A consensus working group from numerous international societies has published new guidelines for standards of practice in the treatment of acute ischemic stroke (AIS). The new guidelines differ somewhat from the Joint Commission guideline, released in 2015, primarily by raising the bar for the number of mechanical thrombectomy (MT) procedures that level 1 and level 2 stroke centers should perform annually in order to maintain a minimum safety threshold.
Ryan McVay/Thinkstock
Previous studies have shown lower mortality in high-volume centers, but setting minimum standards can be a challenge, especially in under-served countries and localities. The authors, led by first author Laurent Pierot, MD, PhD, of University Hospital Reims (France), acknowledge that newly established level 2 centers may struggle to meet the minimum requirement for MT procedures, but that this is acceptable as long as the volume is expected to meet the minimum within 12-24 months.
The guidelines were created by a working group of delegates from 13 international societies, including the American Society of Neuroradiology, European Stroke Organization, World Stroke Organization, and the Society of NeuroInterventional Surgery.
The publication in 2015 of studies showing the efficacy of MT in anterior circulation emergent large-vessel occlusion (ELVO) stroke patients reverberated through the stroke care community, but posed a challenge in delivering this therapy to populations in diverse localities that have no access to level 1 stroke centers.
The guidelines, published online in the Journal of NeuroInterventional Surgery, aim to ensure that facilities can handle not only the MT procedure, but also the medical management before, during, and after the procedure.
According to the new guidelines, level 2 centers should handle cases when a level 1 center cannot be reached within 2 hours. Level 2 centers should care for at least 100 AIS patients per year and should also have a relationship with a level 1 center to maintain staff training, teleconsultations, referrals, and other collaborations.
Previous studies have identified 35 or 36 MT procedures annually as a threshold to be considered “high volume,” a category that led to lower mortality. The new recommendations fall below that threshold because they are intended to apply broadly, to regions that may be under-served. In highly developed countries, stroke centers should follow regional or national guidelines that have higher limits.
Level 2 centers should perform at least 50 intracranial thrombectomy procedures for ELVO, and a total of 120 diagnostic or interventional neuroendovascular procedures per year. Individual interventionists should conduct at least 15 intracranial thrombectomy and 50 interventional neuroendovascular procedures per year.
Other recommendations cover additional details about personnel, as well as community and emergency medical services outreach.
In many ways, the recommendations are in line with the Joint Commission (TJC), according to David Tirschwell, MD, who is the medical director for the UW Medicine* Comprehensive Stroke Center at Harborview Medical Center, Seattle. He was not involved in the development of the new guidelines.
Dr. Tirschwell noted one key difference with respect to the number of MT procedures required to qualify. TJC offered no minimum annual procedures for Comprehensive Stroke Centers (equivalent to level 1), and only 15 for Thrombectomy Capable Stroke Centers (level 2), versus 50 in the new guidelines. The minimum procedure numbers are also higher for individual clinicians.
The guidelines also recommend that level 2 centers have at least three interventionalists on staff available at all times, while TJC does not address this element of staffing.
“The higher minimum number of procedures in the new international recommendations is a substantial difference and would make it harder for many hospitals to qualify, compared to the TJC requirements. As such, a lower number of hospitals may qualify, and such a barrier could prevent access to mechanical thrombectomy for many patients. On the other hand, the higher minimum number may ensure a higher quality of care, which can be seen as a strong positive feature,” Dr. Tirschwell said.
A spokesman for the Joint Commission and the American Heart Association indicated that they will review the new guidelines and consider whether to make changes to their 2015 guidelines.
A consensus working group from numerous international societies has published new guidelines for standards of practice in the treatment of acute ischemic stroke (AIS). The new guidelines differ somewhat from the Joint Commission guideline, released in 2015, primarily by raising the bar for the number of mechanical thrombectomy (MT) procedures that level 1 and level 2 stroke centers should perform annually in order to maintain a minimum safety threshold.
Ryan McVay/Thinkstock
Previous studies have shown lower mortality in high-volume centers, but setting minimum standards can be a challenge, especially in under-served countries and localities. The authors, led by first author Laurent Pierot, MD, PhD, of University Hospital Reims (France), acknowledge that newly established level 2 centers may struggle to meet the minimum requirement for MT procedures, but that this is acceptable as long as the volume is expected to meet the minimum within 12-24 months.
The guidelines were created by a working group of delegates from 13 international societies, including the American Society of Neuroradiology, European Stroke Organization, World Stroke Organization, and the Society of NeuroInterventional Surgery.
The publication in 2015 of studies showing the efficacy of MT in anterior circulation emergent large-vessel occlusion (ELVO) stroke patients reverberated through the stroke care community, but posed a challenge in delivering this therapy to populations in diverse localities that have no access to level 1 stroke centers.
The guidelines, published online in the Journal of NeuroInterventional Surgery, aim to ensure that facilities can handle not only the MT procedure, but also the medical management before, during, and after the procedure.
According to the new guidelines, level 2 centers should handle cases when a level 1 center cannot be reached within 2 hours. Level 2 centers should care for at least 100 AIS patients per year and should also have a relationship with a level 1 center to maintain staff training, teleconsultations, referrals, and other collaborations.
Previous studies have identified 35 or 36 MT procedures annually as a threshold to be considered “high volume,” a category that led to lower mortality. The new recommendations fall below that threshold because they are intended to apply broadly, to regions that may be under-served. In highly developed countries, stroke centers should follow regional or national guidelines that have higher limits.
Level 2 centers should perform at least 50 intracranial thrombectomy procedures for ELVO, and a total of 120 diagnostic or interventional neuroendovascular procedures per year. Individual interventionists should conduct at least 15 intracranial thrombectomy and 50 interventional neuroendovascular procedures per year.
Other recommendations cover additional details about personnel, as well as community and emergency medical services outreach.
In many ways, the recommendations are in line with the Joint Commission (TJC), according to David Tirschwell, MD, who is the medical director for the UW Medicine* Comprehensive Stroke Center at Harborview Medical Center, Seattle. He was not involved in the development of the new guidelines.
Dr. Tirschwell noted one key difference with respect to the number of MT procedures required to qualify. TJC offered no minimum annual procedures for Comprehensive Stroke Centers (equivalent to level 1), and only 15 for Thrombectomy Capable Stroke Centers (level 2), versus 50 in the new guidelines. The minimum procedure numbers are also higher for individual clinicians.
The guidelines also recommend that level 2 centers have at least three interventionalists on staff available at all times, while TJC does not address this element of staffing.
“The higher minimum number of procedures in the new international recommendations is a substantial difference and would make it harder for many hospitals to qualify, compared to the TJC requirements. As such, a lower number of hospitals may qualify, and such a barrier could prevent access to mechanical thrombectomy for many patients. On the other hand, the higher minimum number may ensure a higher quality of care, which can be seen as a strong positive feature,” Dr. Tirschwell said.
A spokesman for the Joint Commission and the American Heart Association indicated that they will review the new guidelines and consider whether to make changes to their 2015 guidelines.
A consensus working group from numerous international societies has published new guidelines for standards of practice in the treatment of acute ischemic stroke (AIS). The new guidelines differ somewhat from the Joint Commission guideline, released in 2015, primarily by raising the bar for the number of mechanical thrombectomy (MT) procedures that level 1 and level 2 stroke centers should perform annually in order to maintain a minimum safety threshold.
Ryan McVay/Thinkstock
Previous studies have shown lower mortality in high-volume centers, but setting minimum standards can be a challenge, especially in under-served countries and localities. The authors, led by first author Laurent Pierot, MD, PhD, of University Hospital Reims (France), acknowledge that newly established level 2 centers may struggle to meet the minimum requirement for MT procedures, but that this is acceptable as long as the volume is expected to meet the minimum within 12-24 months.
The guidelines were created by a working group of delegates from 13 international societies, including the American Society of Neuroradiology, European Stroke Organization, World Stroke Organization, and the Society of NeuroInterventional Surgery.
The publication in 2015 of studies showing the efficacy of MT in anterior circulation emergent large-vessel occlusion (ELVO) stroke patients reverberated through the stroke care community, but posed a challenge in delivering this therapy to populations in diverse localities that have no access to level 1 stroke centers.
The guidelines, published online in the Journal of NeuroInterventional Surgery, aim to ensure that facilities can handle not only the MT procedure, but also the medical management before, during, and after the procedure.
According to the new guidelines, level 2 centers should handle cases when a level 1 center cannot be reached within 2 hours. Level 2 centers should care for at least 100 AIS patients per year and should also have a relationship with a level 1 center to maintain staff training, teleconsultations, referrals, and other collaborations.
Previous studies have identified 35 or 36 MT procedures annually as a threshold to be considered “high volume,” a category that led to lower mortality. The new recommendations fall below that threshold because they are intended to apply broadly, to regions that may be under-served. In highly developed countries, stroke centers should follow regional or national guidelines that have higher limits.
Level 2 centers should perform at least 50 intracranial thrombectomy procedures for ELVO, and a total of 120 diagnostic or interventional neuroendovascular procedures per year. Individual interventionists should conduct at least 15 intracranial thrombectomy and 50 interventional neuroendovascular procedures per year.
Other recommendations cover additional details about personnel, as well as community and emergency medical services outreach.
In many ways, the recommendations are in line with the Joint Commission (TJC), according to David Tirschwell, MD, who is the medical director for the UW Medicine* Comprehensive Stroke Center at Harborview Medical Center, Seattle. He was not involved in the development of the new guidelines.
Dr. Tirschwell noted one key difference with respect to the number of MT procedures required to qualify. TJC offered no minimum annual procedures for Comprehensive Stroke Centers (equivalent to level 1), and only 15 for Thrombectomy Capable Stroke Centers (level 2), versus 50 in the new guidelines. The minimum procedure numbers are also higher for individual clinicians.
The guidelines also recommend that level 2 centers have at least three interventionalists on staff available at all times, while TJC does not address this element of staffing.
“The higher minimum number of procedures in the new international recommendations is a substantial difference and would make it harder for many hospitals to qualify, compared to the TJC requirements. As such, a lower number of hospitals may qualify, and such a barrier could prevent access to mechanical thrombectomy for many patients. On the other hand, the higher minimum number may ensure a higher quality of care, which can be seen as a strong positive feature,” Dr. Tirschwell said.
A spokesman for the Joint Commission and the American Heart Association indicated that they will review the new guidelines and consider whether to make changes to their 2015 guidelines.
Women are at increased risk of developing depression during the perimenopausal transition, which can present with menopausal symptoms and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.
pixelheadphoto/ThinkStock
“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”
The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.
Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.
Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.
Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.
Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.
“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”
Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.
There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.
Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.
The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”
Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.
I think the authors of this paper did a beautiful job summarizing a decade or more of very good observational research and even some randomized, controlled trials on a complex topic. This paper is really important because it takes a large body of evidence on the topic and pulls it together in a coherent way by asking specific questions and then looking to the literature to address those questions. The team of 11 experts in the field – led by Dr. Maki, who is a past president of the North American Menopause Society and began this paper as her presidential project – deserves a lot of credit for doing a beautiful job addressing some important questions with the research that is already available.
Dr. Jan Leslie ShifrenPostpartum depression syndrome has been very well characterized, with clear guidelines for diagnosis and treatment. But researchers have identified the menopausal transition as another window of vulnerability for women, another time of dramatic hormonal fluctuations. People often think of perimenopause as a gradual decline in estrogen levels, but it is a time when there can be very high estrogen levels followed by very low estrogen levels. Because of this unpredictability, it makes sense that this is another time period that needs to be well studied.
There are many clinical implications in these guidelines for any provider who cares for women in their 40s and 50s, whether they are gynecologists, family physicians, internists, psychiatrists, or psychologists. These health care practitioners need to be aware that this is a high-risk period for both depressive symptoms and major depression. The authors reported about one-third of premenopausal women complain of depressive symptoms, and yet, in those women experiencing perimenopause, that percentage is between 45% and 68%. Health care practitioners caring for women in this age group need to be aware of, and looking for, these symptoms so they can identify them, address them, let women know that they’re common at this time, and help them get appropriate treatment.
The authors also looked at the literature on the impact of the menopausal transition on sleep and how that can affect depressive symptoms and major depression; it is important for health care providers to think about sleep disruption in women at this age. The domino hypothesis, the theory that hot flashes can lead to sleep disruption that then leads to depressive symptoms of the menopause transition, was examined in a literature review. The authors found some of the literature shows that these symptoms are separate from hot flashes.
Menopausal transition and the association with symptoms of depression is not only looking at hormonal fluctuations but also recognizing this is a time of extraordinary psychosocial and physical change for women. They may have responsibilities for their partners and children as well as for aging parents. They may have their own health problems and the health problems of their partner to handle. Career changes may be happening at this time. This is a very complex psychosocial time in women’s lives that may be complicated by other health issues occurring at the same time.
Jan Leslie Shifren, MD, is director of the Midlife Women’s Health Center in the department of obstetrics and gynecology at Massachusetts General Hospital, Boston. She also is an Ob.Gyn. News editorial board member. Dr. Shifren reported no relevant conflicts of interest.
I think the authors of this paper did a beautiful job summarizing a decade or more of very good observational research and even some randomized, controlled trials on a complex topic. This paper is really important because it takes a large body of evidence on the topic and pulls it together in a coherent way by asking specific questions and then looking to the literature to address those questions. The team of 11 experts in the field – led by Dr. Maki, who is a past president of the North American Menopause Society and began this paper as her presidential project – deserves a lot of credit for doing a beautiful job addressing some important questions with the research that is already available.
Dr. Jan Leslie ShifrenPostpartum depression syndrome has been very well characterized, with clear guidelines for diagnosis and treatment. But researchers have identified the menopausal transition as another window of vulnerability for women, another time of dramatic hormonal fluctuations. People often think of perimenopause as a gradual decline in estrogen levels, but it is a time when there can be very high estrogen levels followed by very low estrogen levels. Because of this unpredictability, it makes sense that this is another time period that needs to be well studied.
There are many clinical implications in these guidelines for any provider who cares for women in their 40s and 50s, whether they are gynecologists, family physicians, internists, psychiatrists, or psychologists. These health care practitioners need to be aware that this is a high-risk period for both depressive symptoms and major depression. The authors reported about one-third of premenopausal women complain of depressive symptoms, and yet, in those women experiencing perimenopause, that percentage is between 45% and 68%. Health care practitioners caring for women in this age group need to be aware of, and looking for, these symptoms so they can identify them, address them, let women know that they’re common at this time, and help them get appropriate treatment.
The authors also looked at the literature on the impact of the menopausal transition on sleep and how that can affect depressive symptoms and major depression; it is important for health care providers to think about sleep disruption in women at this age. The domino hypothesis, the theory that hot flashes can lead to sleep disruption that then leads to depressive symptoms of the menopause transition, was examined in a literature review. The authors found some of the literature shows that these symptoms are separate from hot flashes.
Menopausal transition and the association with symptoms of depression is not only looking at hormonal fluctuations but also recognizing this is a time of extraordinary psychosocial and physical change for women. They may have responsibilities for their partners and children as well as for aging parents. They may have their own health problems and the health problems of their partner to handle. Career changes may be happening at this time. This is a very complex psychosocial time in women’s lives that may be complicated by other health issues occurring at the same time.
Jan Leslie Shifren, MD, is director of the Midlife Women’s Health Center in the department of obstetrics and gynecology at Massachusetts General Hospital, Boston. She also is an Ob.Gyn. News editorial board member. Dr. Shifren reported no relevant conflicts of interest.
Body
I think the authors of this paper did a beautiful job summarizing a decade or more of very good observational research and even some randomized, controlled trials on a complex topic. This paper is really important because it takes a large body of evidence on the topic and pulls it together in a coherent way by asking specific questions and then looking to the literature to address those questions. The team of 11 experts in the field – led by Dr. Maki, who is a past president of the North American Menopause Society and began this paper as her presidential project – deserves a lot of credit for doing a beautiful job addressing some important questions with the research that is already available.
Dr. Jan Leslie ShifrenPostpartum depression syndrome has been very well characterized, with clear guidelines for diagnosis and treatment. But researchers have identified the menopausal transition as another window of vulnerability for women, another time of dramatic hormonal fluctuations. People often think of perimenopause as a gradual decline in estrogen levels, but it is a time when there can be very high estrogen levels followed by very low estrogen levels. Because of this unpredictability, it makes sense that this is another time period that needs to be well studied.
There are many clinical implications in these guidelines for any provider who cares for women in their 40s and 50s, whether they are gynecologists, family physicians, internists, psychiatrists, or psychologists. These health care practitioners need to be aware that this is a high-risk period for both depressive symptoms and major depression. The authors reported about one-third of premenopausal women complain of depressive symptoms, and yet, in those women experiencing perimenopause, that percentage is between 45% and 68%. Health care practitioners caring for women in this age group need to be aware of, and looking for, these symptoms so they can identify them, address them, let women know that they’re common at this time, and help them get appropriate treatment.
The authors also looked at the literature on the impact of the menopausal transition on sleep and how that can affect depressive symptoms and major depression; it is important for health care providers to think about sleep disruption in women at this age. The domino hypothesis, the theory that hot flashes can lead to sleep disruption that then leads to depressive symptoms of the menopause transition, was examined in a literature review. The authors found some of the literature shows that these symptoms are separate from hot flashes.
Menopausal transition and the association with symptoms of depression is not only looking at hormonal fluctuations but also recognizing this is a time of extraordinary psychosocial and physical change for women. They may have responsibilities for their partners and children as well as for aging parents. They may have their own health problems and the health problems of their partner to handle. Career changes may be happening at this time. This is a very complex psychosocial time in women’s lives that may be complicated by other health issues occurring at the same time.
Jan Leslie Shifren, MD, is director of the Midlife Women’s Health Center in the department of obstetrics and gynecology at Massachusetts General Hospital, Boston. She also is an Ob.Gyn. News editorial board member. Dr. Shifren reported no relevant conflicts of interest.
Title
Recognize symptoms of perimenopausal depression
Recognize symptoms of perimenopausal depression
Women are at increased risk of developing depression during the perimenopausal transition, which can present with menopausal symptoms and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.
pixelheadphoto/ThinkStock
“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”
The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.
Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.
Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.
Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.
Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.
“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”
Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.
There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.
Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.
The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”
Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.
Women are at increased risk of developing depression during the perimenopausal transition, which can present with menopausal symptoms and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.
pixelheadphoto/ThinkStock
“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”
The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.
Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.
Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.
Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.
Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.
“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”
Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.
There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.
Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.
The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”
Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.
Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.
By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).
The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.
For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.
Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.
That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.
However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.
Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.
Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).
Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.
By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.
Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.
Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.
However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.
“Evidence of clinical benefit is lacking” for those interventions, they said.
Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.
By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).
The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.
For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.
Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.
That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.
However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.
Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.
Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).
Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.
By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.
Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.
Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.
However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.
“Evidence of clinical benefit is lacking” for those interventions, they said.
Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.
By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).
The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.
For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.
Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.
That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.
However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.
Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.
Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).
Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.
By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.
Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.
Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.
However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.
“Evidence of clinical benefit is lacking” for those interventions, they said.
Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
Clinicians can safely skip imaging for most children with mild traumatic brain injury (mTBI), and should base management and prognostication on clinical decision-making tools and symptom rating scales, according to new practice guidelines issued by a working group of the Centers for Disease Control and Prevention (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2853.
The guidelines were released simultaneously with a systematic review, conducted by the same authors, of the existing literature regarding pediatric mTBI (JAMA Pediatrics 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2847). As the evaluators sorted through the literature to find high-quality studies for this population, the funnel rapidly narrowed: From an initial pool of over 15,000 studies conducted between 1990 and 2015, findings from just 75 studies were eventually included in the systematic review.
The review’s findings formed the basis for the guidelines and allowed Angela Lumba-Brown, MD, a pediatric emergency medicine physician at Stanford (Calif.) University, and her coauthors to ascribe a level of confidence in the inference from study data for a given recommendation. Recommendations also are categorized by strength and accordingly indicate that clinicians “should” or “may” follow them. Exceptions are carved out for practices, such as the use of hypertonic 3% saline solution for acute headache in the ED, that should not be used outside research settings.
In the end, the guidelines cover 19 main topics, sorted into guidance regarding the diagnosis, prognosis, and management and treatment of mTBI in children.
Diagnosis
The recommendations regarding mTBI diagnosis center around determining which children are at risk for significant intracranial injury (ICI). The guidelines recommend, with moderate confidence, that clinicians usually should not obtain a head CT for children with mTBI. Validated clinical decision rules should be used for risk stratification to determine which children can safely avoid imaging and which children should be considered for head CT, wrote Dr. Lumba-Brown and her coauthors. Magnetic resonance imaging is not recommended for initial evaluation of mTBI, nor should skull radiographs be ordered in the absence of clinical suspicion for skull fracture.
From the systematic review, Dr. Lumba-Brown and her colleagues found that several risk factors taken together may mean that significant ICI is more likely. These include patient age younger than 2 years; any vomiting, loss of consciousness, or amnesia; a severe mechanism of injury, severe or worsening headache, or nonfrontal scalp hematoma; a Glasgow Coma Scale (GCS) score of less than 15; and clinical suspicion for skull fracture. Clinicians should give consideration to the risks of ionizing radiation to the head, and balance this against their assessment of risk for severe – and perhaps actionable – injury.
A validated symptom rating scale, used in an age-appropriate way, should be used as part of the evaluation of children with mTBI. For children aged 6 and older, the Graded Symptom Checklist is an appropriate tool within 2 days after injury, while the Post Concussion Symptom Scale as part of computerized neurocognitive testing can differentiate which high school athletes have mTBI when used within 4 days of injury, according to the guidelines, which also identify other validated symptom rating scales.
The guidelines authors recommend, with high confidence, that serum biomarkers should not be used outside of research settings in the diagnosis of mTBI in children at present.
Prognosis
Families should be counseled that symptoms mostly resolve within 1-3 months for up to 80% of children with mTBI, but families also should know that “each child’s recovery from mTBI is unique and will follow its own trajectory,” wrote Dr. Lumba-Brown and her coauthors, in a moderate-strength recommendation.
Some factors have been associated with slower recovery from mTBI, and either upon evaluation for mTBI or in routine sports examinations, families should be told about this potential if risk factors are present, said the guidelines, although the evidence supporting the associations is of “varying strength,” wrote Dr. Lumba-Brown and her coauthors. Children with previous mTBIs and those with a history of premorbid neurologic and psychiatric problems, learning problems, or family and social stress all may have delayed recovery. For children with ICI, lower cognitive ability also is associated with delayed recovery.
Demographic factors such as lower socioeconomic status and being of Hispanic ethnicity also may increase the risk for delayed mTBI recovery. Older children and adolescents may recover more slowly. Those with more severe initial presentation and more symptoms in the immediate post-mTBI phase also may have a slower recovery course, said Dr. Lumba-Brown and her coauthors.
A validated prediction rule can be used in the ED to gather information about these discrete risk factors to guide family counseling, according to the guidelines, which note that research has found that “an empirically derived set of risk factors predicted the risk of persistent post-concussion symptoms at 28 days” for children seen in the ED with mTBI.
During the recovery phase, a combination of tools should be used to track recovery from mTBI; these can include validated symptom scales, validated cognitive testing, reaction time measures, and, in adolescent athletes, balance testing. Using a combination of tools is a valuable strategy, the researchers wrote. “No single assessment tool is strongly predictive of outcome in children with mTBI,” they noted.
When prognosis is poor, or recovery is not proceeding as expected, clinicians should have a low threshold for initiating other interventions and referrals.
Management and treatment
Although the guideline authors acknowledged significant knowledge gaps in all areas of pediatric mTBI diagnosis and management, evidence is especially scant for best practices for treatment, rest, and return to play and school after a child sustains mTBI, said Dr. Lumba-Brown and her coauthors.
However, families should be given information about warning signs for serious head injury and how to monitor symptoms, as well as information about mTBI and the expected recovery course. Other forward-looking instructions should cover the importance of preventing new head injuries, managing the gradual return to normal cognitive and physical activities, and clear instructions regarding return to school and recreational activities. The guideline authors made a strong recommendation to provide this information, with high confidence in the data.
However, little strong evidence points the way to a clear set of criteria for when children are ready for school, play, and athletic participation. These decisions must be customized to the individual child, and decision making, particularly about return to school and academic activities, should be a collaborative affair, with schools, clinicians, and families all communicating to make sure the pace of return to normal life is keeping pace with the child’s recovery. “Because postconcussive symptoms resolve at different rates in different children after mTBI, individualization of return-to-school programming is necessary,” wrote Dr. Lumba-Brown and her coauthors.
The guideline authors cite evidence that “suggests that early rest (within the first 3 days) may be beneficial but that inactivity beyond this period for most children may worsen their self-reported symptoms.”
Psychosocial support may be beneficial for certain children, wrote the researchers, drawing on evidence showing that such support is beneficial in frank TBI, and is probably beneficial in mTBI.
Active rehabilitation as tolerated is recommended after an initial period of rest, with exertion kept to a level that does not exacerbate symptoms. Children should not participate in contact activities until symptoms are fully resolved.
A posttraumatic headache that is severe or worsens in the ED should prompt consideration of emergent neuroimaging, according to the guidelines. In the postacute phase, however, children can have nonopioid analgesia, although parents should know about such risks as rebound headache. When chronic headache follows a mTBI, the guidelines recommend that clinicians refer patients for a multidisciplinary evaluation that can assess the many factors – including analgesic overuse – that can be contributors.
Drawing on the larger body of adult TBI research, the authors recommend that insufficient or disordered sleep be addressed, because “the maintenance of appropriate sleep and the management of disrupted sleep may be a critical target of treatment for the child with mTBI.”
Children who suffer a mTBI may experience cognitive dysfunction as a direct result of injury to the brain or secondary to the effects of other symptoms such as sleep disruptions, headache pain, fatigue, or low tolerance of frustration. Clinicians may want to perform or refer their patients for a neuropsychological evaluation to determine what is causing the cognitive dysfunction, the authors said.
Dr. Lumba-Brown and her coauthors, who formed the CDC’s Pediatric Mild Traumatic Brain Injury Guideline Workgroup, also recommended that clinicians use the term “mild traumatic brain injury” to describe head injuries that cause confusion or disorientation, without loss of consciousness, or loss of consciousness of up to 30 minutes or less, or posttraumatic amnesia of less than 24 hours duration, and that are associated with a GCS of 13-15 by 30 minutes after injury or at the time of initial medical assessment. This practice, they said, may reduce the risk of misinterpretation by medical professionals and the public that can occur when the terms “mTBI,” “concussion,” and “minor head injury” all may refer to the same injury.
The CDC has developed a suite of materials to assist both health care providers and the public in guideline implementation. The agency also is using its HEADS UP campaign to publicize the guidelines and related materials, and plans ongoing evaluation of the guidelines and implementation materials.
Many study authors, including Dr. Lumba-Brown, had relationships with medical device or pharmaceutical companies. The systematic review and guideline development were funded by the CDC.
A growing realization that mTBI can have persistent and significant deleterious effects has informed medical and public attitudes toward concussion in children, which now results in almost 1 million annual ED visits.
Progress at the laboratory bench has elucidated much of the neurometabolic cascade that occurs with the insult of mTBI, and has allowed researchers to document the path of brain healing after injury. Neuroimaging now can go beyond static images to trace neural networks and detect previously unseen and subtle functional deficits engendered by mTBI.
In particular, 21st century magnetic resonance imaging (MRI) has shown increased sensitivity over CT alone. In the TRACK-TBI study, over one in four patients whose CTs were read as normal had MRI findings consistent with trauma-induced pathology. Both multimodal MRI and serum biomarkers show promise, although more research regarding their utility is needed, particularly in the case of proteomic biomarkers.
Still, high-quality studies of pediatric mTBI are scant, and translation of burgeoning research into clinical practice is severely impeded by the numerous knowledge gaps that exist in the field.
Dr. Lumba-Brown and her colleagues have synthesized research that supports a neurobiopsychosocial model of mTBI in children that comes into play most prominently in the postacute phase, when non–injury-related factors such as demographics, socioeconomic status, and premorbid psychological conditions are strong mediators of the recovery trajectory.
With children as with adults, scant research guides the path forward for treatment and recovery from mTBI. For children, clinicians are still grappling with issues surrounding return to full participation in the academic and recreational activities of the school environment.
Data from two currently active studies should help light the way forward, however. The TRACK-TBI study, funded by the National Institutes of Health, will include almost 200 children among its 2,700 enrollees who have sustained all levels of TBI.
The Concussion Assessment, Research, and Education (CARE) Consortium is funded jointly by the National College Athletic Association and the Department of Defense. Between student athletes and military cadets, over 40,000 individuals are now part of the study.
The two studies’ testing modalities and methodologies align, offering the opportunity for a powerful pooled analysis that includes civilians, athletes, and those in the military.
Until then, these guidelines provide a way forward to an individualized approach to the best care for a child with mTBI.
Michael McCrea, PhD, is professor of neurology and neurosurgery, and director of brain injury research at the Medical College of Wisconsin, Milwaukee. Geoff Manley, MD, PhD, is professor of neurologic surgery at the University of California, San Francisco. Neither author reported conflicts of interest. These remarks were drawn from an editorial accompanying the guidelines and systematic review (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2846).
A growing realization that mTBI can have persistent and significant deleterious effects has informed medical and public attitudes toward concussion in children, which now results in almost 1 million annual ED visits.
Progress at the laboratory bench has elucidated much of the neurometabolic cascade that occurs with the insult of mTBI, and has allowed researchers to document the path of brain healing after injury. Neuroimaging now can go beyond static images to trace neural networks and detect previously unseen and subtle functional deficits engendered by mTBI.
In particular, 21st century magnetic resonance imaging (MRI) has shown increased sensitivity over CT alone. In the TRACK-TBI study, over one in four patients whose CTs were read as normal had MRI findings consistent with trauma-induced pathology. Both multimodal MRI and serum biomarkers show promise, although more research regarding their utility is needed, particularly in the case of proteomic biomarkers.
Still, high-quality studies of pediatric mTBI are scant, and translation of burgeoning research into clinical practice is severely impeded by the numerous knowledge gaps that exist in the field.
Dr. Lumba-Brown and her colleagues have synthesized research that supports a neurobiopsychosocial model of mTBI in children that comes into play most prominently in the postacute phase, when non–injury-related factors such as demographics, socioeconomic status, and premorbid psychological conditions are strong mediators of the recovery trajectory.
With children as with adults, scant research guides the path forward for treatment and recovery from mTBI. For children, clinicians are still grappling with issues surrounding return to full participation in the academic and recreational activities of the school environment.
Data from two currently active studies should help light the way forward, however. The TRACK-TBI study, funded by the National Institutes of Health, will include almost 200 children among its 2,700 enrollees who have sustained all levels of TBI.
The Concussion Assessment, Research, and Education (CARE) Consortium is funded jointly by the National College Athletic Association and the Department of Defense. Between student athletes and military cadets, over 40,000 individuals are now part of the study.
The two studies’ testing modalities and methodologies align, offering the opportunity for a powerful pooled analysis that includes civilians, athletes, and those in the military.
Until then, these guidelines provide a way forward to an individualized approach to the best care for a child with mTBI.
Michael McCrea, PhD, is professor of neurology and neurosurgery, and director of brain injury research at the Medical College of Wisconsin, Milwaukee. Geoff Manley, MD, PhD, is professor of neurologic surgery at the University of California, San Francisco. Neither author reported conflicts of interest. These remarks were drawn from an editorial accompanying the guidelines and systematic review (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2846).
Body
A growing realization that mTBI can have persistent and significant deleterious effects has informed medical and public attitudes toward concussion in children, which now results in almost 1 million annual ED visits.
Progress at the laboratory bench has elucidated much of the neurometabolic cascade that occurs with the insult of mTBI, and has allowed researchers to document the path of brain healing after injury. Neuroimaging now can go beyond static images to trace neural networks and detect previously unseen and subtle functional deficits engendered by mTBI.
In particular, 21st century magnetic resonance imaging (MRI) has shown increased sensitivity over CT alone. In the TRACK-TBI study, over one in four patients whose CTs were read as normal had MRI findings consistent with trauma-induced pathology. Both multimodal MRI and serum biomarkers show promise, although more research regarding their utility is needed, particularly in the case of proteomic biomarkers.
Still, high-quality studies of pediatric mTBI are scant, and translation of burgeoning research into clinical practice is severely impeded by the numerous knowledge gaps that exist in the field.
Dr. Lumba-Brown and her colleagues have synthesized research that supports a neurobiopsychosocial model of mTBI in children that comes into play most prominently in the postacute phase, when non–injury-related factors such as demographics, socioeconomic status, and premorbid psychological conditions are strong mediators of the recovery trajectory.
With children as with adults, scant research guides the path forward for treatment and recovery from mTBI. For children, clinicians are still grappling with issues surrounding return to full participation in the academic and recreational activities of the school environment.
Data from two currently active studies should help light the way forward, however. The TRACK-TBI study, funded by the National Institutes of Health, will include almost 200 children among its 2,700 enrollees who have sustained all levels of TBI.
The Concussion Assessment, Research, and Education (CARE) Consortium is funded jointly by the National College Athletic Association and the Department of Defense. Between student athletes and military cadets, over 40,000 individuals are now part of the study.
The two studies’ testing modalities and methodologies align, offering the opportunity for a powerful pooled analysis that includes civilians, athletes, and those in the military.
Until then, these guidelines provide a way forward to an individualized approach to the best care for a child with mTBI.
Michael McCrea, PhD, is professor of neurology and neurosurgery, and director of brain injury research at the Medical College of Wisconsin, Milwaukee. Geoff Manley, MD, PhD, is professor of neurologic surgery at the University of California, San Francisco. Neither author reported conflicts of interest. These remarks were drawn from an editorial accompanying the guidelines and systematic review (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2846).
Title
Guidelines bring mTBI research to the pediatric bedside
Guidelines bring mTBI research to the pediatric bedside
Clinicians can safely skip imaging for most children with mild traumatic brain injury (mTBI), and should base management and prognostication on clinical decision-making tools and symptom rating scales, according to new practice guidelines issued by a working group of the Centers for Disease Control and Prevention (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2853.
The guidelines were released simultaneously with a systematic review, conducted by the same authors, of the existing literature regarding pediatric mTBI (JAMA Pediatrics 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2847). As the evaluators sorted through the literature to find high-quality studies for this population, the funnel rapidly narrowed: From an initial pool of over 15,000 studies conducted between 1990 and 2015, findings from just 75 studies were eventually included in the systematic review.
The review’s findings formed the basis for the guidelines and allowed Angela Lumba-Brown, MD, a pediatric emergency medicine physician at Stanford (Calif.) University, and her coauthors to ascribe a level of confidence in the inference from study data for a given recommendation. Recommendations also are categorized by strength and accordingly indicate that clinicians “should” or “may” follow them. Exceptions are carved out for practices, such as the use of hypertonic 3% saline solution for acute headache in the ED, that should not be used outside research settings.
In the end, the guidelines cover 19 main topics, sorted into guidance regarding the diagnosis, prognosis, and management and treatment of mTBI in children.
Diagnosis
The recommendations regarding mTBI diagnosis center around determining which children are at risk for significant intracranial injury (ICI). The guidelines recommend, with moderate confidence, that clinicians usually should not obtain a head CT for children with mTBI. Validated clinical decision rules should be used for risk stratification to determine which children can safely avoid imaging and which children should be considered for head CT, wrote Dr. Lumba-Brown and her coauthors. Magnetic resonance imaging is not recommended for initial evaluation of mTBI, nor should skull radiographs be ordered in the absence of clinical suspicion for skull fracture.
From the systematic review, Dr. Lumba-Brown and her colleagues found that several risk factors taken together may mean that significant ICI is more likely. These include patient age younger than 2 years; any vomiting, loss of consciousness, or amnesia; a severe mechanism of injury, severe or worsening headache, or nonfrontal scalp hematoma; a Glasgow Coma Scale (GCS) score of less than 15; and clinical suspicion for skull fracture. Clinicians should give consideration to the risks of ionizing radiation to the head, and balance this against their assessment of risk for severe – and perhaps actionable – injury.
A validated symptom rating scale, used in an age-appropriate way, should be used as part of the evaluation of children with mTBI. For children aged 6 and older, the Graded Symptom Checklist is an appropriate tool within 2 days after injury, while the Post Concussion Symptom Scale as part of computerized neurocognitive testing can differentiate which high school athletes have mTBI when used within 4 days of injury, according to the guidelines, which also identify other validated symptom rating scales.
The guidelines authors recommend, with high confidence, that serum biomarkers should not be used outside of research settings in the diagnosis of mTBI in children at present.
Prognosis
Families should be counseled that symptoms mostly resolve within 1-3 months for up to 80% of children with mTBI, but families also should know that “each child’s recovery from mTBI is unique and will follow its own trajectory,” wrote Dr. Lumba-Brown and her coauthors, in a moderate-strength recommendation.
Some factors have been associated with slower recovery from mTBI, and either upon evaluation for mTBI or in routine sports examinations, families should be told about this potential if risk factors are present, said the guidelines, although the evidence supporting the associations is of “varying strength,” wrote Dr. Lumba-Brown and her coauthors. Children with previous mTBIs and those with a history of premorbid neurologic and psychiatric problems, learning problems, or family and social stress all may have delayed recovery. For children with ICI, lower cognitive ability also is associated with delayed recovery.
Demographic factors such as lower socioeconomic status and being of Hispanic ethnicity also may increase the risk for delayed mTBI recovery. Older children and adolescents may recover more slowly. Those with more severe initial presentation and more symptoms in the immediate post-mTBI phase also may have a slower recovery course, said Dr. Lumba-Brown and her coauthors.
A validated prediction rule can be used in the ED to gather information about these discrete risk factors to guide family counseling, according to the guidelines, which note that research has found that “an empirically derived set of risk factors predicted the risk of persistent post-concussion symptoms at 28 days” for children seen in the ED with mTBI.
During the recovery phase, a combination of tools should be used to track recovery from mTBI; these can include validated symptom scales, validated cognitive testing, reaction time measures, and, in adolescent athletes, balance testing. Using a combination of tools is a valuable strategy, the researchers wrote. “No single assessment tool is strongly predictive of outcome in children with mTBI,” they noted.
When prognosis is poor, or recovery is not proceeding as expected, clinicians should have a low threshold for initiating other interventions and referrals.
Management and treatment
Although the guideline authors acknowledged significant knowledge gaps in all areas of pediatric mTBI diagnosis and management, evidence is especially scant for best practices for treatment, rest, and return to play and school after a child sustains mTBI, said Dr. Lumba-Brown and her coauthors.
However, families should be given information about warning signs for serious head injury and how to monitor symptoms, as well as information about mTBI and the expected recovery course. Other forward-looking instructions should cover the importance of preventing new head injuries, managing the gradual return to normal cognitive and physical activities, and clear instructions regarding return to school and recreational activities. The guideline authors made a strong recommendation to provide this information, with high confidence in the data.
However, little strong evidence points the way to a clear set of criteria for when children are ready for school, play, and athletic participation. These decisions must be customized to the individual child, and decision making, particularly about return to school and academic activities, should be a collaborative affair, with schools, clinicians, and families all communicating to make sure the pace of return to normal life is keeping pace with the child’s recovery. “Because postconcussive symptoms resolve at different rates in different children after mTBI, individualization of return-to-school programming is necessary,” wrote Dr. Lumba-Brown and her coauthors.
The guideline authors cite evidence that “suggests that early rest (within the first 3 days) may be beneficial but that inactivity beyond this period for most children may worsen their self-reported symptoms.”
Psychosocial support may be beneficial for certain children, wrote the researchers, drawing on evidence showing that such support is beneficial in frank TBI, and is probably beneficial in mTBI.
Active rehabilitation as tolerated is recommended after an initial period of rest, with exertion kept to a level that does not exacerbate symptoms. Children should not participate in contact activities until symptoms are fully resolved.
A posttraumatic headache that is severe or worsens in the ED should prompt consideration of emergent neuroimaging, according to the guidelines. In the postacute phase, however, children can have nonopioid analgesia, although parents should know about such risks as rebound headache. When chronic headache follows a mTBI, the guidelines recommend that clinicians refer patients for a multidisciplinary evaluation that can assess the many factors – including analgesic overuse – that can be contributors.
Drawing on the larger body of adult TBI research, the authors recommend that insufficient or disordered sleep be addressed, because “the maintenance of appropriate sleep and the management of disrupted sleep may be a critical target of treatment for the child with mTBI.”
Children who suffer a mTBI may experience cognitive dysfunction as a direct result of injury to the brain or secondary to the effects of other symptoms such as sleep disruptions, headache pain, fatigue, or low tolerance of frustration. Clinicians may want to perform or refer their patients for a neuropsychological evaluation to determine what is causing the cognitive dysfunction, the authors said.
Dr. Lumba-Brown and her coauthors, who formed the CDC’s Pediatric Mild Traumatic Brain Injury Guideline Workgroup, also recommended that clinicians use the term “mild traumatic brain injury” to describe head injuries that cause confusion or disorientation, without loss of consciousness, or loss of consciousness of up to 30 minutes or less, or posttraumatic amnesia of less than 24 hours duration, and that are associated with a GCS of 13-15 by 30 minutes after injury or at the time of initial medical assessment. This practice, they said, may reduce the risk of misinterpretation by medical professionals and the public that can occur when the terms “mTBI,” “concussion,” and “minor head injury” all may refer to the same injury.
The CDC has developed a suite of materials to assist both health care providers and the public in guideline implementation. The agency also is using its HEADS UP campaign to publicize the guidelines and related materials, and plans ongoing evaluation of the guidelines and implementation materials.
Many study authors, including Dr. Lumba-Brown, had relationships with medical device or pharmaceutical companies. The systematic review and guideline development were funded by the CDC.
Clinicians can safely skip imaging for most children with mild traumatic brain injury (mTBI), and should base management and prognostication on clinical decision-making tools and symptom rating scales, according to new practice guidelines issued by a working group of the Centers for Disease Control and Prevention (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2853.
The guidelines were released simultaneously with a systematic review, conducted by the same authors, of the existing literature regarding pediatric mTBI (JAMA Pediatrics 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2847). As the evaluators sorted through the literature to find high-quality studies for this population, the funnel rapidly narrowed: From an initial pool of over 15,000 studies conducted between 1990 and 2015, findings from just 75 studies were eventually included in the systematic review.
The review’s findings formed the basis for the guidelines and allowed Angela Lumba-Brown, MD, a pediatric emergency medicine physician at Stanford (Calif.) University, and her coauthors to ascribe a level of confidence in the inference from study data for a given recommendation. Recommendations also are categorized by strength and accordingly indicate that clinicians “should” or “may” follow them. Exceptions are carved out for practices, such as the use of hypertonic 3% saline solution for acute headache in the ED, that should not be used outside research settings.
In the end, the guidelines cover 19 main topics, sorted into guidance regarding the diagnosis, prognosis, and management and treatment of mTBI in children.
Diagnosis
The recommendations regarding mTBI diagnosis center around determining which children are at risk for significant intracranial injury (ICI). The guidelines recommend, with moderate confidence, that clinicians usually should not obtain a head CT for children with mTBI. Validated clinical decision rules should be used for risk stratification to determine which children can safely avoid imaging and which children should be considered for head CT, wrote Dr. Lumba-Brown and her coauthors. Magnetic resonance imaging is not recommended for initial evaluation of mTBI, nor should skull radiographs be ordered in the absence of clinical suspicion for skull fracture.
From the systematic review, Dr. Lumba-Brown and her colleagues found that several risk factors taken together may mean that significant ICI is more likely. These include patient age younger than 2 years; any vomiting, loss of consciousness, or amnesia; a severe mechanism of injury, severe or worsening headache, or nonfrontal scalp hematoma; a Glasgow Coma Scale (GCS) score of less than 15; and clinical suspicion for skull fracture. Clinicians should give consideration to the risks of ionizing radiation to the head, and balance this against their assessment of risk for severe – and perhaps actionable – injury.
A validated symptom rating scale, used in an age-appropriate way, should be used as part of the evaluation of children with mTBI. For children aged 6 and older, the Graded Symptom Checklist is an appropriate tool within 2 days after injury, while the Post Concussion Symptom Scale as part of computerized neurocognitive testing can differentiate which high school athletes have mTBI when used within 4 days of injury, according to the guidelines, which also identify other validated symptom rating scales.
The guidelines authors recommend, with high confidence, that serum biomarkers should not be used outside of research settings in the diagnosis of mTBI in children at present.
Prognosis
Families should be counseled that symptoms mostly resolve within 1-3 months for up to 80% of children with mTBI, but families also should know that “each child’s recovery from mTBI is unique and will follow its own trajectory,” wrote Dr. Lumba-Brown and her coauthors, in a moderate-strength recommendation.
Some factors have been associated with slower recovery from mTBI, and either upon evaluation for mTBI or in routine sports examinations, families should be told about this potential if risk factors are present, said the guidelines, although the evidence supporting the associations is of “varying strength,” wrote Dr. Lumba-Brown and her coauthors. Children with previous mTBIs and those with a history of premorbid neurologic and psychiatric problems, learning problems, or family and social stress all may have delayed recovery. For children with ICI, lower cognitive ability also is associated with delayed recovery.
Demographic factors such as lower socioeconomic status and being of Hispanic ethnicity also may increase the risk for delayed mTBI recovery. Older children and adolescents may recover more slowly. Those with more severe initial presentation and more symptoms in the immediate post-mTBI phase also may have a slower recovery course, said Dr. Lumba-Brown and her coauthors.
A validated prediction rule can be used in the ED to gather information about these discrete risk factors to guide family counseling, according to the guidelines, which note that research has found that “an empirically derived set of risk factors predicted the risk of persistent post-concussion symptoms at 28 days” for children seen in the ED with mTBI.
During the recovery phase, a combination of tools should be used to track recovery from mTBI; these can include validated symptom scales, validated cognitive testing, reaction time measures, and, in adolescent athletes, balance testing. Using a combination of tools is a valuable strategy, the researchers wrote. “No single assessment tool is strongly predictive of outcome in children with mTBI,” they noted.
When prognosis is poor, or recovery is not proceeding as expected, clinicians should have a low threshold for initiating other interventions and referrals.
Management and treatment
Although the guideline authors acknowledged significant knowledge gaps in all areas of pediatric mTBI diagnosis and management, evidence is especially scant for best practices for treatment, rest, and return to play and school after a child sustains mTBI, said Dr. Lumba-Brown and her coauthors.
However, families should be given information about warning signs for serious head injury and how to monitor symptoms, as well as information about mTBI and the expected recovery course. Other forward-looking instructions should cover the importance of preventing new head injuries, managing the gradual return to normal cognitive and physical activities, and clear instructions regarding return to school and recreational activities. The guideline authors made a strong recommendation to provide this information, with high confidence in the data.
However, little strong evidence points the way to a clear set of criteria for when children are ready for school, play, and athletic participation. These decisions must be customized to the individual child, and decision making, particularly about return to school and academic activities, should be a collaborative affair, with schools, clinicians, and families all communicating to make sure the pace of return to normal life is keeping pace with the child’s recovery. “Because postconcussive symptoms resolve at different rates in different children after mTBI, individualization of return-to-school programming is necessary,” wrote Dr. Lumba-Brown and her coauthors.
The guideline authors cite evidence that “suggests that early rest (within the first 3 days) may be beneficial but that inactivity beyond this period for most children may worsen their self-reported symptoms.”
Psychosocial support may be beneficial for certain children, wrote the researchers, drawing on evidence showing that such support is beneficial in frank TBI, and is probably beneficial in mTBI.
Active rehabilitation as tolerated is recommended after an initial period of rest, with exertion kept to a level that does not exacerbate symptoms. Children should not participate in contact activities until symptoms are fully resolved.
A posttraumatic headache that is severe or worsens in the ED should prompt consideration of emergent neuroimaging, according to the guidelines. In the postacute phase, however, children can have nonopioid analgesia, although parents should know about such risks as rebound headache. When chronic headache follows a mTBI, the guidelines recommend that clinicians refer patients for a multidisciplinary evaluation that can assess the many factors – including analgesic overuse – that can be contributors.
Drawing on the larger body of adult TBI research, the authors recommend that insufficient or disordered sleep be addressed, because “the maintenance of appropriate sleep and the management of disrupted sleep may be a critical target of treatment for the child with mTBI.”
Children who suffer a mTBI may experience cognitive dysfunction as a direct result of injury to the brain or secondary to the effects of other symptoms such as sleep disruptions, headache pain, fatigue, or low tolerance of frustration. Clinicians may want to perform or refer their patients for a neuropsychological evaluation to determine what is causing the cognitive dysfunction, the authors said.
Dr. Lumba-Brown and her coauthors, who formed the CDC’s Pediatric Mild Traumatic Brain Injury Guideline Workgroup, also recommended that clinicians use the term “mild traumatic brain injury” to describe head injuries that cause confusion or disorientation, without loss of consciousness, or loss of consciousness of up to 30 minutes or less, or posttraumatic amnesia of less than 24 hours duration, and that are associated with a GCS of 13-15 by 30 minutes after injury or at the time of initial medical assessment. This practice, they said, may reduce the risk of misinterpretation by medical professionals and the public that can occur when the terms “mTBI,” “concussion,” and “minor head injury” all may refer to the same injury.
The CDC has developed a suite of materials to assist both health care providers and the public in guideline implementation. The agency also is using its HEADS UP campaign to publicize the guidelines and related materials, and plans ongoing evaluation of the guidelines and implementation materials.
Many study authors, including Dr. Lumba-Brown, had relationships with medical device or pharmaceutical companies. The systematic review and guideline development were funded by the CDC.
Updated EULAR recommendations on the management of hand osteoarthritis include five overarching principles as well as two new recommendations that reflect new research in the field.
Astrid860/Getty Images
The task force, led by Margreet Kloppenburg, MD, PhD, of the department of rheumatology at Leiden (the Netherlands) University Medical Center, noted that a decade had passed since the first recommendations were published in 2007.
“It was timely to update the recommendations, as many new studies had emerged during this period. In light of this new evidence, many of the 2007 recommendations were modified and new recommendations were added,” wrote Dr. Kloppenburg and her colleagues. The recommendations were published online in Annals of the Rheumatic Diseases.
They noted that the recommendations were targeted to all health professionals across primary and secondary care but also aimed to inform patients about their disease to “support shared decision making.”
In line with other EULAR sets of management recommendations, the update included five overarching principles that cover treatment goals, information and education for patients, individualization of treatment, shared decision making between clinicians and patients, and the need to take into consideration a multidisciplinary and multimodal (pharmacologic and nonpharmacologic) treatment approach.
The authors noted that for a long time hand OA was a “forgotten disease” and this was reflected by the paucity of clinical trials in the area. As a direct consequence, previous recommendations were based on expert opinion rather than evidence.
However, new data allowed the task force to recommend not to treat patients with hand OA with conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). The recommendation achieved the strongest level of evidence and a high level of agreement from the 19-member expert panel, which included 2 patient research partners. The authors said the recommendation was based on newer studies that demonstrated a lack of efficacy of csDMARDs and bDMARDs.
The authors also advised adapting the long-term follow-up of patients with hand OA to individual needs, although they noted this was based on expert opinion alone and that in the absence of a disease-modifying treatment, the goal of follow-up differs from that of many other rheumatic diseases. Individual needs will dictate the degree of follow-up required, based on the severity of symptoms, presence of erosive disease, reevaluation of the use of pharmacologic therapy, and a patient’s wishes and expectations. They also noted that “for most patients, standard radiographic follow-up is not useful at this moment” and that “follow-up does not necessarily have to be performed by a rheumatologist.
“Follow-up will likely increase adherence to nonpharmacological therapies like exercise or orthoses, and provides an opportunity for reevaluation of treatment,” they wrote.
The recommendations advise offering education and training in ergonomic principles and exercises to patients to improve function and muscle strength, as well as considering the use of orthoses in some patients.
Treatment recommendations suggested preferring topical treatments over systemic treatments and that oral analgesics, particularly NSAIDs, should be considered for a limited duration. The authors advised that chondroitin sulfate may be used in patients for pain relief and improvement in functioning and that intra-articular glucocorticoids should not generally be used but may be considered in patients with painful interphalangeal joints. Surgery should be considered for patients with structural abnormalities when other treatment modalities have not been sufficiently effective in relieving pain.
The recommendations were funded by EULAR. Several of the authors reported receiving consultancy fees and/or honoraria as well as research funding from industry.
EULAR has updated its 2007 guidelines for the management of hand osteoarthritis. I find the recommendations helpful, and I have no disagreements.
The authors performed a systematic literature review that was more complete than the original guidelines. In addition, the methodology in developing the guidelines was updated utilizing the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) system to guide the expert opinion. The manuscript presents recommendations that are carefully supported in the text. To understand guidelines, one really needs to read the text.
Dr. Roy D. AltmanThey have developed a set of overarching principles that precede the recommendations. These principles address the goals of therapy, patient education, comorbidities, decision-making involving the patient, and the common need for the multidisciplinary approach.
The update lists a set of research questions, similar to the 2007 recommendations.
The authors group their therapeutic recommendations according to nonpharmacologic, pharmacologic, and surgical approaches, as well as about the need for follow-up. The three nonpharmacologic recommendations include education and training, exercise and muscle strengthening, and the use of orthoses. The pharmacologic approach includes topical therapy as a first-line, oral NSAIDs and analgesics, chondroitin sulfate, and intra-articular injections. There is a negative recommendation for the use of biologics. The surgical recommendation is directed at the relief of pain. The last recommendation emphasizes the need for follow-up and individual care.
The differences between the recommendations include the removal of acetaminophen as a first-line therapy. Indeed, it seems to be barely recommended at all. In addition, there is an emphasis on topical therapy, particularly NSAIDs. The authors are equivocal on the recommendations for intra-articular therapy. Paraffin and local heat are no longer included. The recommendation against biologic therapy is new. They included agents used for rheumatoid arthritis, such as methotrexate, in this negative recommendation.
These new recommendations are an update of guidelines that are over 10 years old. They are practical and helpful. Unfortunately, more research is needed as the present day therapy is often inadequate.
Roy D. Altman, MD, is professor emeritus of medicine in the division of rheumatology and immunology at the University of California, Los Angeles. He is a consultant to Ferring, Flexion, GlaxoSmithKline, Novartis, Olatec, Pfizer, and Sorrento Therapeutics.
EULAR has updated its 2007 guidelines for the management of hand osteoarthritis. I find the recommendations helpful, and I have no disagreements.
The authors performed a systematic literature review that was more complete than the original guidelines. In addition, the methodology in developing the guidelines was updated utilizing the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) system to guide the expert opinion. The manuscript presents recommendations that are carefully supported in the text. To understand guidelines, one really needs to read the text.
Dr. Roy D. AltmanThey have developed a set of overarching principles that precede the recommendations. These principles address the goals of therapy, patient education, comorbidities, decision-making involving the patient, and the common need for the multidisciplinary approach.
The update lists a set of research questions, similar to the 2007 recommendations.
The authors group their therapeutic recommendations according to nonpharmacologic, pharmacologic, and surgical approaches, as well as about the need for follow-up. The three nonpharmacologic recommendations include education and training, exercise and muscle strengthening, and the use of orthoses. The pharmacologic approach includes topical therapy as a first-line, oral NSAIDs and analgesics, chondroitin sulfate, and intra-articular injections. There is a negative recommendation for the use of biologics. The surgical recommendation is directed at the relief of pain. The last recommendation emphasizes the need for follow-up and individual care.
The differences between the recommendations include the removal of acetaminophen as a first-line therapy. Indeed, it seems to be barely recommended at all. In addition, there is an emphasis on topical therapy, particularly NSAIDs. The authors are equivocal on the recommendations for intra-articular therapy. Paraffin and local heat are no longer included. The recommendation against biologic therapy is new. They included agents used for rheumatoid arthritis, such as methotrexate, in this negative recommendation.
These new recommendations are an update of guidelines that are over 10 years old. They are practical and helpful. Unfortunately, more research is needed as the present day therapy is often inadequate.
Roy D. Altman, MD, is professor emeritus of medicine in the division of rheumatology and immunology at the University of California, Los Angeles. He is a consultant to Ferring, Flexion, GlaxoSmithKline, Novartis, Olatec, Pfizer, and Sorrento Therapeutics.
Body
EULAR has updated its 2007 guidelines for the management of hand osteoarthritis. I find the recommendations helpful, and I have no disagreements.
The authors performed a systematic literature review that was more complete than the original guidelines. In addition, the methodology in developing the guidelines was updated utilizing the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) system to guide the expert opinion. The manuscript presents recommendations that are carefully supported in the text. To understand guidelines, one really needs to read the text.
Dr. Roy D. AltmanThey have developed a set of overarching principles that precede the recommendations. These principles address the goals of therapy, patient education, comorbidities, decision-making involving the patient, and the common need for the multidisciplinary approach.
The update lists a set of research questions, similar to the 2007 recommendations.
The authors group their therapeutic recommendations according to nonpharmacologic, pharmacologic, and surgical approaches, as well as about the need for follow-up. The three nonpharmacologic recommendations include education and training, exercise and muscle strengthening, and the use of orthoses. The pharmacologic approach includes topical therapy as a first-line, oral NSAIDs and analgesics, chondroitin sulfate, and intra-articular injections. There is a negative recommendation for the use of biologics. The surgical recommendation is directed at the relief of pain. The last recommendation emphasizes the need for follow-up and individual care.
The differences between the recommendations include the removal of acetaminophen as a first-line therapy. Indeed, it seems to be barely recommended at all. In addition, there is an emphasis on topical therapy, particularly NSAIDs. The authors are equivocal on the recommendations for intra-articular therapy. Paraffin and local heat are no longer included. The recommendation against biologic therapy is new. They included agents used for rheumatoid arthritis, such as methotrexate, in this negative recommendation.
These new recommendations are an update of guidelines that are over 10 years old. They are practical and helpful. Unfortunately, more research is needed as the present day therapy is often inadequate.
Roy D. Altman, MD, is professor emeritus of medicine in the division of rheumatology and immunology at the University of California, Los Angeles. He is a consultant to Ferring, Flexion, GlaxoSmithKline, Novartis, Olatec, Pfizer, and Sorrento Therapeutics.
Title
Update is timely and practical
Update is timely and practical
Updated EULAR recommendations on the management of hand osteoarthritis include five overarching principles as well as two new recommendations that reflect new research in the field.
Astrid860/Getty Images
The task force, led by Margreet Kloppenburg, MD, PhD, of the department of rheumatology at Leiden (the Netherlands) University Medical Center, noted that a decade had passed since the first recommendations were published in 2007.
“It was timely to update the recommendations, as many new studies had emerged during this period. In light of this new evidence, many of the 2007 recommendations were modified and new recommendations were added,” wrote Dr. Kloppenburg and her colleagues. The recommendations were published online in Annals of the Rheumatic Diseases.
They noted that the recommendations were targeted to all health professionals across primary and secondary care but also aimed to inform patients about their disease to “support shared decision making.”
In line with other EULAR sets of management recommendations, the update included five overarching principles that cover treatment goals, information and education for patients, individualization of treatment, shared decision making between clinicians and patients, and the need to take into consideration a multidisciplinary and multimodal (pharmacologic and nonpharmacologic) treatment approach.
The authors noted that for a long time hand OA was a “forgotten disease” and this was reflected by the paucity of clinical trials in the area. As a direct consequence, previous recommendations were based on expert opinion rather than evidence.
However, new data allowed the task force to recommend not to treat patients with hand OA with conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). The recommendation achieved the strongest level of evidence and a high level of agreement from the 19-member expert panel, which included 2 patient research partners. The authors said the recommendation was based on newer studies that demonstrated a lack of efficacy of csDMARDs and bDMARDs.
The authors also advised adapting the long-term follow-up of patients with hand OA to individual needs, although they noted this was based on expert opinion alone and that in the absence of a disease-modifying treatment, the goal of follow-up differs from that of many other rheumatic diseases. Individual needs will dictate the degree of follow-up required, based on the severity of symptoms, presence of erosive disease, reevaluation of the use of pharmacologic therapy, and a patient’s wishes and expectations. They also noted that “for most patients, standard radiographic follow-up is not useful at this moment” and that “follow-up does not necessarily have to be performed by a rheumatologist.
“Follow-up will likely increase adherence to nonpharmacological therapies like exercise or orthoses, and provides an opportunity for reevaluation of treatment,” they wrote.
The recommendations advise offering education and training in ergonomic principles and exercises to patients to improve function and muscle strength, as well as considering the use of orthoses in some patients.
Treatment recommendations suggested preferring topical treatments over systemic treatments and that oral analgesics, particularly NSAIDs, should be considered for a limited duration. The authors advised that chondroitin sulfate may be used in patients for pain relief and improvement in functioning and that intra-articular glucocorticoids should not generally be used but may be considered in patients with painful interphalangeal joints. Surgery should be considered for patients with structural abnormalities when other treatment modalities have not been sufficiently effective in relieving pain.
The recommendations were funded by EULAR. Several of the authors reported receiving consultancy fees and/or honoraria as well as research funding from industry.
Updated EULAR recommendations on the management of hand osteoarthritis include five overarching principles as well as two new recommendations that reflect new research in the field.
Astrid860/Getty Images
The task force, led by Margreet Kloppenburg, MD, PhD, of the department of rheumatology at Leiden (the Netherlands) University Medical Center, noted that a decade had passed since the first recommendations were published in 2007.
“It was timely to update the recommendations, as many new studies had emerged during this period. In light of this new evidence, many of the 2007 recommendations were modified and new recommendations were added,” wrote Dr. Kloppenburg and her colleagues. The recommendations were published online in Annals of the Rheumatic Diseases.
They noted that the recommendations were targeted to all health professionals across primary and secondary care but also aimed to inform patients about their disease to “support shared decision making.”
In line with other EULAR sets of management recommendations, the update included five overarching principles that cover treatment goals, information and education for patients, individualization of treatment, shared decision making between clinicians and patients, and the need to take into consideration a multidisciplinary and multimodal (pharmacologic and nonpharmacologic) treatment approach.
The authors noted that for a long time hand OA was a “forgotten disease” and this was reflected by the paucity of clinical trials in the area. As a direct consequence, previous recommendations were based on expert opinion rather than evidence.
However, new data allowed the task force to recommend not to treat patients with hand OA with conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). The recommendation achieved the strongest level of evidence and a high level of agreement from the 19-member expert panel, which included 2 patient research partners. The authors said the recommendation was based on newer studies that demonstrated a lack of efficacy of csDMARDs and bDMARDs.
The authors also advised adapting the long-term follow-up of patients with hand OA to individual needs, although they noted this was based on expert opinion alone and that in the absence of a disease-modifying treatment, the goal of follow-up differs from that of many other rheumatic diseases. Individual needs will dictate the degree of follow-up required, based on the severity of symptoms, presence of erosive disease, reevaluation of the use of pharmacologic therapy, and a patient’s wishes and expectations. They also noted that “for most patients, standard radiographic follow-up is not useful at this moment” and that “follow-up does not necessarily have to be performed by a rheumatologist.
“Follow-up will likely increase adherence to nonpharmacological therapies like exercise or orthoses, and provides an opportunity for reevaluation of treatment,” they wrote.
The recommendations advise offering education and training in ergonomic principles and exercises to patients to improve function and muscle strength, as well as considering the use of orthoses in some patients.
Treatment recommendations suggested preferring topical treatments over systemic treatments and that oral analgesics, particularly NSAIDs, should be considered for a limited duration. The authors advised that chondroitin sulfate may be used in patients for pain relief and improvement in functioning and that intra-articular glucocorticoids should not generally be used but may be considered in patients with painful interphalangeal joints. Surgery should be considered for patients with structural abnormalities when other treatment modalities have not been sufficiently effective in relieving pain.
The recommendations were funded by EULAR. Several of the authors reported receiving consultancy fees and/or honoraria as well as research funding from industry.
The European Society for Medical Oncology (ESMO) has published a proposed scale that would rank molecular targets for various cancers by how well they can be treated with new or emerging drugs.
The ESMO Scale of Clinical Actionability for Molecular Targets is designed to “harmonize and standardize the reporting and interpretation of clinically relevant genomics data,” according to Joaquin Mateo, MD, PhD, from the Vall d’Hebron Institute of Oncology in Barcelona, Spain, and his fellow members of the ESMO Translational Research and Precision Medicine Working Group.
“A major challenge for oncologists in the clinic is to distinguish between findings that represent proven clinical value or potential value based on preliminary clinical or preclinical evidence from hypothetical gene-drug matches and findings that are currently irrelevant for clinical practice,” they wrote in Annals of Oncology.
The scale groups targets into one of six tiers based on levels of evidence ranging from the gold standard of prospective, randomized clinical trials to targets for which there are no evidence and only hypothetical actionability. The primary goal is to help oncologists assign priority to potential targets when they review results of gene-sequencing panels for individual patients, according to the developers.
Briefly, the six tiers are:
Tier I includes targets that are agreed to be suitable for routine use and a recommended specific drug when a specific molecular alteration is detected. Examples include trastuzumab for human epidermal growth factor receptor 2 (HER2)–positive breast cancer, and inhibitors of epidermal growth factor receptor (EGFR) in patients with non–small cell lung cancer positive for EGFR mutations.
Tier II includes “investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed.” This tier includes agents that work in the phosphatidylinostiol 3-kinase pathway.
Tier III is similar to Tier II, in that it includes investigational targets that define a patient population with proven benefit from a targeted therapy, but in this case the target is detected in a different tumor type that has not previously been studied. For example, the targeted agent vemurafenib (Zelboraf), which extends survival of patients with metastatic melanomas carrying the BRAF V600E mutation, has only limited activity against BRAF-mutated colorectal cancers.
Tier IV includes targets with preclinical evidence of actionability.
Tier V includes targets with “evidence of relevant antitumor activity, not resulting in clinical meaningful benefit as single treatment but supporting development of cotargeting approaches.” The authors cite the example of PIK3CA inhibitors in patients with estrogen receptor–positive, HER2-negative breast cancers who also have PIK3CA activating mutations. In clinical trials, this strategy led to objective responses but not change outcomes.
The final tier is not Tier VI, as might be expected, but Tier X, with the X in this case being the unknown – that is, alterations/mutations for which there is neither preclinical nor clinical evidence to support their hypothetical use as a drug target.
“This clinical benefit–centered classification system offers a common language for all the actors involved in clinical cancer drug development. Its implementation in sequencing reports, tumor boards, and scientific communication can enable precise treatment decisions and facilitate discussions with patients about novel therapeutic options,” Dr. Mateo and his associates wrote in their conclusion.
The development process was supported by ESMO. Multiple coauthors reported financial relationships with various companies as well as grants/support from other foundations or charities.
The European Society for Medical Oncology (ESMO) has published a proposed scale that would rank molecular targets for various cancers by how well they can be treated with new or emerging drugs.
The ESMO Scale of Clinical Actionability for Molecular Targets is designed to “harmonize and standardize the reporting and interpretation of clinically relevant genomics data,” according to Joaquin Mateo, MD, PhD, from the Vall d’Hebron Institute of Oncology in Barcelona, Spain, and his fellow members of the ESMO Translational Research and Precision Medicine Working Group.
“A major challenge for oncologists in the clinic is to distinguish between findings that represent proven clinical value or potential value based on preliminary clinical or preclinical evidence from hypothetical gene-drug matches and findings that are currently irrelevant for clinical practice,” they wrote in Annals of Oncology.
The scale groups targets into one of six tiers based on levels of evidence ranging from the gold standard of prospective, randomized clinical trials to targets for which there are no evidence and only hypothetical actionability. The primary goal is to help oncologists assign priority to potential targets when they review results of gene-sequencing panels for individual patients, according to the developers.
Briefly, the six tiers are:
Tier I includes targets that are agreed to be suitable for routine use and a recommended specific drug when a specific molecular alteration is detected. Examples include trastuzumab for human epidermal growth factor receptor 2 (HER2)–positive breast cancer, and inhibitors of epidermal growth factor receptor (EGFR) in patients with non–small cell lung cancer positive for EGFR mutations.
Tier II includes “investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed.” This tier includes agents that work in the phosphatidylinostiol 3-kinase pathway.
Tier III is similar to Tier II, in that it includes investigational targets that define a patient population with proven benefit from a targeted therapy, but in this case the target is detected in a different tumor type that has not previously been studied. For example, the targeted agent vemurafenib (Zelboraf), which extends survival of patients with metastatic melanomas carrying the BRAF V600E mutation, has only limited activity against BRAF-mutated colorectal cancers.
Tier IV includes targets with preclinical evidence of actionability.
Tier V includes targets with “evidence of relevant antitumor activity, not resulting in clinical meaningful benefit as single treatment but supporting development of cotargeting approaches.” The authors cite the example of PIK3CA inhibitors in patients with estrogen receptor–positive, HER2-negative breast cancers who also have PIK3CA activating mutations. In clinical trials, this strategy led to objective responses but not change outcomes.
The final tier is not Tier VI, as might be expected, but Tier X, with the X in this case being the unknown – that is, alterations/mutations for which there is neither preclinical nor clinical evidence to support their hypothetical use as a drug target.
“This clinical benefit–centered classification system offers a common language for all the actors involved in clinical cancer drug development. Its implementation in sequencing reports, tumor boards, and scientific communication can enable precise treatment decisions and facilitate discussions with patients about novel therapeutic options,” Dr. Mateo and his associates wrote in their conclusion.
The development process was supported by ESMO. Multiple coauthors reported financial relationships with various companies as well as grants/support from other foundations or charities.
The European Society for Medical Oncology (ESMO) has published a proposed scale that would rank molecular targets for various cancers by how well they can be treated with new or emerging drugs.
The ESMO Scale of Clinical Actionability for Molecular Targets is designed to “harmonize and standardize the reporting and interpretation of clinically relevant genomics data,” according to Joaquin Mateo, MD, PhD, from the Vall d’Hebron Institute of Oncology in Barcelona, Spain, and his fellow members of the ESMO Translational Research and Precision Medicine Working Group.
“A major challenge for oncologists in the clinic is to distinguish between findings that represent proven clinical value or potential value based on preliminary clinical or preclinical evidence from hypothetical gene-drug matches and findings that are currently irrelevant for clinical practice,” they wrote in Annals of Oncology.
The scale groups targets into one of six tiers based on levels of evidence ranging from the gold standard of prospective, randomized clinical trials to targets for which there are no evidence and only hypothetical actionability. The primary goal is to help oncologists assign priority to potential targets when they review results of gene-sequencing panels for individual patients, according to the developers.
Briefly, the six tiers are:
Tier I includes targets that are agreed to be suitable for routine use and a recommended specific drug when a specific molecular alteration is detected. Examples include trastuzumab for human epidermal growth factor receptor 2 (HER2)–positive breast cancer, and inhibitors of epidermal growth factor receptor (EGFR) in patients with non–small cell lung cancer positive for EGFR mutations.
Tier II includes “investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed.” This tier includes agents that work in the phosphatidylinostiol 3-kinase pathway.
Tier III is similar to Tier II, in that it includes investigational targets that define a patient population with proven benefit from a targeted therapy, but in this case the target is detected in a different tumor type that has not previously been studied. For example, the targeted agent vemurafenib (Zelboraf), which extends survival of patients with metastatic melanomas carrying the BRAF V600E mutation, has only limited activity against BRAF-mutated colorectal cancers.
Tier IV includes targets with preclinical evidence of actionability.
Tier V includes targets with “evidence of relevant antitumor activity, not resulting in clinical meaningful benefit as single treatment but supporting development of cotargeting approaches.” The authors cite the example of PIK3CA inhibitors in patients with estrogen receptor–positive, HER2-negative breast cancers who also have PIK3CA activating mutations. In clinical trials, this strategy led to objective responses but not change outcomes.
The final tier is not Tier VI, as might be expected, but Tier X, with the X in this case being the unknown – that is, alterations/mutations for which there is neither preclinical nor clinical evidence to support their hypothetical use as a drug target.
“This clinical benefit–centered classification system offers a common language for all the actors involved in clinical cancer drug development. Its implementation in sequencing reports, tumor boards, and scientific communication can enable precise treatment decisions and facilitate discussions with patients about novel therapeutic options,” Dr. Mateo and his associates wrote in their conclusion.
The development process was supported by ESMO. Multiple coauthors reported financial relationships with various companies as well as grants/support from other foundations or charities.
Key clinical point: The scale is intended to standardize reporting and interpretation of cancer gene panel results to help oncologists plan treatment.
Major finding: The scale divides current and future therapeutic targets into tiers based on levels of clinical and preclinical evidence.
Study details: Proposed guiding principles for a classification system developed by the Translational Research and Precision Medicine Working Group of the European Society of Medical Oncology.
Disclosures: The development process was supported by ESMO. Multiple coauthors reported financial relationships with various companies as well as grants/support from other foundations or charities.
Source: Mateo J et al. Ann Oncol. 2018 Aug 21. doi: 10.1093/annonc/mdy263.
Disqus Comments
Default
Consolidated Pubs: Do Not Show Source Publication Logo
Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.
The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.
The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.
Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.
“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”
The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.
The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.
The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.
Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.
In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.
The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.
“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.
The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.
I strongly concur with the U.S. Preventive Services Task Force recommendation on early screening for syphilis infection in all pregnant women. There is benefit to screening all women for syphilis in early pregnancy given the risks of miscarriage, congenital syphilis, and maternal illness – if untreated. Additionally, in women who live in high prevalence areas or with high-risk behaviors for acquiring syphilis, testing should be performed again in the third trimester and at delivery. Also, all women with a fetal death after 20 weeks should be tested or retested if testing was done earlier in pregnancy.
Martina Badell, MD, is a maternal-fetal medicine specialist at Emory University and director of the Emory University Hospital Midtown Perinatal Center, both in Atlanta. Dr. Badell reported no relevant financial conflicts. She was asked to comment on the USPSTF recommendation.
I strongly concur with the U.S. Preventive Services Task Force recommendation on early screening for syphilis infection in all pregnant women. There is benefit to screening all women for syphilis in early pregnancy given the risks of miscarriage, congenital syphilis, and maternal illness – if untreated. Additionally, in women who live in high prevalence areas or with high-risk behaviors for acquiring syphilis, testing should be performed again in the third trimester and at delivery. Also, all women with a fetal death after 20 weeks should be tested or retested if testing was done earlier in pregnancy.
Martina Badell, MD, is a maternal-fetal medicine specialist at Emory University and director of the Emory University Hospital Midtown Perinatal Center, both in Atlanta. Dr. Badell reported no relevant financial conflicts. She was asked to comment on the USPSTF recommendation.
Body
I strongly concur with the U.S. Preventive Services Task Force recommendation on early screening for syphilis infection in all pregnant women. There is benefit to screening all women for syphilis in early pregnancy given the risks of miscarriage, congenital syphilis, and maternal illness – if untreated. Additionally, in women who live in high prevalence areas or with high-risk behaviors for acquiring syphilis, testing should be performed again in the third trimester and at delivery. Also, all women with a fetal death after 20 weeks should be tested or retested if testing was done earlier in pregnancy.
Martina Badell, MD, is a maternal-fetal medicine specialist at Emory University and director of the Emory University Hospital Midtown Perinatal Center, both in Atlanta. Dr. Badell reported no relevant financial conflicts. She was asked to comment on the USPSTF recommendation.
Title
Early syphilis screening benefits all pregnant women
Early syphilis screening benefits all pregnant women
Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.
The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.
The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.
Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.
“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”
The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.
The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.
The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.
Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.
In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.
The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.
“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.
The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.
Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.
The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.
The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.
Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.
“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”
The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.
The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.
The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.
Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.
In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.
The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.
“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.
The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.
An updated set of practice guidelines developed by the American Academy of Neurology recommends that patients with prolonged disorders of consciousness, such as a vegetative state or minimally conscious state, first undergo treatment for other outside symptoms and conditions to increase the likelihood of initial accurate diagnosis. The AAN also recommends that patients be evaluated by multidisciplinary specialists using standardized neurobehavioral assessments.
sudok1/thinkstock
“People are sometimes misdiagnosed due to underlying impairments that can mask awareness,” guidelines first author Joseph T. Giacino, PhD, of Harvard Medical School, Boston, and Spaulding Rehabilitation Hospital, Charlestown, Mass., stated in a press release about the guidelines. “An inaccurate diagnosis can lead to inappropriate care decisions and poor health outcomes. Misdiagnosis may result in premature or inappropriate treatment withdrawal, failure to recommend beneficial rehabilitative treatments, and worse outcome. That is why an early and accurate diagnosis is so important.”
The practice guidelines, published Aug. 8 in Neurology, update the 1995 recommendations from the AAN on persistent vegetative state (VS) as well as a 2002 case definition of minimally conscious state (MCS) developed by the AAN, American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research. In the new document, these same organizations made 18 recommendations about prolonged disorders of consciousness (DoC) based on three levels of evidence: Level A evidence was defined as the strongest recommendation, Level B evidence consisted of recommendations with a confident rationale and a “favorable benefit-risk profile,” and Level C evidence was the lowest level of recommendation that was still useful to clinical practice. Evidence was grouped into four different classifications based on the modified Grading of Recommendations Assessment, Development, and Evaluation process in a systematic review and based on “strong related evidence, established principles of care, and inferences.”
In the guidelines, the committee made the following recommendations:
Medically stable patients with DoC should be moved to multidisciplinary care settings where specialists can “optimize diagnostic evaluation, prognostication, and subsequent management, including effective medical monitoring and rehabilitative care” (Level B).
Patients should receive care for confounding conditions, receive serial standardized assessments, and undergo care that “optimizes arousal” to maximize initial accurate diagnoses (Level B).
Clinicians should communicate to families of patients with prolonged DoC that adult patients in an MCS caused by traumatic injury tend to have “more favorable outcomes,” compared with patients who are in a VS and patients with unresponsive wakefulness syndrome (UWS) caused by a nontraumatic injury (Level B).
Clinicians must discuss long-term care with families of patients with prolonged DoC and a poor prognosis (Level A), indicate that not all patients of this type have a poor prognosis, administer Coma Recovery Scale–Revised, and perform imaging, such as structural MRI and single-photon emission CT, to determine prognosis in these patients (Level B).
Regarding discussion of long-term care with families of children with prolonged DoC, clinicians should acknowledge that prognostic assessment, treatment, and natural history of recovery is not well-defined for children with prolonged DoC (Level B).
In patients with traumatic VS, UWS, or MCS, amantadine should be prescribed (100-200 mg) between 4 weeks and 16 weeks after injury to lower the risk of disability and increase the likelihood of functional recovery (Level B).
Clinicians should always assess and treat pain as well as discuss “evidence supporting treatment approaches” (Level B).
In addition, the subcommittee recommended changing the term permanent VS to chronic VS/UWS, citing Level B evidence. “Continued use of the term permanent VS is not justified. Use of this term implies irreversibility, which is not supported by the current research and has implications for family counseling, decision making, and the ethics of the field,” Dr. Giacino and his colleagues wrote.
In a separate summary of the guidelines, Dr. Giacino and his colleagues expressed concern about the lack of moderate or strong evidence for diagnostic assessment procedures in the literature, which they partially attributed to the inclusion of patients out 28 days or less from their injury in the systematic review for the guidelines. They further noted the lack of a gold-standard diagnostic approach for these patients, a lack of masking in diagnostic studies and tracking of recovery milestones and long-term functional outcomes for patients, and the limitations of the mainly retrospective analyses of outcomes in studies that they included. In addition, Dr. Giacino and his colleagues noted a lack of therapeutic studies with patients in inpatient rehabilitation centers and a “tendency by insurers to preferentially authorize rehabilitative care in lower-cost settings.” They excluded studies that had less than 20 patients, no control group, and were not “methodologically sound.”
Shorter lengths of stay in inpatient rehabilitation at academic medical centers have also led to problems in recruiting for placebo-controlled clinical trials, they noted.
“Under these circumstances, family members are often reticent to enroll patients with prolonged DoC in a placebo-controlled trial in view of the 50% likelihood of assignment to the placebo arm, preventing any possibility of active treatment during rehabilitation apart from routine physical, occupational, and speech therapies,” the authors wrote.
Several of the guidelines’ 16 authors disclosed ties to publishing houses and commercial or government entities, and participate in other activities related to the content of the published guidelines. Please see the full study for a complete list of disclosures.
Body
The American Academy of Neurology Guideline on Disorders of Consciousness should be lauded for its focus on rehabilitation of this population, but it misses an opportunity to address “the broader ethical implications for patient care and institutional reform,” Joseph J. Fins, MD, and James L. Bernat, MD, wrote in a related editorial.
The authors commended the guidelines for recommending a change in reclassifying permanent vegetative state (VS) as “chronic vegetative state” but noted that the designation may be too broad, considering it encompasses patients who were misdiagnosed, patients who improved after treatment, patients with cognitive-motor disassociation, and patients who have undergone late improvements to achieve some level of consciousness. Defining these patients to clarify their prognoses will be important in determining which patients with VS are able to make late improvements, they said.
“While this redesignation seems warranted on clinical and epidemiologic grounds, it will create repercussions beyond the house of medicine given that the right to refuse life-sustaining treatment initially was predicated upon the irreversibility of the VS,” the authors wrote.
Dr. Fins and Dr. Bernat also acknowledged the seemingly contradictory recommendation of systematizing the care of patients with prolonged disorders of consciousness given that the infrastructure to provide this care is unavailable and unaffordable for many patients.
“Now that the Guideline has stipulated benchmarks for practice, practitioners and institutions need to meet this standard of care, and payers must ensure that these services are covered. It is acceptable neither to plead ignorance of these conditions nor to assert that nothing can be done to help ameliorate the burden of severe brain injury,” the authors wrote. “Given the utility of greater specialized care in diagnosis, treatment, and rehabilitation, and the equal importance of avoiding medical complications that can impede recovery, our society must provide the infrastructure and resources needed to offer quality care.”
Dr. Fins is with the division of medical ethics and the Consortium for the Advanced Study of Brain Injury at Cornell University, New York. Dr. Bernat is with the departments of neurology and medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. They receive royalties from several published books that are relevant to the content of the guidelines.
The American Academy of Neurology Guideline on Disorders of Consciousness should be lauded for its focus on rehabilitation of this population, but it misses an opportunity to address “the broader ethical implications for patient care and institutional reform,” Joseph J. Fins, MD, and James L. Bernat, MD, wrote in a related editorial.
The authors commended the guidelines for recommending a change in reclassifying permanent vegetative state (VS) as “chronic vegetative state” but noted that the designation may be too broad, considering it encompasses patients who were misdiagnosed, patients who improved after treatment, patients with cognitive-motor disassociation, and patients who have undergone late improvements to achieve some level of consciousness. Defining these patients to clarify their prognoses will be important in determining which patients with VS are able to make late improvements, they said.
“While this redesignation seems warranted on clinical and epidemiologic grounds, it will create repercussions beyond the house of medicine given that the right to refuse life-sustaining treatment initially was predicated upon the irreversibility of the VS,” the authors wrote.
Dr. Fins and Dr. Bernat also acknowledged the seemingly contradictory recommendation of systematizing the care of patients with prolonged disorders of consciousness given that the infrastructure to provide this care is unavailable and unaffordable for many patients.
“Now that the Guideline has stipulated benchmarks for practice, practitioners and institutions need to meet this standard of care, and payers must ensure that these services are covered. It is acceptable neither to plead ignorance of these conditions nor to assert that nothing can be done to help ameliorate the burden of severe brain injury,” the authors wrote. “Given the utility of greater specialized care in diagnosis, treatment, and rehabilitation, and the equal importance of avoiding medical complications that can impede recovery, our society must provide the infrastructure and resources needed to offer quality care.”
Dr. Fins is with the division of medical ethics and the Consortium for the Advanced Study of Brain Injury at Cornell University, New York. Dr. Bernat is with the departments of neurology and medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. They receive royalties from several published books that are relevant to the content of the guidelines.
Body
The American Academy of Neurology Guideline on Disorders of Consciousness should be lauded for its focus on rehabilitation of this population, but it misses an opportunity to address “the broader ethical implications for patient care and institutional reform,” Joseph J. Fins, MD, and James L. Bernat, MD, wrote in a related editorial.
The authors commended the guidelines for recommending a change in reclassifying permanent vegetative state (VS) as “chronic vegetative state” but noted that the designation may be too broad, considering it encompasses patients who were misdiagnosed, patients who improved after treatment, patients with cognitive-motor disassociation, and patients who have undergone late improvements to achieve some level of consciousness. Defining these patients to clarify their prognoses will be important in determining which patients with VS are able to make late improvements, they said.
“While this redesignation seems warranted on clinical and epidemiologic grounds, it will create repercussions beyond the house of medicine given that the right to refuse life-sustaining treatment initially was predicated upon the irreversibility of the VS,” the authors wrote.
Dr. Fins and Dr. Bernat also acknowledged the seemingly contradictory recommendation of systematizing the care of patients with prolonged disorders of consciousness given that the infrastructure to provide this care is unavailable and unaffordable for many patients.
“Now that the Guideline has stipulated benchmarks for practice, practitioners and institutions need to meet this standard of care, and payers must ensure that these services are covered. It is acceptable neither to plead ignorance of these conditions nor to assert that nothing can be done to help ameliorate the burden of severe brain injury,” the authors wrote. “Given the utility of greater specialized care in diagnosis, treatment, and rehabilitation, and the equal importance of avoiding medical complications that can impede recovery, our society must provide the infrastructure and resources needed to offer quality care.”
Dr. Fins is with the division of medical ethics and the Consortium for the Advanced Study of Brain Injury at Cornell University, New York. Dr. Bernat is with the departments of neurology and medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. They receive royalties from several published books that are relevant to the content of the guidelines.
Title
Guidelines offer a new standard of care
Guidelines offer a new standard of care
An updated set of practice guidelines developed by the American Academy of Neurology recommends that patients with prolonged disorders of consciousness, such as a vegetative state or minimally conscious state, first undergo treatment for other outside symptoms and conditions to increase the likelihood of initial accurate diagnosis. The AAN also recommends that patients be evaluated by multidisciplinary specialists using standardized neurobehavioral assessments.
sudok1/thinkstock
“People are sometimes misdiagnosed due to underlying impairments that can mask awareness,” guidelines first author Joseph T. Giacino, PhD, of Harvard Medical School, Boston, and Spaulding Rehabilitation Hospital, Charlestown, Mass., stated in a press release about the guidelines. “An inaccurate diagnosis can lead to inappropriate care decisions and poor health outcomes. Misdiagnosis may result in premature or inappropriate treatment withdrawal, failure to recommend beneficial rehabilitative treatments, and worse outcome. That is why an early and accurate diagnosis is so important.”
The practice guidelines, published Aug. 8 in Neurology, update the 1995 recommendations from the AAN on persistent vegetative state (VS) as well as a 2002 case definition of minimally conscious state (MCS) developed by the AAN, American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research. In the new document, these same organizations made 18 recommendations about prolonged disorders of consciousness (DoC) based on three levels of evidence: Level A evidence was defined as the strongest recommendation, Level B evidence consisted of recommendations with a confident rationale and a “favorable benefit-risk profile,” and Level C evidence was the lowest level of recommendation that was still useful to clinical practice. Evidence was grouped into four different classifications based on the modified Grading of Recommendations Assessment, Development, and Evaluation process in a systematic review and based on “strong related evidence, established principles of care, and inferences.”
In the guidelines, the committee made the following recommendations:
Medically stable patients with DoC should be moved to multidisciplinary care settings where specialists can “optimize diagnostic evaluation, prognostication, and subsequent management, including effective medical monitoring and rehabilitative care” (Level B).
Patients should receive care for confounding conditions, receive serial standardized assessments, and undergo care that “optimizes arousal” to maximize initial accurate diagnoses (Level B).
Clinicians should communicate to families of patients with prolonged DoC that adult patients in an MCS caused by traumatic injury tend to have “more favorable outcomes,” compared with patients who are in a VS and patients with unresponsive wakefulness syndrome (UWS) caused by a nontraumatic injury (Level B).
Clinicians must discuss long-term care with families of patients with prolonged DoC and a poor prognosis (Level A), indicate that not all patients of this type have a poor prognosis, administer Coma Recovery Scale–Revised, and perform imaging, such as structural MRI and single-photon emission CT, to determine prognosis in these patients (Level B).
Regarding discussion of long-term care with families of children with prolonged DoC, clinicians should acknowledge that prognostic assessment, treatment, and natural history of recovery is not well-defined for children with prolonged DoC (Level B).
In patients with traumatic VS, UWS, or MCS, amantadine should be prescribed (100-200 mg) between 4 weeks and 16 weeks after injury to lower the risk of disability and increase the likelihood of functional recovery (Level B).
Clinicians should always assess and treat pain as well as discuss “evidence supporting treatment approaches” (Level B).
In addition, the subcommittee recommended changing the term permanent VS to chronic VS/UWS, citing Level B evidence. “Continued use of the term permanent VS is not justified. Use of this term implies irreversibility, which is not supported by the current research and has implications for family counseling, decision making, and the ethics of the field,” Dr. Giacino and his colleagues wrote.
In a separate summary of the guidelines, Dr. Giacino and his colleagues expressed concern about the lack of moderate or strong evidence for diagnostic assessment procedures in the literature, which they partially attributed to the inclusion of patients out 28 days or less from their injury in the systematic review for the guidelines. They further noted the lack of a gold-standard diagnostic approach for these patients, a lack of masking in diagnostic studies and tracking of recovery milestones and long-term functional outcomes for patients, and the limitations of the mainly retrospective analyses of outcomes in studies that they included. In addition, Dr. Giacino and his colleagues noted a lack of therapeutic studies with patients in inpatient rehabilitation centers and a “tendency by insurers to preferentially authorize rehabilitative care in lower-cost settings.” They excluded studies that had less than 20 patients, no control group, and were not “methodologically sound.”
Shorter lengths of stay in inpatient rehabilitation at academic medical centers have also led to problems in recruiting for placebo-controlled clinical trials, they noted.
“Under these circumstances, family members are often reticent to enroll patients with prolonged DoC in a placebo-controlled trial in view of the 50% likelihood of assignment to the placebo arm, preventing any possibility of active treatment during rehabilitation apart from routine physical, occupational, and speech therapies,” the authors wrote.
Several of the guidelines’ 16 authors disclosed ties to publishing houses and commercial or government entities, and participate in other activities related to the content of the published guidelines. Please see the full study for a complete list of disclosures.
An updated set of practice guidelines developed by the American Academy of Neurology recommends that patients with prolonged disorders of consciousness, such as a vegetative state or minimally conscious state, first undergo treatment for other outside symptoms and conditions to increase the likelihood of initial accurate diagnosis. The AAN also recommends that patients be evaluated by multidisciplinary specialists using standardized neurobehavioral assessments.
sudok1/thinkstock
“People are sometimes misdiagnosed due to underlying impairments that can mask awareness,” guidelines first author Joseph T. Giacino, PhD, of Harvard Medical School, Boston, and Spaulding Rehabilitation Hospital, Charlestown, Mass., stated in a press release about the guidelines. “An inaccurate diagnosis can lead to inappropriate care decisions and poor health outcomes. Misdiagnosis may result in premature or inappropriate treatment withdrawal, failure to recommend beneficial rehabilitative treatments, and worse outcome. That is why an early and accurate diagnosis is so important.”
The practice guidelines, published Aug. 8 in Neurology, update the 1995 recommendations from the AAN on persistent vegetative state (VS) as well as a 2002 case definition of minimally conscious state (MCS) developed by the AAN, American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research. In the new document, these same organizations made 18 recommendations about prolonged disorders of consciousness (DoC) based on three levels of evidence: Level A evidence was defined as the strongest recommendation, Level B evidence consisted of recommendations with a confident rationale and a “favorable benefit-risk profile,” and Level C evidence was the lowest level of recommendation that was still useful to clinical practice. Evidence was grouped into four different classifications based on the modified Grading of Recommendations Assessment, Development, and Evaluation process in a systematic review and based on “strong related evidence, established principles of care, and inferences.”
