,” the authors wrote.
They noted that the identified species have been previously associated with type 2 diabetes and appear to be linked in some ways to the quality of diet and with other metabolic diseases, such as fatty liver disease.
C. citroniae, for instance, has been associated with trimethylamine N-oxide (TMAO), a compound likely linked to the intake of red meat, and the authors noted that a direct association between red meat intake and type 2 diabetes risk has been known for more than 15 years.
TMAO has also been associated with adipose tissue inflammation and impeded hepatic insulin signaling, which are all involved in increased insulin resistance, high blood glucose levels, and type 2 diabetes, the authors explained.
R. gnavus has been previously associated with obesity in humans and animals. And the bacterial species is also “potentially related to glucose metabolism regulation and linked to increases in inflammatory cytokines, both of which are related to type 2 diabetes pathophysiology,” the authors reported.
Stepping stone toward improved prediction
Coauthor Teemu J. Niiranen, MD, PhD, of the division of medicine, Turku (Finland) University Hospital, noted that, while prior studies have linked type 2 diabetes with distinctive characteristics of gut microbiome composition, most studies have not included prospective data, and long-term studies have been lacking.
Furthermore, many of the studies could have been confounded by the use of antidiabetic drugs that could influence gut microbiome composition, including metformin, which was excluded in the current study.
“We avoid several of the biases related to cross-sectional studies, such as the confounding effects of diabetes medications,” Dr. Niiranen said in an interview.
“We also know the temporal sequence of the exposure and the outcome, and that the changes in the gut microbiome preceded the development of diabetes,” he said. “All in all, a cohort study like this provides a much greater level of evidence than cross-sectional studies.”
Dr. Niiranen noted, however, that “although we demonstrate that certain gut microbiome changes are associated with greater risk of future diabetes, we are still quite far from clinical use.”
In addition to needing to replicate the results in other ethnic groups and locations, “we would need to find optimal clinical cutoffs for clinical decision-making and demonstrate the amount increase in predictive ability, compared with conventional diabetes risk factors,” he said.
The study nevertheless “serves as a stepping stone toward the goal of improved prediction and the development of effective treatments for type 2 diabetes through modification of the gut microbiome,” the authors wrote.
Other research has shed light on gut bacteria that appear to be linked to the prevention rather than the development of diabetes, identifying species that help produce butyrate, a short-chain fatty acid that may in fact provide protection against type 2 diabetes.
And additional research does suggest potential clinical implications. Efforts to improve insulin sensitivity via the gut through fecal microbial transplantation are also making headway, with an oral capsule formulation showing benefit among patients with severe obesity.
The research was funded in part by grants from the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Sigrid Jusélius Foundation, and the Academy of Finland.
A version of this article first appeared on Medscape.com.
according to results from a 15-year follow-up study of more than 5,000 people in Finland.
“We are not aware of previous long-term prospective studies of the associations between type 2 diabetes and the gut microbiome similar to the current study,” stated the authors of the study, published online Jan. 31, 2022, in Diabetes Care.
Though requiring further validation, the results “build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome,” the authors wrote.
The findings are from a prospective study of data on fecal samples from 5,572 people in Finland in 2002 in the FINRISK 2002 population cohort. In 2017, the samples were sent for sequencing as follow-up.
Of note, the study excluded people with prevalent diabetes at baseline, including those being treated with antidiabetic drugs such as metformin.
Four species, two clusters associated with type 2 diabetes development
Over a median follow-up of 15.8 years, 432 (7.8%) participants went on to have a diagnosis of type 2 diabetes, and the presence of four species and two clusters at baseline were significantly associated with the development of type 2 diabetes.
The four species include Clostridium citroniae (hazard ratio, 1.21; unadjusted P = .02), C. bolteae (HR, 1.20; unadjusted P = .01), Tyzzerella nexilis (HR, 1.17; unadjusted P = .03), and Ruminococcus gnavus (HR, 1.17; P = .04).
And the two positively associated clusters mostly consisted of the same species (both HR, 1.18).
Importantly, the associations were nearly the same among participants in eastern and western Finland, which are known for having unique genetic as well as lifestyle differences that impact morbidity and mortality.
“Three of these taxa could be clustered together by proportional abundance in both geographic areas, and combined abundance of the four taxa was also predictive of incident type 2 diabetes,” the authors wrote.
They noted that the identified species have been previously associated with type 2 diabetes and appear to be linked in some ways to the quality of diet and with other metabolic diseases, such as fatty liver disease.
C. citroniae, for instance, has been associated with trimethylamine N-oxide (TMAO), a compound likely linked to the intake of red meat, and the authors noted that a direct association between red meat intake and type 2 diabetes risk has been known for more than 15 years.
TMAO has also been associated with adipose tissue inflammation and impeded hepatic insulin signaling, which are all involved in increased insulin resistance, high blood glucose levels, and type 2 diabetes, the authors explained.
R. gnavus has been previously associated with obesity in humans and animals. And the bacterial species is also “potentially related to glucose metabolism regulation and linked to increases in inflammatory cytokines, both of which are related to type 2 diabetes pathophysiology,” the authors reported.
Stepping stone toward improved prediction
Coauthor Teemu J. Niiranen, MD, PhD, of the division of medicine, Turku (Finland) University Hospital, noted that, while prior studies have linked type 2 diabetes with distinctive characteristics of gut microbiome composition, most studies have not included prospective data, and long-term studies have been lacking.
Furthermore, many of the studies could have been confounded by the use of antidiabetic drugs that could influence gut microbiome composition, including metformin, which was excluded in the current study.