In the guidelines, the committee made the following recommendations:
Medically stable patients with DoC should be moved to multidisciplinary care settings where specialists can “optimize diagnostic evaluation, prognostication, and subsequent management, including effective medical monitoring and rehabilitative care” (Level B).
Patients should receive care for confounding conditions, receive serial standardized assessments, and undergo care that “optimizes arousal” to maximize initial accurate diagnoses (Level B).
Clinicians should communicate to families of patients with prolonged DoC that adult patients in an MCS caused by traumatic injury tend to have “more favorable outcomes,” compared with patients who are in a VS and patients with unresponsive wakefulness syndrome (UWS) caused by a nontraumatic injury (Level B).
Clinicians must discuss long-term care with families of patients with prolonged DoC and a poor prognosis (Level A), indicate that not all patients of this type have a poor prognosis, administer Coma Recovery Scale–Revised, and perform imaging, such as structural MRI and single-photon emission CT, to determine prognosis in these patients (Level B).
Regarding discussion of long-term care with families of children with prolonged DoC, clinicians should acknowledge that prognostic assessment, treatment, and natural history of recovery is not well-defined for children with prolonged DoC (Level B).
In patients with traumatic VS, UWS, or MCS, amantadine should be prescribed (100-200 mg) between 4 weeks and 16 weeks after injury to lower the risk of disability and increase the likelihood of functional recovery (Level B).
Clinicians should always assess and treat pain as well as discuss “evidence supporting treatment approaches” (Level B).
In addition, the subcommittee recommended changing the term permanent VS to chronic VS/UWS, citing Level B evidence. “Continued use of the term permanent VS is not justified. Use of this term implies irreversibility, which is not supported by the current research and has implications for family counseling, decision making, and the ethics of the field,” Dr. Giacino and his colleagues wrote.
In a separate summary of the guidelines, Dr. Giacino and his colleagues expressed concern about the lack of moderate or strong evidence for diagnostic assessment procedures in the literature, which they partially attributed to the inclusion of patients out 28 days or less from their injury in the systematic review for the guidelines. They further noted the lack of a gold-standard diagnostic approach for these patients, a lack of masking in diagnostic studies and tracking of recovery milestones and long-term functional outcomes for patients, and the limitations of the mainly retrospective analyses of outcomes in studies that they included. In addition, Dr. Giacino and his colleagues noted a lack of therapeutic studies with patients in inpatient rehabilitation centers and a “tendency by insurers to preferentially authorize rehabilitative care in lower-cost settings.” They excluded studies that had less than 20 patients, no control group, and were not “methodologically sound.”
Shorter lengths of stay in inpatient rehabilitation at academic medical centers have also led to problems in recruiting for placebo-controlled clinical trials, they noted.
“Under these circumstances, family members are often reticent to enroll patients with prolonged DoC in a placebo-controlled trial in view of the 50% likelihood of assignment to the placebo arm, preventing any possibility of active treatment during rehabilitation apart from routine physical, occupational, and speech therapies,” the authors wrote.
Several of the guidelines’ 16 authors disclosed ties to publishing houses and commercial or government entities, and participate in other activities related to the content of the published guidelines. Please see the full study for a complete list of disclosures.
An update to the first-ever guideline on adult congenital heart disease, released today, provides new recommendations and a more nuanced classification system based on data and expertise accrued in the field over the past decade.
Dr. Curt J Daniels
Recommendations for more than two dozen specific lesion types are included in the 2018 American Heart Association/American College of Cardiology Guideline for the Management of Adults With Congenital Heart Disease.
The 172-page document, published online in the Journal of the American College of Cardiology and Circulation, also includes recommendations on general principles ranging from evaluation of suspected disease to palliative care and end-of-life issues.
“The original guidelines, I think everyone would agree, were just a lot more best practice and expert consensus, whereas now we have at least some data to support our recommendations,” said guideline-writing committee vice chair Curt J. Daniels, MD.
Better road map
The document is intended to provide a “better road map” for all providers who will see such patients in their practice, said Dr. Daniels, director of the adult congenital heart disease and pulmonary hypertension program at Ohio State University Heart Center and Nationwide Children’s Hospital, Columbus.
“There are not enough adult congenital heart disease cardiologists and programs in the country to care for the almost 1.5 million adults with congenital heart disease in the United States, so we know these patients are cared for by general cardiologists,” Dr. Daniels said in an interview. “Having some guidelines about when to refer to those patients was a huge part of the purpose of these updated guidelines.”
The revamped classification system underlying the new guidelines seeks to better characterize disease severity based on the complexity of its anatomy and physiology, according to Dr. Daniels.
Previous documents, including the original 2008 AHA/ACC guideline (Circulation. 2008 Nov 7;118:e714-833), focused mainly on anatomic classifications to rank severity, he said.
“Traditionally, we’ve based the severity of congenital heart disease based on the complexity of anatomy they were born with, but that goes only so far,” Dr. Daniels said in an interview.
More than just anatomy
Dr. Robert Jaquiss
In the new system, anatomy is classified as simple (I, e.g., isolated small atrial septal defect), moderately complex (II, e.g., coarctation of the aorta), or greatly complex (III, e.g., cyanotic congenital heart defect), while physiologic stages range from A to D, increasing along with the severity of physiologic variables such as New York Heart Association functional class; exercise capacity; aortic enlargement; arrhythmias; renal, hepatic, or pulmonary function; and venal or arterial stenosis.
A normotensive patient with repaired coarctation of the aorta would be classified as IIA if she had normal end-organ function and exercise capacity, whereas a similar patient with an ascending aortic diameter of 4.0 cm would be classified as IIB, and with the addition of moderate aortic stenosis, would be classified as IIIC, according to an example provided in the guidelines.
Congenital heart disease specialist Robert “Jake” Jaquiss, MD, said in an interview that consideration of physiology alongside anatomy is one of the most important features of the new guidelines.
“This is a way of thinking about patients that involves not just their anatomy, but also considering a variety of domains in which there may be physiologic dysfunction that can modify the underlying anatomy,” said Dr. Jaquiss, chief of pediatric and congenital heart surgery at Children’s Medical Center/University of Texas Southwestern Medical Center, Dallas. “I think that is a more clinically relevant way to think about patients and patient evaluation management, and I commend the authors for that focus.”
For example, one patient who has undergone a Fontan procedure may be fully functional, whereas another with nearly identical anatomy may be burdened by arrhythmias, fluid retention, and impaired exercise function. “If we don’t grasp the physiologic difference, we treat the two patients the same way, which is obviously inappropriate,” Dr. Jaquiss said.
Research directions
Much more research needs to be done, according to guideline authors, who list 60 unresolved research questions that represent evidence gaps and future directions for study.
For example, outstanding questions related to tetralogy of Fallot focus on the optimal timing for pulmonary valve replacement, the role of pulmonary valve replacement and ventricular tachycardia ablation in decreasing sudden cardiac death risk, and whether implantable cardioverter-defibrillators reduce mortality.
“These are the kinds of evolutionary sort of understandings and alterations in the intervention, both at the original operation and for assessment of care, and what we think about it and how we think about it in 2018 is quite different than how we thought in 2008, and I dare say it’ll be even more different in 2028,” Dr. Jaquiss said.
The AHA/ACC guideline was developed in association with the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
Dr. Daniels reported a relevant relationship with Actelion. Guideline coauthors reported relevant relationships in that same category with Actelion, Boehringer Ingelheim, Cormatrix, Edward Lifesciences, Gilead, Medtronic, Novartis, Sorin (LivaNova), St. Jude Medical, and United Therapeutics. No other disclosures were reported.
An update to the first-ever guideline on adult congenital heart disease, released today, provides new recommendations and a more nuanced classification system based on data and expertise accrued in the field over the past decade.
Dr. Curt J Daniels
Recommendations for more than two dozen specific lesion types are included in the 2018 American Heart Association/American College of Cardiology Guideline for the Management of Adults With Congenital Heart Disease.
The 172-page document, published online in the Journal of the American College of Cardiology and Circulation, also includes recommendations on general principles ranging from evaluation of suspected disease to palliative care and end-of-life issues.
“The original guidelines, I think everyone would agree, were just a lot more best practice and expert consensus, whereas now we have at least some data to support our recommendations,” said guideline-writing committee vice chair Curt J. Daniels, MD.
Better road map
The document is intended to provide a “better road map” for all providers who will see such patients in their practice, said Dr. Daniels, director of the adult congenital heart disease and pulmonary hypertension program at Ohio State University Heart Center and Nationwide Children’s Hospital, Columbus.
“There are not enough adult congenital heart disease cardiologists and programs in the country to care for the almost 1.5 million adults with congenital heart disease in the United States, so we know these patients are cared for by general cardiologists,” Dr. Daniels said in an interview. “Having some guidelines about when to refer to those patients was a huge part of the purpose of these updated guidelines.”
The revamped classification system underlying the new guidelines seeks to better characterize disease severity based on the complexity of its anatomy and physiology, according to Dr. Daniels.
Previous documents, including the original 2008 AHA/ACC guideline (Circulation. 2008 Nov 7;118:e714-833), focused mainly on anatomic classifications to rank severity, he said.
“Traditionally, we’ve based the severity of congenital heart disease based on the complexity of anatomy they were born with, but that goes only so far,” Dr. Daniels said in an interview.
More than just anatomy
Dr. Robert Jaquiss
In the new system, anatomy is classified as simple (I, e.g., isolated small atrial septal defect), moderately complex (II, e.g., coarctation of the aorta), or greatly complex (III, e.g., cyanotic congenital heart defect), while physiologic stages range from A to D, increasing along with the severity of physiologic variables such as New York Heart Association functional class; exercise capacity; aortic enlargement; arrhythmias; renal, hepatic, or pulmonary function; and venal or arterial stenosis.
A normotensive patient with repaired coarctation of the aorta would be classified as IIA if she had normal end-organ function and exercise capacity, whereas a similar patient with an ascending aortic diameter of 4.0 cm would be classified as IIB, and with the addition of moderate aortic stenosis, would be classified as IIIC, according to an example provided in the guidelines.
Congenital heart disease specialist Robert “Jake” Jaquiss, MD, said in an interview that consideration of physiology alongside anatomy is one of the most important features of the new guidelines.
“This is a way of thinking about patients that involves not just their anatomy, but also considering a variety of domains in which there may be physiologic dysfunction that can modify the underlying anatomy,” said Dr. Jaquiss, chief of pediatric and congenital heart surgery at Children’s Medical Center/University of Texas Southwestern Medical Center, Dallas. “I think that is a more clinically relevant way to think about patients and patient evaluation management, and I commend the authors for that focus.”
For example, one patient who has undergone a Fontan procedure may be fully functional, whereas another with nearly identical anatomy may be burdened by arrhythmias, fluid retention, and impaired exercise function. “If we don’t grasp the physiologic difference, we treat the two patients the same way, which is obviously inappropriate,” Dr. Jaquiss said.
Research directions
Much more research needs to be done, according to guideline authors, who list 60 unresolved research questions that represent evidence gaps and future directions for study.
For example, outstanding questions related to tetralogy of Fallot focus on the optimal timing for pulmonary valve replacement, the role of pulmonary valve replacement and ventricular tachycardia ablation in decreasing sudden cardiac death risk, and whether implantable cardioverter-defibrillators reduce mortality.
“These are the kinds of evolutionary sort of understandings and alterations in the intervention, both at the original operation and for assessment of care, and what we think about it and how we think about it in 2018 is quite different than how we thought in 2008, and I dare say it’ll be even more different in 2028,” Dr. Jaquiss said.
The AHA/ACC guideline was developed in association with the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
Dr. Daniels reported a relevant relationship with Actelion. Guideline coauthors reported relevant relationships in that same category with Actelion, Boehringer Ingelheim, Cormatrix, Edward Lifesciences, Gilead, Medtronic, Novartis, Sorin (LivaNova), St. Jude Medical, and United Therapeutics. No other disclosures were reported.
An update to the first-ever guideline on adult congenital heart disease, released today, provides new recommendations and a more nuanced classification system based on data and expertise accrued in the field over the past decade.
Dr. Curt J Daniels
Recommendations for more than two dozen specific lesion types are included in the 2018 American Heart Association/American College of Cardiology Guideline for the Management of Adults With Congenital Heart Disease.
The 172-page document, published online in the Journal of the American College of Cardiology and Circulation, also includes recommendations on general principles ranging from evaluation of suspected disease to palliative care and end-of-life issues.
“The original guidelines, I think everyone would agree, were just a lot more best practice and expert consensus, whereas now we have at least some data to support our recommendations,” said guideline-writing committee vice chair Curt J. Daniels, MD.
Better road map
The document is intended to provide a “better road map” for all providers who will see such patients in their practice, said Dr. Daniels, director of the adult congenital heart disease and pulmonary hypertension program at Ohio State University Heart Center and Nationwide Children’s Hospital, Columbus.
“There are not enough adult congenital heart disease cardiologists and programs in the country to care for the almost 1.5 million adults with congenital heart disease in the United States, so we know these patients are cared for by general cardiologists,” Dr. Daniels said in an interview. “Having some guidelines about when to refer to those patients was a huge part of the purpose of these updated guidelines.”
The revamped classification system underlying the new guidelines seeks to better characterize disease severity based on the complexity of its anatomy and physiology, according to Dr. Daniels.
Previous documents, including the original 2008 AHA/ACC guideline (Circulation. 2008 Nov 7;118:e714-833), focused mainly on anatomic classifications to rank severity, he said.
“Traditionally, we’ve based the severity of congenital heart disease based on the complexity of anatomy they were born with, but that goes only so far,” Dr. Daniels said in an interview.
More than just anatomy
Dr. Robert Jaquiss
In the new system, anatomy is classified as simple (I, e.g., isolated small atrial septal defect), moderately complex (II, e.g., coarctation of the aorta), or greatly complex (III, e.g., cyanotic congenital heart defect), while physiologic stages range from A to D, increasing along with the severity of physiologic variables such as New York Heart Association functional class; exercise capacity; aortic enlargement; arrhythmias; renal, hepatic, or pulmonary function; and venal or arterial stenosis.
A normotensive patient with repaired coarctation of the aorta would be classified as IIA if she had normal end-organ function and exercise capacity, whereas a similar patient with an ascending aortic diameter of 4.0 cm would be classified as IIB, and with the addition of moderate aortic stenosis, would be classified as IIIC, according to an example provided in the guidelines.
Congenital heart disease specialist Robert “Jake” Jaquiss, MD, said in an interview that consideration of physiology alongside anatomy is one of the most important features of the new guidelines.
“This is a way of thinking about patients that involves not just their anatomy, but also considering a variety of domains in which there may be physiologic dysfunction that can modify the underlying anatomy,” said Dr. Jaquiss, chief of pediatric and congenital heart surgery at Children’s Medical Center/University of Texas Southwestern Medical Center, Dallas. “I think that is a more clinically relevant way to think about patients and patient evaluation management, and I commend the authors for that focus.”
For example, one patient who has undergone a Fontan procedure may be fully functional, whereas another with nearly identical anatomy may be burdened by arrhythmias, fluid retention, and impaired exercise function. “If we don’t grasp the physiologic difference, we treat the two patients the same way, which is obviously inappropriate,” Dr. Jaquiss said.
Research directions
Much more research needs to be done, according to guideline authors, who list 60 unresolved research questions that represent evidence gaps and future directions for study.
For example, outstanding questions related to tetralogy of Fallot focus on the optimal timing for pulmonary valve replacement, the role of pulmonary valve replacement and ventricular tachycardia ablation in decreasing sudden cardiac death risk, and whether implantable cardioverter-defibrillators reduce mortality.
“These are the kinds of evolutionary sort of understandings and alterations in the intervention, both at the original operation and for assessment of care, and what we think about it and how we think about it in 2018 is quite different than how we thought in 2008, and I dare say it’ll be even more different in 2028,” Dr. Jaquiss said.
The AHA/ACC guideline was developed in association with the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
Dr. Daniels reported a relevant relationship with Actelion. Guideline coauthors reported relevant relationships in that same category with Actelion, Boehringer Ingelheim, Cormatrix, Edward Lifesciences, Gilead, Medtronic, Novartis, Sorin (LivaNova), St. Jude Medical, and United Therapeutics. No other disclosures were reported.
The National Comprehensive Cancer Network (NCCN) has issued its first-ever clinical practice guidelines for the treatment of gestational trophoblastic neoplasia (GTN), a rare, serious complication of pregnancy that can often be cured, but can have devastating consequences if mismanaged or if treatment is needlessly delayed.
David Mutch, MD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, who heads the NCCN Clinical Practice Guidelines in Oncology Committee for GTN, explained the critical importance of the GTN guidelines.
“It’s a rare disease, people weren’t that familiar with it, and they often are patients treated with single-agent therapy when they should be treated with multi-agent therapy,” he said in an interview.
“There wasn’t a clear understanding of what to do except by those people who treated these patients regularly. The only thing most people knew was that it was very chemosensitive and should be curable, but it’s only curable if you follow the appropriate algorithms,” he continued.
The algorithms he referred to were established by a handful of centers with expertise and experience in diagnosing and treating these rare conditions, including noninvasive hydatidiform mole, invasive mole, and choriocarcinoma, the most aggressive form of GTN.
Neil Horowitz, MD, director of clinical research in gynecologic oncology at the Dana-Farber Cancer Institute in Boston, works with colleagues in one of those referral centers, the New England Trophoblastic Disease Center, and is familiar with the new guidelines. As with other rare malignancies, there are data to suggest that patients with GTN who are treated in centers of excellence with higher patient volumes have better outcomes than do similar patients treated in a community setting, he said in an interview.
Placental origins
GTNs arise from placental rather than maternal tissue. They most commonly present with vaginal bleeding and a rapidly enlarging uterus, and may be accompanied by pelvic pain or pressure, anemia, severe nausea/vomiting (hyperemesis gravidarum), hyperthyroidism, or early-pregnancy preeclampsia.
The overall reported incidence of GTN in the United States, including hydatidiform mole, is approximately 110 to 120 per 100,000 pregnancies, and the reported incidence of choriocarcinoma is about 2 to 7 per 100,000, according to the National Cancer Institute.
The GTN guidelines provide evidence-based recommendations about optimal approaches to GTN in all of its known forms. For example, the section on noninvasive hydatidiform mole recommends the tests that should be routinely performed during workup, followed by surgery with either suction, dilation and curettage – preferably under ultrasound guidance – or hysterectomy for women who are older or who do not wish to preserve fertility.
The guidelines also specify steps that should be taken for diagnosis and staging of GTN as well as risk-based therapeutic approaches.
For example, the guidelines recommend therapy with either methotrexate alone or alternating with leucovorin, or dactinomycin alone for patients with confirmed low risk GTN, defined as a prognostic score less than 7.
The prognostic scoring index, also included in the guidelines, considers risk factors such as age, prior pregnancies, interval from an index pregnancy, pretreatment human chorionic gonadotropin (hCG) levels, site and number of metastases, largest tumor size, and previous chemotherapy failure.
For patients with high-risk GTN, defined as FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stages II-III with a prognostic score of 7 or greater, or FIGO stage IV, chemotherapy with the EMA/CO regimen is recommended. This aggressive regimen consists of etoposide, methotrexate, dactinomycin (the “EMA “component) plus cyclophosphamide and vincristine (the “CO” component).
“In my mind, the most important part of the guidelines is reiterating how the diagnosis of GTN should be made, and importantly, how the score should be calculated so that women are put in the appropriate low-risk or high-risk category, so they get the right treatment,” Dr. Horowitz said.
Reassuring insurers
Dr. Mutch said that he and his colleagues in GTN centers sometimes treat patients with intermediate or high-risk disease who were started on single-agent therapy or suboptimal therapies and present with advanced, drug-resistant disease.
“These guidelines were established so that people could see exactly what needs to be done when,” he said.
The guidelines also are critical for convincing third-party payers about the need for specific treatments, he added.
“I had a high-risk patient who needed EMA/CO, and the insurance company said ‘well, there’s no NCCN guidelines – we won’t approve it.’ So then I had to wait 3 days while it went through peer review. Meanwhile, the tumor doubled in size, and then the nurse who was reviewing it declined the ‘CO’ part, so that was delayed a week, and it really jeopardized this patient’s survival,” Dr. Mutch said.
The guidelines also include recommendations for patients with special clinical situations, such as women with clinical responses to EMA/CO who continue to have plateauing low levels of hCG or have a re-elevation of hCG levels after having a complete response to EMA/CO.
There are also specific recommendations for treatment of two even rarer intermediate trophoblastic tumor types: placental-site trophoblastic tumor and epithelioid trophoblastic tumor.
The guidelines are supported by the NCCN. Dr. Mutch reported consulting/advisory board participation for Clovis. Dr. Horowitz reported having no relationships to disclose.
SOURCE: Gestational Trophoblastic Neoplasia. NCCN.org, Version 1.2019, published Aug. 9, 2018.
The National Comprehensive Cancer Network (NCCN) has issued its first-ever clinical practice guidelines for the treatment of gestational trophoblastic neoplasia (GTN), a rare, serious complication of pregnancy that can often be cured, but can have devastating consequences if mismanaged or if treatment is needlessly delayed.
David Mutch, MD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, who heads the NCCN Clinical Practice Guidelines in Oncology Committee for GTN, explained the critical importance of the GTN guidelines.
“It’s a rare disease, people weren’t that familiar with it, and they often are patients treated with single-agent therapy when they should be treated with multi-agent therapy,” he said in an interview.
“There wasn’t a clear understanding of what to do except by those people who treated these patients regularly. The only thing most people knew was that it was very chemosensitive and should be curable, but it’s only curable if you follow the appropriate algorithms,” he continued.
The algorithms he referred to were established by a handful of centers with expertise and experience in diagnosing and treating these rare conditions, including noninvasive hydatidiform mole, invasive mole, and choriocarcinoma, the most aggressive form of GTN.
Neil Horowitz, MD, director of clinical research in gynecologic oncology at the Dana-Farber Cancer Institute in Boston, works with colleagues in one of those referral centers, the New England Trophoblastic Disease Center, and is familiar with the new guidelines. As with other rare malignancies, there are data to suggest that patients with GTN who are treated in centers of excellence with higher patient volumes have better outcomes than do similar patients treated in a community setting, he said in an interview.
Placental origins
GTNs arise from placental rather than maternal tissue. They most commonly present with vaginal bleeding and a rapidly enlarging uterus, and may be accompanied by pelvic pain or pressure, anemia, severe nausea/vomiting (hyperemesis gravidarum), hyperthyroidism, or early-pregnancy preeclampsia.
The overall reported incidence of GTN in the United States, including hydatidiform mole, is approximately 110 to 120 per 100,000 pregnancies, and the reported incidence of choriocarcinoma is about 2 to 7 per 100,000, according to the National Cancer Institute.
The GTN guidelines provide evidence-based recommendations about optimal approaches to GTN in all of its known forms. For example, the section on noninvasive hydatidiform mole recommends the tests that should be routinely performed during workup, followed by surgery with either suction, dilation and curettage – preferably under ultrasound guidance – or hysterectomy for women who are older or who do not wish to preserve fertility.
The guidelines also specify steps that should be taken for diagnosis and staging of GTN as well as risk-based therapeutic approaches.
For example, the guidelines recommend therapy with either methotrexate alone or alternating with leucovorin, or dactinomycin alone for patients with confirmed low risk GTN, defined as a prognostic score less than 7.
The prognostic scoring index, also included in the guidelines, considers risk factors such as age, prior pregnancies, interval from an index pregnancy, pretreatment human chorionic gonadotropin (hCG) levels, site and number of metastases, largest tumor size, and previous chemotherapy failure.
For patients with high-risk GTN, defined as FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stages II-III with a prognostic score of 7 or greater, or FIGO stage IV, chemotherapy with the EMA/CO regimen is recommended. This aggressive regimen consists of etoposide, methotrexate, dactinomycin (the “EMA “component) plus cyclophosphamide and vincristine (the “CO” component).
“In my mind, the most important part of the guidelines is reiterating how the diagnosis of GTN should be made, and importantly, how the score should be calculated so that women are put in the appropriate low-risk or high-risk category, so they get the right treatment,” Dr. Horowitz said.
Reassuring insurers
Dr. Mutch said that he and his colleagues in GTN centers sometimes treat patients with intermediate or high-risk disease who were started on single-agent therapy or suboptimal therapies and present with advanced, drug-resistant disease.
“These guidelines were established so that people could see exactly what needs to be done when,” he said.
The guidelines also are critical for convincing third-party payers about the need for specific treatments, he added.
“I had a high-risk patient who needed EMA/CO, and the insurance company said ‘well, there’s no NCCN guidelines – we won’t approve it.’ So then I had to wait 3 days while it went through peer review. Meanwhile, the tumor doubled in size, and then the nurse who was reviewing it declined the ‘CO’ part, so that was delayed a week, and it really jeopardized this patient’s survival,” Dr. Mutch said.
The guidelines also include recommendations for patients with special clinical situations, such as women with clinical responses to EMA/CO who continue to have plateauing low levels of hCG or have a re-elevation of hCG levels after having a complete response to EMA/CO.
There are also specific recommendations for treatment of two even rarer intermediate trophoblastic tumor types: placental-site trophoblastic tumor and epithelioid trophoblastic tumor.
The guidelines are supported by the NCCN. Dr. Mutch reported consulting/advisory board participation for Clovis. Dr. Horowitz reported having no relationships to disclose.
SOURCE: Gestational Trophoblastic Neoplasia. NCCN.org, Version 1.2019, published Aug. 9, 2018.
The National Comprehensive Cancer Network (NCCN) has issued its first-ever clinical practice guidelines for the treatment of gestational trophoblastic neoplasia (GTN), a rare, serious complication of pregnancy that can often be cured, but can have devastating consequences if mismanaged or if treatment is needlessly delayed.
David Mutch, MD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, who heads the NCCN Clinical Practice Guidelines in Oncology Committee for GTN, explained the critical importance of the GTN guidelines.
“It’s a rare disease, people weren’t that familiar with it, and they often are patients treated with single-agent therapy when they should be treated with multi-agent therapy,” he said in an interview.
“There wasn’t a clear understanding of what to do except by those people who treated these patients regularly. The only thing most people knew was that it was very chemosensitive and should be curable, but it’s only curable if you follow the appropriate algorithms,” he continued.
The algorithms he referred to were established by a handful of centers with expertise and experience in diagnosing and treating these rare conditions, including noninvasive hydatidiform mole, invasive mole, and choriocarcinoma, the most aggressive form of GTN.
Neil Horowitz, MD, director of clinical research in gynecologic oncology at the Dana-Farber Cancer Institute in Boston, works with colleagues in one of those referral centers, the New England Trophoblastic Disease Center, and is familiar with the new guidelines. As with other rare malignancies, there are data to suggest that patients with GTN who are treated in centers of excellence with higher patient volumes have better outcomes than do similar patients treated in a community setting, he said in an interview.
Placental origins
GTNs arise from placental rather than maternal tissue. They most commonly present with vaginal bleeding and a rapidly enlarging uterus, and may be accompanied by pelvic pain or pressure, anemia, severe nausea/vomiting (hyperemesis gravidarum), hyperthyroidism, or early-pregnancy preeclampsia.
The overall reported incidence of GTN in the United States, including hydatidiform mole, is approximately 110 to 120 per 100,000 pregnancies, and the reported incidence of choriocarcinoma is about 2 to 7 per 100,000, according to the National Cancer Institute.
The GTN guidelines provide evidence-based recommendations about optimal approaches to GTN in all of its known forms. For example, the section on noninvasive hydatidiform mole recommends the tests that should be routinely performed during workup, followed by surgery with either suction, dilation and curettage – preferably under ultrasound guidance – or hysterectomy for women who are older or who do not wish to preserve fertility.
The guidelines also specify steps that should be taken for diagnosis and staging of GTN as well as risk-based therapeutic approaches.
For example, the guidelines recommend therapy with either methotrexate alone or alternating with leucovorin, or dactinomycin alone for patients with confirmed low risk GTN, defined as a prognostic score less than 7.
The prognostic scoring index, also included in the guidelines, considers risk factors such as age, prior pregnancies, interval from an index pregnancy, pretreatment human chorionic gonadotropin (hCG) levels, site and number of metastases, largest tumor size, and previous chemotherapy failure.
For patients with high-risk GTN, defined as FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stages II-III with a prognostic score of 7 or greater, or FIGO stage IV, chemotherapy with the EMA/CO regimen is recommended. This aggressive regimen consists of etoposide, methotrexate, dactinomycin (the “EMA “component) plus cyclophosphamide and vincristine (the “CO” component).
“In my mind, the most important part of the guidelines is reiterating how the diagnosis of GTN should be made, and importantly, how the score should be calculated so that women are put in the appropriate low-risk or high-risk category, so they get the right treatment,” Dr. Horowitz said.
Reassuring insurers
Dr. Mutch said that he and his colleagues in GTN centers sometimes treat patients with intermediate or high-risk disease who were started on single-agent therapy or suboptimal therapies and present with advanced, drug-resistant disease.
“These guidelines were established so that people could see exactly what needs to be done when,” he said.
The guidelines also are critical for convincing third-party payers about the need for specific treatments, he added.
“I had a high-risk patient who needed EMA/CO, and the insurance company said ‘well, there’s no NCCN guidelines – we won’t approve it.’ So then I had to wait 3 days while it went through peer review. Meanwhile, the tumor doubled in size, and then the nurse who was reviewing it declined the ‘CO’ part, so that was delayed a week, and it really jeopardized this patient’s survival,” Dr. Mutch said.
The guidelines also include recommendations for patients with special clinical situations, such as women with clinical responses to EMA/CO who continue to have plateauing low levels of hCG or have a re-elevation of hCG levels after having a complete response to EMA/CO.
There are also specific recommendations for treatment of two even rarer intermediate trophoblastic tumor types: placental-site trophoblastic tumor and epithelioid trophoblastic tumor.
The guidelines are supported by the NCCN. Dr. Mutch reported consulting/advisory board participation for Clovis. Dr. Horowitz reported having no relationships to disclose.
SOURCE: Gestational Trophoblastic Neoplasia. NCCN.org, Version 1.2019, published Aug. 9, 2018.
Key clinical point: Gestational trophoblastic neoplasia (GTN) is a complication of pregnancy involving rare placental derived tumors that are generally curable with appropriate therapy, best delivered at a center of excellence.
Major finding: National Comprehensive Cancer Network Guidelines specify risk-based therapy for GTN based on staging and prognostic indicators.
Study details: Evidence-based guidelines issued by the National Comprehensive Cancer Network.
Disclosures: The guidelines are supported by the NCCN. Dr. Mutch reported consulting/advisory board participation for Clovis. Dr. Horowitz reported having no disclosures to report.
Source: Gestational Trophoblastic Neoplasia. NCCN.org, Version 1.2019, published Aug. 9, 2018.
Disqus Comments
Default
Consolidated Pubs: Do Not Show Source Publication Logo