“We avoid several of the biases related to cross-sectional studies, such as the confounding effects of diabetes medications,” Dr. Niiranen said in an interview.
“We also know the temporal sequence of the exposure and the outcome, and that the changes in the gut microbiome preceded the development of diabetes,” he said. “All in all, a cohort study like this provides a much greater level of evidence than cross-sectional studies.”
Dr. Niiranen noted, however, that “although we demonstrate that certain gut microbiome changes are associated with greater risk of future diabetes, we are still quite far from clinical use.”
In addition to needing to replicate the results in other ethnic groups and locations, “we would need to find optimal clinical cutoffs for clinical decision-making and demonstrate the amount increase in predictive ability, compared with conventional diabetes risk factors,” he said.
The study nevertheless “serves as a stepping stone toward the goal of improved prediction and the development of effective treatments for type 2 diabetes through modification of the gut microbiome,” the authors wrote.
Other research has shed light on gut bacteria that appear to be linked to the prevention rather than the development of diabetes, identifying species that help produce butyrate, a short-chain fatty acid that may in fact provide protection against type 2 diabetes.
And additional research does suggest potential clinical implications. Efforts to improve insulin sensitivity via the gut through fecal microbial transplantation are also making headway, with an oral capsule formulation showing benefit among patients with severe obesity.
The research was funded in part by grants from the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Sigrid Jusélius Foundation, and the Academy of Finland.
A version of this article first appeared on Medscape.com.
according to results from a 15-year follow-up study of more than 5,000 people in Finland.
“We are not aware of previous long-term prospective studies of the associations between type 2 diabetes and the gut microbiome similar to the current study,” stated the authors of the study, published online Jan. 31, 2022, in Diabetes Care.
Though requiring further validation, the results “build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome,” the authors wrote.
The findings are from a prospective study of data on fecal samples from 5,572 people in Finland in 2002 in the FINRISK 2002 population cohort. In 2017, the samples were sent for sequencing as follow-up.
Of note, the study excluded people with prevalent diabetes at baseline, including those being treated with antidiabetic drugs such as metformin.
Four species, two clusters associated with type 2 diabetes development
Over a median follow-up of 15.8 years, 432 (7.8%) participants went on to have a diagnosis of type 2 diabetes, and the presence of four species and two clusters at baseline were significantly associated with the development of type 2 diabetes.
The four species include Clostridium citroniae (hazard ratio, 1.21; unadjusted P = .02), C. bolteae (HR, 1.20; unadjusted P = .01), Tyzzerella nexilis (HR, 1.17; unadjusted P = .03), and Ruminococcus gnavus (HR, 1.17; P = .04).
And the two positively associated clusters mostly consisted of the same species (both HR, 1.18).
Importantly, the associations were nearly the same among participants in eastern and western Finland, which are known for having unique genetic as well as lifestyle differences that impact morbidity and mortality.
“Three of these taxa could be clustered together by proportional abundance in both geographic areas, and combined abundance of the four taxa was also predictive of incident type 2 diabetes,” the authors wrote.
They noted that the identified species have been previously associated with type 2 diabetes and appear to be linked in some ways to the quality of diet and with other metabolic diseases, such as fatty liver disease.
C. citroniae, for instance, has been associated with trimethylamine N-oxide (TMAO), a compound likely linked to the intake of red meat, and the authors noted that a direct association between red meat intake and type 2 diabetes risk has been known for more than 15 years.
TMAO has also been associated with adipose tissue inflammation and impeded hepatic insulin signaling, which are all involved in increased insulin resistance, high blood glucose levels, and type 2 diabetes, the authors explained.
R. gnavus has been previously associated with obesity in humans and animals. And the bacterial species is also “potentially related to glucose metabolism regulation and linked to increases in inflammatory cytokines, both of which are related to type 2 diabetes pathophysiology,” the authors reported.
Stepping stone toward improved prediction
Coauthor Teemu J. Niiranen, MD, PhD, of the division of medicine, Turku (Finland) University Hospital, noted that, while prior studies have linked type 2 diabetes with distinctive characteristics of gut microbiome composition, most studies have not included prospective data, and long-term studies have been lacking.
Furthermore, many of the studies could have been confounded by the use of antidiabetic drugs that could influence gut microbiome composition, including metformin, which was excluded in the current study.
“We avoid several of the biases related to cross-sectional studies, such as the confounding effects of diabetes medications,” Dr. Niiranen said in an interview.
“We also know the temporal sequence of the exposure and the outcome, and that the changes in the gut microbiome preceded the development of diabetes,” he said. “All in all, a cohort study like this provides a much greater level of evidence than cross-sectional studies.”
Dr. Niiranen noted, however, that “although we demonstrate that certain gut microbiome changes are associated with greater risk of future diabetes, we are still quite far from clinical use.”
In addition to needing to replicate the results in other ethnic groups and locations, “we would need to find optimal clinical cutoffs for clinical decision-making and demonstrate the amount increase in predictive ability, compared with conventional diabetes risk factors,” he said.
The study nevertheless “serves as a stepping stone toward the goal of improved prediction and the development of effective treatments for type 2 diabetes through modification of the gut microbiome,” the authors wrote.
Other research has shed light on gut bacteria that appear to be linked to the prevention rather than the development of diabetes, identifying species that help produce butyrate, a short-chain fatty acid that may in fact provide protection against type 2 diabetes.
And additional research does suggest potential clinical implications. Efforts to improve insulin sensitivity via the gut through fecal microbial transplantation are also making headway, with an oral capsule formulation showing benefit among patients with severe obesity.
The research was funded in part by grants from the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Sigrid Jusélius Foundation, and the Academy of Finland.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE