User login
Childhood trauma tied to increased Parkinson’s disease severity
new research shows.
Results of the first study to evaluate the relationship between childhood trauma and PD investigators found that the relationship appears to be dose dependent. Patients with PD who reported more than one ACE all experienced a statistically significant decrease in QOL, and for each additional ACE, there was significant worsening of motor symptoms.
This study supports a recent-call to-action paper in JAMA Neurology encouraging adoption of “trauma-informed neurology,” study investigator Indu Subramanian, MD, clinical professor, department of neurology, University of California, Los Angeles, said in an interview.
“We need to start asking about ACEs in everyone. It should be part of our medical intake,” said Dr. Subramanian, who is also the director of the Southwest Parkinson’s Disease Research, Education, and Clinical Center, West Los Angeles Veterans Affairs Medical Center.
The study was published online in Neurology: Clinical Practice.
Hard on the mind and body
A robust body of literature has clearly established a connection between ACEs, which include physical and emotional abuse, neglect, and household dysfunction, and negative physical health outcomes across the lifespan. These include stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature death as well as psychosocial health outcomes such as anxiety, depression, substance use, and suicide.
However, until now, the effects of childhood trauma have not been evaluated in a PD population.
As part of the MVP study, 712 adults with PD responded to an online survey asking about childhood trauma.
As anticipated, patients with the least reported childhood trauma reported the highest current QOL and lowest patient-reported motor and nonmotor symptom burden compared with peers with higher reported childhood trauma, the researchers reported.
PD symptom burden increased and QOL decreased as the number of ACEs increased.
Patients with ACE scores of 4 or higher reported greater PD symptom severity for 45% of the variables assessed, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (P < .05), compared with peers with trauma scores of 0.
Limitations of the study included the cross-sectional nature, which prevents making any causal determinations. Also, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk for recall bias. In addition, 65% of respondents were women, and racial and ethnic minority groups were not well represented.
Looking ahead, Dr. Subramanian and coauthors believe future research should “attempt to include more diverse populations, attempt improve the response rate of these sensitive questions and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.”
“As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization,” they suggested. “They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.”
Life experiences matter
In a comment, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said that “the idea that childhood trauma could be associated with a mild increase in severity of Parkinson’s symptoms such as apathy, pain, sleepiness and depression is fascinating.”
“We should however temper our enthusiasm for the results of this study because they were obtained through a direct patient survey, and not collected from large well characterized medical database,” Dr. Okun said.
He added” “If the data on childhood trauma and Parkinson’s can be replicated, we must ask why this could be?
“For Parkinson clinicians this as a reminder of how important obtaining a complete life history can be when strategizing on a plan to reduce motor and nonmotor Parkinson symptoms. Life experiences matter and can impact symptoms,” Dr. Okun said.
The MVP study was initiated with support of the National Center for Complementary and Integrative Health. The ongoing data collection has been supported by a donation from Sondra and Bill Fondren. Dr. Subramanian and Dr. Okun disclosed no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
new research shows.
Results of the first study to evaluate the relationship between childhood trauma and PD investigators found that the relationship appears to be dose dependent. Patients with PD who reported more than one ACE all experienced a statistically significant decrease in QOL, and for each additional ACE, there was significant worsening of motor symptoms.
This study supports a recent-call to-action paper in JAMA Neurology encouraging adoption of “trauma-informed neurology,” study investigator Indu Subramanian, MD, clinical professor, department of neurology, University of California, Los Angeles, said in an interview.
“We need to start asking about ACEs in everyone. It should be part of our medical intake,” said Dr. Subramanian, who is also the director of the Southwest Parkinson’s Disease Research, Education, and Clinical Center, West Los Angeles Veterans Affairs Medical Center.
The study was published online in Neurology: Clinical Practice.
Hard on the mind and body
A robust body of literature has clearly established a connection between ACEs, which include physical and emotional abuse, neglect, and household dysfunction, and negative physical health outcomes across the lifespan. These include stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature death as well as psychosocial health outcomes such as anxiety, depression, substance use, and suicide.
However, until now, the effects of childhood trauma have not been evaluated in a PD population.
As part of the MVP study, 712 adults with PD responded to an online survey asking about childhood trauma.
As anticipated, patients with the least reported childhood trauma reported the highest current QOL and lowest patient-reported motor and nonmotor symptom burden compared with peers with higher reported childhood trauma, the researchers reported.
PD symptom burden increased and QOL decreased as the number of ACEs increased.
Patients with ACE scores of 4 or higher reported greater PD symptom severity for 45% of the variables assessed, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (P < .05), compared with peers with trauma scores of 0.
Limitations of the study included the cross-sectional nature, which prevents making any causal determinations. Also, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk for recall bias. In addition, 65% of respondents were women, and racial and ethnic minority groups were not well represented.
Looking ahead, Dr. Subramanian and coauthors believe future research should “attempt to include more diverse populations, attempt improve the response rate of these sensitive questions and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.”
“As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization,” they suggested. “They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.”
Life experiences matter
In a comment, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said that “the idea that childhood trauma could be associated with a mild increase in severity of Parkinson’s symptoms such as apathy, pain, sleepiness and depression is fascinating.”
“We should however temper our enthusiasm for the results of this study because they were obtained through a direct patient survey, and not collected from large well characterized medical database,” Dr. Okun said.
He added” “If the data on childhood trauma and Parkinson’s can be replicated, we must ask why this could be?
“For Parkinson clinicians this as a reminder of how important obtaining a complete life history can be when strategizing on a plan to reduce motor and nonmotor Parkinson symptoms. Life experiences matter and can impact symptoms,” Dr. Okun said.
The MVP study was initiated with support of the National Center for Complementary and Integrative Health. The ongoing data collection has been supported by a donation from Sondra and Bill Fondren. Dr. Subramanian and Dr. Okun disclosed no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
new research shows.
Results of the first study to evaluate the relationship between childhood trauma and PD investigators found that the relationship appears to be dose dependent. Patients with PD who reported more than one ACE all experienced a statistically significant decrease in QOL, and for each additional ACE, there was significant worsening of motor symptoms.
This study supports a recent-call to-action paper in JAMA Neurology encouraging adoption of “trauma-informed neurology,” study investigator Indu Subramanian, MD, clinical professor, department of neurology, University of California, Los Angeles, said in an interview.
“We need to start asking about ACEs in everyone. It should be part of our medical intake,” said Dr. Subramanian, who is also the director of the Southwest Parkinson’s Disease Research, Education, and Clinical Center, West Los Angeles Veterans Affairs Medical Center.
The study was published online in Neurology: Clinical Practice.
Hard on the mind and body
A robust body of literature has clearly established a connection between ACEs, which include physical and emotional abuse, neglect, and household dysfunction, and negative physical health outcomes across the lifespan. These include stroke, dementia, diabetes, cancer, cardiovascular disease, autoimmune disorders, hypertension, and premature death as well as psychosocial health outcomes such as anxiety, depression, substance use, and suicide.
However, until now, the effects of childhood trauma have not been evaluated in a PD population.
As part of the MVP study, 712 adults with PD responded to an online survey asking about childhood trauma.
As anticipated, patients with the least reported childhood trauma reported the highest current QOL and lowest patient-reported motor and nonmotor symptom burden compared with peers with higher reported childhood trauma, the researchers reported.
PD symptom burden increased and QOL decreased as the number of ACEs increased.
Patients with ACE scores of 4 or higher reported greater PD symptom severity for 45% of the variables assessed, including apathy, muscle pain, daytime sleepiness, restless leg syndrome, depression, fatigue, comprehension, and anxiety (P < .05), compared with peers with trauma scores of 0.
Limitations of the study included the cross-sectional nature, which prevents making any causal determinations. Also, the ACE questionnaire, because it is self-reported and a retrospective collection of data, introduces the risk for recall bias. In addition, 65% of respondents were women, and racial and ethnic minority groups were not well represented.
Looking ahead, Dr. Subramanian and coauthors believe future research should “attempt to include more diverse populations, attempt improve the response rate of these sensitive questions and, most importantly, determine whether the adverse outcomes associated with childhood trauma can be mitigated with lifestyle modification, psychosocial support, and intervention in adulthood.”
“As a trauma-informed approach, something sorely lacking yet needed in the field of movement disorders, clinicians can proactively screen for ACEs while being mindful to avoid retraumatization,” they suggested. “They can begin to identify how ACEs may physiologically contribute to PD symptom and focus on targeting appropriate interventions that may improve outcomes.”
Life experiences matter
In a comment, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said that “the idea that childhood trauma could be associated with a mild increase in severity of Parkinson’s symptoms such as apathy, pain, sleepiness and depression is fascinating.”
“We should however temper our enthusiasm for the results of this study because they were obtained through a direct patient survey, and not collected from large well characterized medical database,” Dr. Okun said.
He added” “If the data on childhood trauma and Parkinson’s can be replicated, we must ask why this could be?
“For Parkinson clinicians this as a reminder of how important obtaining a complete life history can be when strategizing on a plan to reduce motor and nonmotor Parkinson symptoms. Life experiences matter and can impact symptoms,” Dr. Okun said.
The MVP study was initiated with support of the National Center for Complementary and Integrative Health. The ongoing data collection has been supported by a donation from Sondra and Bill Fondren. Dr. Subramanian and Dr. Okun disclosed no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY: CLINICAL PRACTICE
Does CRC risk in IBD extend to close family members?
new research suggests.
In a large Swedish study, a history of IBD among first-degree relatives was not associated with an increased risk of CRC, even when considering various characteristics of IBD and CRC history.
The findings suggest that extra screening for CRC may not be needed for children, siblings, or parents of those with IBD, say the study authors, led by Kai Wang, MD, PhD, with Harvard School of Public Health, Boston. The findings strengthen the theory that it’s inflammation or atypism of the colon of people with IBD that confers the increased CRC risk.
“There is nothing in this study that changes our existing practice,” said Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in the research. “It is already the thought that inflammation in IBD increases risk of cancer,” which would not increase CRC risk among family members.
The study appeared in the International Journal of Cancer.
Patients with IBD are known to be at increased risk for CRC. However, the association between family history of IBD and CRC risk remains less clear. Current CRC screening recommendations are the same for patients who have family members with IBD and for those who do not.
The Swedish nationwide case-control study included 69,659 individuals with CRC, of whom 1,599 (2.3%) had IBD, and 343,032 matched control persons who did not have CRC, of whom 1,477 (0.4%) had IBD.
Overall, 2.2% of CRC case patients and control patients had at least one first-degree relative who had a history of IBD.
After adjusting for family history of CRC, the authors did not find an increase in risk for CRC among first-degree relatives of people with IBD (odds ratio, 0.96; 95% confidence interval, 0.91-1.02).
The null association was consistently observed regardless of IBD subtype (Crohn’s disease or ulcerative colitis), the number of first-degree relatives with IBD, age at first IBD diagnosis, maximum location or extent of IBD, or type of relative (parent, sibling, or offspring). The null association remained for early-onset CRC diagnosed before age 50.
Overall, these findings suggest that IBD and CRC may not have substantial familial clustering or shared genetic susceptibility and provide “robust evidence that a family history of IBD did not increase the risk of CRC, supporting use of the same routine CRC screening strategy in offspring, siblings, and parents of IBD patients as in the general population,” Dr. Wang and colleagues conclude.
This “well-done” study is one of the largest to date to evaluate first-degree relatives of IBD patients and their risk of CRC, said Shannon Chang, MD, with NYU Langone Health Inflammatory Bowel Disease Center, who wasn’t involved in the research.
The findings are reassuring, as the authors assessed several factors and found that family members of patients with IBD are not at higher risk for CRC, compared with the general population, Dr. Chang added.
Support for the study was provided by the National Institutes of Health, the American Cancer Society, ALF funding, the Swedish Research Council, and the Swedish Cancer Foundation. Dr. Wang, Dr. Chang, and Dr. Ananthakrishnan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
In a large Swedish study, a history of IBD among first-degree relatives was not associated with an increased risk of CRC, even when considering various characteristics of IBD and CRC history.
The findings suggest that extra screening for CRC may not be needed for children, siblings, or parents of those with IBD, say the study authors, led by Kai Wang, MD, PhD, with Harvard School of Public Health, Boston. The findings strengthen the theory that it’s inflammation or atypism of the colon of people with IBD that confers the increased CRC risk.
“There is nothing in this study that changes our existing practice,” said Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in the research. “It is already the thought that inflammation in IBD increases risk of cancer,” which would not increase CRC risk among family members.
The study appeared in the International Journal of Cancer.
Patients with IBD are known to be at increased risk for CRC. However, the association between family history of IBD and CRC risk remains less clear. Current CRC screening recommendations are the same for patients who have family members with IBD and for those who do not.
The Swedish nationwide case-control study included 69,659 individuals with CRC, of whom 1,599 (2.3%) had IBD, and 343,032 matched control persons who did not have CRC, of whom 1,477 (0.4%) had IBD.
Overall, 2.2% of CRC case patients and control patients had at least one first-degree relative who had a history of IBD.
After adjusting for family history of CRC, the authors did not find an increase in risk for CRC among first-degree relatives of people with IBD (odds ratio, 0.96; 95% confidence interval, 0.91-1.02).
The null association was consistently observed regardless of IBD subtype (Crohn’s disease or ulcerative colitis), the number of first-degree relatives with IBD, age at first IBD diagnosis, maximum location or extent of IBD, or type of relative (parent, sibling, or offspring). The null association remained for early-onset CRC diagnosed before age 50.
Overall, these findings suggest that IBD and CRC may not have substantial familial clustering or shared genetic susceptibility and provide “robust evidence that a family history of IBD did not increase the risk of CRC, supporting use of the same routine CRC screening strategy in offspring, siblings, and parents of IBD patients as in the general population,” Dr. Wang and colleagues conclude.
This “well-done” study is one of the largest to date to evaluate first-degree relatives of IBD patients and their risk of CRC, said Shannon Chang, MD, with NYU Langone Health Inflammatory Bowel Disease Center, who wasn’t involved in the research.
The findings are reassuring, as the authors assessed several factors and found that family members of patients with IBD are not at higher risk for CRC, compared with the general population, Dr. Chang added.
Support for the study was provided by the National Institutes of Health, the American Cancer Society, ALF funding, the Swedish Research Council, and the Swedish Cancer Foundation. Dr. Wang, Dr. Chang, and Dr. Ananthakrishnan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
In a large Swedish study, a history of IBD among first-degree relatives was not associated with an increased risk of CRC, even when considering various characteristics of IBD and CRC history.
The findings suggest that extra screening for CRC may not be needed for children, siblings, or parents of those with IBD, say the study authors, led by Kai Wang, MD, PhD, with Harvard School of Public Health, Boston. The findings strengthen the theory that it’s inflammation or atypism of the colon of people with IBD that confers the increased CRC risk.
“There is nothing in this study that changes our existing practice,” said Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in the research. “It is already the thought that inflammation in IBD increases risk of cancer,” which would not increase CRC risk among family members.
The study appeared in the International Journal of Cancer.
Patients with IBD are known to be at increased risk for CRC. However, the association between family history of IBD and CRC risk remains less clear. Current CRC screening recommendations are the same for patients who have family members with IBD and for those who do not.
The Swedish nationwide case-control study included 69,659 individuals with CRC, of whom 1,599 (2.3%) had IBD, and 343,032 matched control persons who did not have CRC, of whom 1,477 (0.4%) had IBD.
Overall, 2.2% of CRC case patients and control patients had at least one first-degree relative who had a history of IBD.
After adjusting for family history of CRC, the authors did not find an increase in risk for CRC among first-degree relatives of people with IBD (odds ratio, 0.96; 95% confidence interval, 0.91-1.02).
The null association was consistently observed regardless of IBD subtype (Crohn’s disease or ulcerative colitis), the number of first-degree relatives with IBD, age at first IBD diagnosis, maximum location or extent of IBD, or type of relative (parent, sibling, or offspring). The null association remained for early-onset CRC diagnosed before age 50.
Overall, these findings suggest that IBD and CRC may not have substantial familial clustering or shared genetic susceptibility and provide “robust evidence that a family history of IBD did not increase the risk of CRC, supporting use of the same routine CRC screening strategy in offspring, siblings, and parents of IBD patients as in the general population,” Dr. Wang and colleagues conclude.
This “well-done” study is one of the largest to date to evaluate first-degree relatives of IBD patients and their risk of CRC, said Shannon Chang, MD, with NYU Langone Health Inflammatory Bowel Disease Center, who wasn’t involved in the research.
The findings are reassuring, as the authors assessed several factors and found that family members of patients with IBD are not at higher risk for CRC, compared with the general population, Dr. Chang added.
Support for the study was provided by the National Institutes of Health, the American Cancer Society, ALF funding, the Swedish Research Council, and the Swedish Cancer Foundation. Dr. Wang, Dr. Chang, and Dr. Ananthakrishnan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE INTERNATIONAL JOURNAL OF CANCER
FDA declines approval for omecamtiv mecarbil in HFrEF
The Food and Drug Administration has declined to approve omecamtiv mecarbil (Cytokinetics) for treatment of adults with chronic heart failure with reduced ejection fraction (HFrEF), citing a lack of evidence on efficacy.
Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.
Last December, a panel of FDA advisers recommended against approval of omecamtiv mecarbil for chronic HFrEF, as reported by this news organization.
The FDA Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF. The drug had a PDUFA date of February 28.
The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.
As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.
This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.
In a complete response letter, the FDA said GALACTIC-HF is “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death” in adults with HFrEF, Cytokinetics shared in a news release.
Further, the FDA said results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF, with benefits that outweigh the risks, Cytokinetics said.
The company said it will request a meeting with the FDA to gain a better understanding of what may be required to support potential approval of omecamtiv mecarbil. However, the company also said it has “no plans” to conduct an additional clinical trial of omecamtiv mecarbil.
Instead, the company said its focus remains on the development of aficamten, the next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, a phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has declined to approve omecamtiv mecarbil (Cytokinetics) for treatment of adults with chronic heart failure with reduced ejection fraction (HFrEF), citing a lack of evidence on efficacy.
Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.
Last December, a panel of FDA advisers recommended against approval of omecamtiv mecarbil for chronic HFrEF, as reported by this news organization.
The FDA Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF. The drug had a PDUFA date of February 28.
The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.
As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.
This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.
In a complete response letter, the FDA said GALACTIC-HF is “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death” in adults with HFrEF, Cytokinetics shared in a news release.
Further, the FDA said results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF, with benefits that outweigh the risks, Cytokinetics said.
The company said it will request a meeting with the FDA to gain a better understanding of what may be required to support potential approval of omecamtiv mecarbil. However, the company also said it has “no plans” to conduct an additional clinical trial of omecamtiv mecarbil.
Instead, the company said its focus remains on the development of aficamten, the next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, a phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has declined to approve omecamtiv mecarbil (Cytokinetics) for treatment of adults with chronic heart failure with reduced ejection fraction (HFrEF), citing a lack of evidence on efficacy.
Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.
Last December, a panel of FDA advisers recommended against approval of omecamtiv mecarbil for chronic HFrEF, as reported by this news organization.
The FDA Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF. The drug had a PDUFA date of February 28.
The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.
As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.
This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.
In a complete response letter, the FDA said GALACTIC-HF is “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death” in adults with HFrEF, Cytokinetics shared in a news release.
Further, the FDA said results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF, with benefits that outweigh the risks, Cytokinetics said.
The company said it will request a meeting with the FDA to gain a better understanding of what may be required to support potential approval of omecamtiv mecarbil. However, the company also said it has “no plans” to conduct an additional clinical trial of omecamtiv mecarbil.
Instead, the company said its focus remains on the development of aficamten, the next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, a phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy.
A version of this article first appeared on Medscape.com.
FDA warns of potential problems with Abbott Trifecta valves
There is a potential risk of early structural valve deterioration with the Abbott Trifecta valve and Trifecta valve with glide technology (Trifecta GT), the U.S. Food and Drug Administration says in a letter to health care professionals posted on its website.
Evidence in the literature suggests a higher cumulative incidence of early structural valve deterioration (SVD) and a lower freedom from reintervention due to SVD with the Trifecta valves, compared with other commercially available bovine pericardial valves, the FDA says.
The Trifecta and Trifecta GT valves are heart valve replacement devices intended to treat diseased, damaged, or malfunctioning native or prosthetic aortic heart valves, the letter notes. The first-generation Trifecta valve was approved in 2011 but is no longer marketed in the United States. The Trifecta GT valve was approved in 2016.
Medical device reports (MDRs) received by the FDA describe early SVD with Trifecta valves, with a peak time to SVD of 3 to 4 years post-implant. “Reported outcomes include surgical valve explant/replacement, transcatheter valve-in-valve intervention, and in some cases death,” the FDA notes.
In a letter to customers, Abbott says a “complaint analysis has shown that most cases of early SVD which occur within 5 years post-implant are characterized as a non-calcific leaflet tear, while most cases of late SVD which occur beyond 5 years post-implant are characterized as a fibrous-calcific SVD.”
The FDA recommends that health care providers take the following actions:
- Be aware of the potential risk of early SVD with Trifecta valves, and current patient management considerations, as communicated by Abbott.
- Discuss the risks and benefits of all available aortic valve treatment options with patients and caregivers as part of shared clinical decision-making prior to surgery.
- Read and carefully follow the Instructions for Use when implanting a Trifecta GT valve.
- Monitor patients who have undergone implantation with Trifecta valves for signs and symptoms of potential SVD.
- Instruct patients to seek medical attention with new onset of symptoms such as shortness of breath or fatigue.
- Ensure lifelong follow-up visits, conducted at least yearly, including transthoracic echocardiogram assessment of the valve beginning 1-year post-implant.
The FDA is working with Abbott to further evaluate the issue and develop additional patient management strategies, if needed. The FDA says it will continue to monitor the literature and reports of adverse events related to the issue.
Clinicians are encouraged to report any adverse events or quality problems with the Trifecta valves to their local Abbott representative or the customer service department at 1-800-544-1664.
Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
There is a potential risk of early structural valve deterioration with the Abbott Trifecta valve and Trifecta valve with glide technology (Trifecta GT), the U.S. Food and Drug Administration says in a letter to health care professionals posted on its website.
Evidence in the literature suggests a higher cumulative incidence of early structural valve deterioration (SVD) and a lower freedom from reintervention due to SVD with the Trifecta valves, compared with other commercially available bovine pericardial valves, the FDA says.
The Trifecta and Trifecta GT valves are heart valve replacement devices intended to treat diseased, damaged, or malfunctioning native or prosthetic aortic heart valves, the letter notes. The first-generation Trifecta valve was approved in 2011 but is no longer marketed in the United States. The Trifecta GT valve was approved in 2016.
Medical device reports (MDRs) received by the FDA describe early SVD with Trifecta valves, with a peak time to SVD of 3 to 4 years post-implant. “Reported outcomes include surgical valve explant/replacement, transcatheter valve-in-valve intervention, and in some cases death,” the FDA notes.
In a letter to customers, Abbott says a “complaint analysis has shown that most cases of early SVD which occur within 5 years post-implant are characterized as a non-calcific leaflet tear, while most cases of late SVD which occur beyond 5 years post-implant are characterized as a fibrous-calcific SVD.”
The FDA recommends that health care providers take the following actions:
- Be aware of the potential risk of early SVD with Trifecta valves, and current patient management considerations, as communicated by Abbott.
- Discuss the risks and benefits of all available aortic valve treatment options with patients and caregivers as part of shared clinical decision-making prior to surgery.
- Read and carefully follow the Instructions for Use when implanting a Trifecta GT valve.
- Monitor patients who have undergone implantation with Trifecta valves for signs and symptoms of potential SVD.
- Instruct patients to seek medical attention with new onset of symptoms such as shortness of breath or fatigue.
- Ensure lifelong follow-up visits, conducted at least yearly, including transthoracic echocardiogram assessment of the valve beginning 1-year post-implant.
The FDA is working with Abbott to further evaluate the issue and develop additional patient management strategies, if needed. The FDA says it will continue to monitor the literature and reports of adverse events related to the issue.
Clinicians are encouraged to report any adverse events or quality problems with the Trifecta valves to their local Abbott representative or the customer service department at 1-800-544-1664.
Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
There is a potential risk of early structural valve deterioration with the Abbott Trifecta valve and Trifecta valve with glide technology (Trifecta GT), the U.S. Food and Drug Administration says in a letter to health care professionals posted on its website.
Evidence in the literature suggests a higher cumulative incidence of early structural valve deterioration (SVD) and a lower freedom from reintervention due to SVD with the Trifecta valves, compared with other commercially available bovine pericardial valves, the FDA says.
The Trifecta and Trifecta GT valves are heart valve replacement devices intended to treat diseased, damaged, or malfunctioning native or prosthetic aortic heart valves, the letter notes. The first-generation Trifecta valve was approved in 2011 but is no longer marketed in the United States. The Trifecta GT valve was approved in 2016.
Medical device reports (MDRs) received by the FDA describe early SVD with Trifecta valves, with a peak time to SVD of 3 to 4 years post-implant. “Reported outcomes include surgical valve explant/replacement, transcatheter valve-in-valve intervention, and in some cases death,” the FDA notes.
In a letter to customers, Abbott says a “complaint analysis has shown that most cases of early SVD which occur within 5 years post-implant are characterized as a non-calcific leaflet tear, while most cases of late SVD which occur beyond 5 years post-implant are characterized as a fibrous-calcific SVD.”
The FDA recommends that health care providers take the following actions:
- Be aware of the potential risk of early SVD with Trifecta valves, and current patient management considerations, as communicated by Abbott.
- Discuss the risks and benefits of all available aortic valve treatment options with patients and caregivers as part of shared clinical decision-making prior to surgery.
- Read and carefully follow the Instructions for Use when implanting a Trifecta GT valve.
- Monitor patients who have undergone implantation with Trifecta valves for signs and symptoms of potential SVD.
- Instruct patients to seek medical attention with new onset of symptoms such as shortness of breath or fatigue.
- Ensure lifelong follow-up visits, conducted at least yearly, including transthoracic echocardiogram assessment of the valve beginning 1-year post-implant.
The FDA is working with Abbott to further evaluate the issue and develop additional patient management strategies, if needed. The FDA says it will continue to monitor the literature and reports of adverse events related to the issue.
Clinicians are encouraged to report any adverse events or quality problems with the Trifecta valves to their local Abbott representative or the customer service department at 1-800-544-1664.
Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Regular laxative use tied to increased dementia risk
Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.
Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.
“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.
“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.
The study was published online in Neurology.
Robust link
The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.
A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.
Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.
After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).
The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.
Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).
“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.
They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
Interpret with caution
Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”
However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”
Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”
The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.
“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.
The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.
Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.
“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.
“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.
The study was published online in Neurology.
Robust link
The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.
A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.
Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.
After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).
The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.
Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).
“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.
They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
Interpret with caution
Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”
However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”
Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”
The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.
“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.
The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.
Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.
“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.
“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.
The study was published online in Neurology.
Robust link
The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.
A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.
Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.
After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).
The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.
Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).
“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.
They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
Interpret with caution
Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”
However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”
Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”
The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.
“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.
The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM NEUROLOGY
Real-world survival benefit with CDK4/6 inhibitors in MBC
(MBC).
Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone versus 73% with endocrine therapy plus a CDK4/6 inhibitor – findings largely consistent with clinical trial data.
Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR-positive/HER2-negative MBC,” the researchers concluded.
The study was published online in the journal Cancer.
The Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3, randomized, controlled trial data.
Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.
To address these gaps, Ravi Goyal, PhD, with the University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results Medicare database.
Dr. Goyal and coauthors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.
The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy–alone group and 30 months in the combination therapy group.
In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group versus49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy–only group.
In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio, 0.59).
Dr. Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.
In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group versus 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.
In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).
The coauthors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.
Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston, noted that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.
The work of Dr. Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” Dr. Trapani and Dr. Mayer wrote.
The study had no specific funding. The authors and Dr. Trapani disclosed no relevant financial relaitonships. Dr. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.
A version of this article first appeared on Medscape.com.
(MBC).
Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone versus 73% with endocrine therapy plus a CDK4/6 inhibitor – findings largely consistent with clinical trial data.
Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR-positive/HER2-negative MBC,” the researchers concluded.
The study was published online in the journal Cancer.
The Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3, randomized, controlled trial data.
Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.
To address these gaps, Ravi Goyal, PhD, with the University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results Medicare database.
Dr. Goyal and coauthors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.
The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy–alone group and 30 months in the combination therapy group.
In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group versus49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy–only group.
In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio, 0.59).
Dr. Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.
In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group versus 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.
In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).
The coauthors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.
Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston, noted that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.
The work of Dr. Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” Dr. Trapani and Dr. Mayer wrote.
The study had no specific funding. The authors and Dr. Trapani disclosed no relevant financial relaitonships. Dr. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.
A version of this article first appeared on Medscape.com.
(MBC).
Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone versus 73% with endocrine therapy plus a CDK4/6 inhibitor – findings largely consistent with clinical trial data.
Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR-positive/HER2-negative MBC,” the researchers concluded.
The study was published online in the journal Cancer.
The Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3, randomized, controlled trial data.
Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.
To address these gaps, Ravi Goyal, PhD, with the University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results Medicare database.
Dr. Goyal and coauthors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.
The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy–alone group and 30 months in the combination therapy group.
In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group versus49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy–only group.
In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio, 0.59).
Dr. Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.
In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group versus 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.
In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).
The coauthors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.
Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston, noted that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.
The work of Dr. Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” Dr. Trapani and Dr. Mayer wrote.
The study had no specific funding. The authors and Dr. Trapani disclosed no relevant financial relaitonships. Dr. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.
A version of this article first appeared on Medscape.com.
FROM CANCER
Spinal cord stimulation restores poststroke arm, hand function in two patients
The results provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” wrote first author Marc P. Powell, PhD, of Reach Neuro Inc., Pittsburgh, and colleagues.
The findings were published online in Nature Medicine.
Top cause of paralysis
“Stroke is the largest cause of paralysis in the world,” with nearly three-quarters of patients with stroke experiencing lasting deficits in motor control of their arm and hand, co–senior study author Marco Capogrosso, PhD, assistant professor of neurological surgery at the University of Pittsburgh, said during a press briefing.
Stroke can disrupt communication between the brain and the spinal cord, leading to motor deficits in the arm and hand. However, below the lesion, the spinal circuits that control movement remain intact and could be targeted to restore function, Dr. Capogrosso noted.
Spinal cord stimulation has shown promise in promoting long-lasting recovery of leg motor function in patients with spinal cord injury; but until now, it’s been largely unexplored for upper-limb recovery.
In this “first-in-human” study, the investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two patients.
One of the patients was a woman (age, 31 years) who had experienced a right thalamic hemorrhagic stroke secondary to a cavernous malformation 9 years before enrolling in the pilot study.
The other patient was a woman (age, 47 years) who experienced a right ischemic middle cerebral artery (MCA) stroke secondary to a right carotid dissection, resulting in a large MCA territory infarct 3 years before entering the study.
In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.
The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that the younger woman had not been able to do for 9 years.
“Perhaps even more interesting, we found that after a few weeks of use, some of these improvements endure when the stimulation is switched off, indicating exciting avenues for the future of stroke therapies,” Dr. Capogrosso said in a news release.
No serious adverse events were reported.
‘Easily translated’
Dr. Capogrosso said that, thanks to years of preclinical research, the investigators have developed a practical, easy-to-use stimulation protocol adapting existing clinical technologies that “could be easily translated to the hospital and quickly moved from the lab to the clinic.”
The researchers noted, however, that further studies in larger cohorts will be required to validate the safety and efficacy of this approach.
They are currently working with more patients with stroke to fine-tune placement of the leads and stimulation protocol, as well as determine which patients are best suited for the approach.
“Creating effective neurorehabilitation solutions for people affected by movement impairment after stroke is becoming ever more urgent,” co–senior author Elvira Pirondini, PhD, assistant professor of physical medicine and rehabilitation at the University of Pittsburgh, said in the release.
“Even mild deficits resulting from a stroke can isolate people from social and professional lives and become very debilitating, with motor impairments in the arm and hand being especially taxing and impeding simple daily activities, such as writing, eating, and getting dressed,” she added.
This research was funded by the National Institutes of Health BRAIN Initiative, with additional research support provided by the Department of Neurological Surgery and the Department of Physical Medicine and Rehabilitation at Pitt, and the Department of Mechanical Engineering and the Neuroscience Institute at Carnegie Mellon University. Three investigators have financial interests in Reach Neuro, which has an interest in the technology being evaluated in this study.
A version of this article first appeared on Medscape.com.
The results provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” wrote first author Marc P. Powell, PhD, of Reach Neuro Inc., Pittsburgh, and colleagues.
The findings were published online in Nature Medicine.
Top cause of paralysis
“Stroke is the largest cause of paralysis in the world,” with nearly three-quarters of patients with stroke experiencing lasting deficits in motor control of their arm and hand, co–senior study author Marco Capogrosso, PhD, assistant professor of neurological surgery at the University of Pittsburgh, said during a press briefing.
Stroke can disrupt communication between the brain and the spinal cord, leading to motor deficits in the arm and hand. However, below the lesion, the spinal circuits that control movement remain intact and could be targeted to restore function, Dr. Capogrosso noted.
Spinal cord stimulation has shown promise in promoting long-lasting recovery of leg motor function in patients with spinal cord injury; but until now, it’s been largely unexplored for upper-limb recovery.
In this “first-in-human” study, the investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two patients.
One of the patients was a woman (age, 31 years) who had experienced a right thalamic hemorrhagic stroke secondary to a cavernous malformation 9 years before enrolling in the pilot study.
The other patient was a woman (age, 47 years) who experienced a right ischemic middle cerebral artery (MCA) stroke secondary to a right carotid dissection, resulting in a large MCA territory infarct 3 years before entering the study.
In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.
The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that the younger woman had not been able to do for 9 years.
“Perhaps even more interesting, we found that after a few weeks of use, some of these improvements endure when the stimulation is switched off, indicating exciting avenues for the future of stroke therapies,” Dr. Capogrosso said in a news release.
No serious adverse events were reported.
‘Easily translated’
Dr. Capogrosso said that, thanks to years of preclinical research, the investigators have developed a practical, easy-to-use stimulation protocol adapting existing clinical technologies that “could be easily translated to the hospital and quickly moved from the lab to the clinic.”
The researchers noted, however, that further studies in larger cohorts will be required to validate the safety and efficacy of this approach.
They are currently working with more patients with stroke to fine-tune placement of the leads and stimulation protocol, as well as determine which patients are best suited for the approach.
“Creating effective neurorehabilitation solutions for people affected by movement impairment after stroke is becoming ever more urgent,” co–senior author Elvira Pirondini, PhD, assistant professor of physical medicine and rehabilitation at the University of Pittsburgh, said in the release.
“Even mild deficits resulting from a stroke can isolate people from social and professional lives and become very debilitating, with motor impairments in the arm and hand being especially taxing and impeding simple daily activities, such as writing, eating, and getting dressed,” she added.
This research was funded by the National Institutes of Health BRAIN Initiative, with additional research support provided by the Department of Neurological Surgery and the Department of Physical Medicine and Rehabilitation at Pitt, and the Department of Mechanical Engineering and the Neuroscience Institute at Carnegie Mellon University. Three investigators have financial interests in Reach Neuro, which has an interest in the technology being evaluated in this study.
A version of this article first appeared on Medscape.com.
The results provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” wrote first author Marc P. Powell, PhD, of Reach Neuro Inc., Pittsburgh, and colleagues.
The findings were published online in Nature Medicine.
Top cause of paralysis
“Stroke is the largest cause of paralysis in the world,” with nearly three-quarters of patients with stroke experiencing lasting deficits in motor control of their arm and hand, co–senior study author Marco Capogrosso, PhD, assistant professor of neurological surgery at the University of Pittsburgh, said during a press briefing.
Stroke can disrupt communication between the brain and the spinal cord, leading to motor deficits in the arm and hand. However, below the lesion, the spinal circuits that control movement remain intact and could be targeted to restore function, Dr. Capogrosso noted.
Spinal cord stimulation has shown promise in promoting long-lasting recovery of leg motor function in patients with spinal cord injury; but until now, it’s been largely unexplored for upper-limb recovery.
In this “first-in-human” study, the investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two patients.
One of the patients was a woman (age, 31 years) who had experienced a right thalamic hemorrhagic stroke secondary to a cavernous malformation 9 years before enrolling in the pilot study.
The other patient was a woman (age, 47 years) who experienced a right ischemic middle cerebral artery (MCA) stroke secondary to a right carotid dissection, resulting in a large MCA territory infarct 3 years before entering the study.
In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.
The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that the younger woman had not been able to do for 9 years.
“Perhaps even more interesting, we found that after a few weeks of use, some of these improvements endure when the stimulation is switched off, indicating exciting avenues for the future of stroke therapies,” Dr. Capogrosso said in a news release.
No serious adverse events were reported.
‘Easily translated’
Dr. Capogrosso said that, thanks to years of preclinical research, the investigators have developed a practical, easy-to-use stimulation protocol adapting existing clinical technologies that “could be easily translated to the hospital and quickly moved from the lab to the clinic.”
The researchers noted, however, that further studies in larger cohorts will be required to validate the safety and efficacy of this approach.
They are currently working with more patients with stroke to fine-tune placement of the leads and stimulation protocol, as well as determine which patients are best suited for the approach.
“Creating effective neurorehabilitation solutions for people affected by movement impairment after stroke is becoming ever more urgent,” co–senior author Elvira Pirondini, PhD, assistant professor of physical medicine and rehabilitation at the University of Pittsburgh, said in the release.
“Even mild deficits resulting from a stroke can isolate people from social and professional lives and become very debilitating, with motor impairments in the arm and hand being especially taxing and impeding simple daily activities, such as writing, eating, and getting dressed,” she added.
This research was funded by the National Institutes of Health BRAIN Initiative, with additional research support provided by the Department of Neurological Surgery and the Department of Physical Medicine and Rehabilitation at Pitt, and the Department of Mechanical Engineering and the Neuroscience Institute at Carnegie Mellon University. Three investigators have financial interests in Reach Neuro, which has an interest in the technology being evaluated in this study.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
Cardiologists weigh in on ethically challenging issues
Would you tell a patient about a potentially harmful medical mistake? Would you upcode or overstate a patient’s condition so an insurer will cover it? What about reporting a colleague who seems impaired or engages in sexual harassment or bullying?
In a new survey, this news organization asked more than 4,100 U.S. physicians how they would react to these and other ethically challenging scenarios.
For example, a full 80% of cardiologists responding to the survey said they would reveal a potentially harmful medical mistake to their patient.
This aligns with decades of advice from major medical societies such as the American Medical Association and the American College of Physicians, which endorse disclosing to patients and families any error that could jeopardize the patient’s health.
“Disclosure of close calls should also be made. From a health law context, being upfront with the patient is standard practice,” said Eric Mathison, PhD, a clinical ethicist at University of Toronto.
When it comes to upcoding or overstating a patient’s condition so an insurer will cover it, more than three quarters of cardiologists (78%) viewed this as unacceptable, while 9% felt it was okay and 13% said “it depends.”
Many doctors are willing to stretch coding policies to the limit to support patients and their finances, said Arthur L. Caplan, PhD, NYU professor of bioethics and Medscape blogger. “That’s acceptable advocacy. But most doctors will not say they are willing to commit fraud.”
Okay to breach patient confidentiality?
More than half of cardiologists felt it was okay to breach patient confidentiality when someone’s health could be threatened, 14% felt the opposite, and 29% said it depends.
“I teach that if you know someone faces a direct risk from catching a deadly disease, and you know who that person is, then you have a duty to warn,” Dr. Caplan said. “The disease has to be serious for [breaching confidentiality] to be morally defensible, and your disclosure has to be actionable. Telling your mother won’t achieve a lot” in protecting someone’s health.
In a 2020 ethics survey by this news organization, 72% of cardiologists felt that they could accept a meal or speaking gig from a drug company without its creating any issue for them.
Three years later, only 66% of cardiologists said they could accept a meal or speaking engagement without its influencing their prescribing habits; 21% said they couldn’t and 13% said it depends.
Dr. Caplan thinks that many doctors are deceiving themselves. “We know from business school case studies that even little gifts like calendars and flashlights work. Humans get a sense of debt when they receive gifts. Physicians are no exception. If you get a meal or an invitation to do a talk for a small fee, you may still say, ‘This is nothing to me,’ ” but subconscious favoritism can result, he cautioned.
Support for physician-assisted dying?
Ten states and the District of Columbia now allow physicians to help a terminally ill patient with dying. Fifty percent of cardiologists surveyed support it, 36% are against it, and 14% said it depends. These percentages are roughly the same as in 2020.
Dr. Mathison said the public and physicians are “getting more comfortable with physician-assisted dying. Physicians are seeing it used in practice and hearing from other physicians who are participating.”
However, only 31% of cardiologists felt physician-assisted dying should be allowed for patients in intractable pain; 42% said it should not be legal in this case, and 26% said it depends.
As opposed to physician-assisted dying for terminally ill patients, no U.S. state recognizes the legal right to help end the life of a patient in unending pain. However, Belgium, the Netherlands, and Luxembourg do under certain conditions.
Going public about issues with a cardiologist’s hospital or health care organization became a major issue during the COVID-19 pandemic as some medical professionals struggled to get enough personal protective equipment and made it known.
More than half of cardiologists surveyed (53%) endorsed speaking out if employers don’t provide needed resources; 9% didn’t feel this was appropriate, and 28% said it depends.
Dr. Caplan noted that prominent cases of hospitals firing nurses and doctors who complained over social media may influence cardiologists’ willingness. He also thinks some doctors would ask, “Speak out to whom?” Many cardiologists will aggressively push for resources through the internal chain of command “but don’t think talking to the media is ethical or appropriate.”
The vast majority of cardiologists and physicians overall said they have never failed to report or investigate suspected domestic abuse of a patient.
Both male and female physicians strongly support reporting of abuse cases, said Thomas May, PhD, a bioethicist at Washington State University, Spokane.
This reflects the “tremendous strides society has made in recognizing the impact of abuse and the need for required-reporting policies, because victims are often, if not usually, reticent to come forward. Required reporting is necessary and in the patient’s interests,” Dr. May said.
Romancing a patient?
More than half (58%) of cardiologists felt that having a romantic relationship with a current patient is not okay; 3% were okay with it, and 30% felt it would be okay at least 6 months after the patient-doctor relationship ended.
Dr. May said a romantic relationship is “inappropriate while the professional relationship is active and even for some time afterward. There’s a professional dynamic that needs to be maintained, a sense of objectivity.
“Plus, the physician is in a power relationship to the patient where there’s a sense of gratefulness or vulnerability that makes the patient unable to say no to a personal relationship,” Dr. May said.
Dr. May is not sure 6 months after they stop being your patient is long enough. “I’d think something like 2 years as a minimum. If I were your oncologist and helped save your life, it may never be appropriate,” Dr. May said.
In other ethical questions, one-quarter of cardiologists would report a doctor who seems impaired by drugs, alcohol, or illness, and 62% would do so only after speaking to him/her first.
“Our obligation is to do no harm to patients, and the professional standards and integrity of the profession are at stake,” one survey respondent said.
Another said, “A colleague who recognizes the problem and after private discussion enters a treatment program is often better served than by the often excessively harsh management by the state medical board.”
But when it comes to random alcohol and drug tests for cardiologists, 51% are not in favor, 31% are in favor, and 18% said it depends.
Dr. Caplan thinks that physicians face enough responsibility to patients to warrant such testing randomly but infrequently. “Doctors may feel like they’re being treated unprofessionally, like drug addicts, or question the accuracy of testing,” he noted. But he tilts instead toward “the moral fight to protect patient safety and trying to drive down malpractice costs.”
When it comes to reporting a colleague for sexual harassment or bullying, 71% of cardiologists said yes, they would report such behavior; only 7% would not, while 22% said it depends.
“If we ignore bad behavior such as this by our colleagues, then we are hurting our profession,” one physician said.
A version of this article originally appeared on Medscape.com.
Would you tell a patient about a potentially harmful medical mistake? Would you upcode or overstate a patient’s condition so an insurer will cover it? What about reporting a colleague who seems impaired or engages in sexual harassment or bullying?
In a new survey, this news organization asked more than 4,100 U.S. physicians how they would react to these and other ethically challenging scenarios.
For example, a full 80% of cardiologists responding to the survey said they would reveal a potentially harmful medical mistake to their patient.
This aligns with decades of advice from major medical societies such as the American Medical Association and the American College of Physicians, which endorse disclosing to patients and families any error that could jeopardize the patient’s health.
“Disclosure of close calls should also be made. From a health law context, being upfront with the patient is standard practice,” said Eric Mathison, PhD, a clinical ethicist at University of Toronto.
When it comes to upcoding or overstating a patient’s condition so an insurer will cover it, more than three quarters of cardiologists (78%) viewed this as unacceptable, while 9% felt it was okay and 13% said “it depends.”
Many doctors are willing to stretch coding policies to the limit to support patients and their finances, said Arthur L. Caplan, PhD, NYU professor of bioethics and Medscape blogger. “That’s acceptable advocacy. But most doctors will not say they are willing to commit fraud.”
Okay to breach patient confidentiality?
More than half of cardiologists felt it was okay to breach patient confidentiality when someone’s health could be threatened, 14% felt the opposite, and 29% said it depends.
“I teach that if you know someone faces a direct risk from catching a deadly disease, and you know who that person is, then you have a duty to warn,” Dr. Caplan said. “The disease has to be serious for [breaching confidentiality] to be morally defensible, and your disclosure has to be actionable. Telling your mother won’t achieve a lot” in protecting someone’s health.
In a 2020 ethics survey by this news organization, 72% of cardiologists felt that they could accept a meal or speaking gig from a drug company without its creating any issue for them.
Three years later, only 66% of cardiologists said they could accept a meal or speaking engagement without its influencing their prescribing habits; 21% said they couldn’t and 13% said it depends.
Dr. Caplan thinks that many doctors are deceiving themselves. “We know from business school case studies that even little gifts like calendars and flashlights work. Humans get a sense of debt when they receive gifts. Physicians are no exception. If you get a meal or an invitation to do a talk for a small fee, you may still say, ‘This is nothing to me,’ ” but subconscious favoritism can result, he cautioned.
Support for physician-assisted dying?
Ten states and the District of Columbia now allow physicians to help a terminally ill patient with dying. Fifty percent of cardiologists surveyed support it, 36% are against it, and 14% said it depends. These percentages are roughly the same as in 2020.
Dr. Mathison said the public and physicians are “getting more comfortable with physician-assisted dying. Physicians are seeing it used in practice and hearing from other physicians who are participating.”
However, only 31% of cardiologists felt physician-assisted dying should be allowed for patients in intractable pain; 42% said it should not be legal in this case, and 26% said it depends.
As opposed to physician-assisted dying for terminally ill patients, no U.S. state recognizes the legal right to help end the life of a patient in unending pain. However, Belgium, the Netherlands, and Luxembourg do under certain conditions.
Going public about issues with a cardiologist’s hospital or health care organization became a major issue during the COVID-19 pandemic as some medical professionals struggled to get enough personal protective equipment and made it known.
More than half of cardiologists surveyed (53%) endorsed speaking out if employers don’t provide needed resources; 9% didn’t feel this was appropriate, and 28% said it depends.
Dr. Caplan noted that prominent cases of hospitals firing nurses and doctors who complained over social media may influence cardiologists’ willingness. He also thinks some doctors would ask, “Speak out to whom?” Many cardiologists will aggressively push for resources through the internal chain of command “but don’t think talking to the media is ethical or appropriate.”
The vast majority of cardiologists and physicians overall said they have never failed to report or investigate suspected domestic abuse of a patient.
Both male and female physicians strongly support reporting of abuse cases, said Thomas May, PhD, a bioethicist at Washington State University, Spokane.
This reflects the “tremendous strides society has made in recognizing the impact of abuse and the need for required-reporting policies, because victims are often, if not usually, reticent to come forward. Required reporting is necessary and in the patient’s interests,” Dr. May said.
Romancing a patient?
More than half (58%) of cardiologists felt that having a romantic relationship with a current patient is not okay; 3% were okay with it, and 30% felt it would be okay at least 6 months after the patient-doctor relationship ended.
Dr. May said a romantic relationship is “inappropriate while the professional relationship is active and even for some time afterward. There’s a professional dynamic that needs to be maintained, a sense of objectivity.
“Plus, the physician is in a power relationship to the patient where there’s a sense of gratefulness or vulnerability that makes the patient unable to say no to a personal relationship,” Dr. May said.
Dr. May is not sure 6 months after they stop being your patient is long enough. “I’d think something like 2 years as a minimum. If I were your oncologist and helped save your life, it may never be appropriate,” Dr. May said.
In other ethical questions, one-quarter of cardiologists would report a doctor who seems impaired by drugs, alcohol, or illness, and 62% would do so only after speaking to him/her first.
“Our obligation is to do no harm to patients, and the professional standards and integrity of the profession are at stake,” one survey respondent said.
Another said, “A colleague who recognizes the problem and after private discussion enters a treatment program is often better served than by the often excessively harsh management by the state medical board.”
But when it comes to random alcohol and drug tests for cardiologists, 51% are not in favor, 31% are in favor, and 18% said it depends.
Dr. Caplan thinks that physicians face enough responsibility to patients to warrant such testing randomly but infrequently. “Doctors may feel like they’re being treated unprofessionally, like drug addicts, or question the accuracy of testing,” he noted. But he tilts instead toward “the moral fight to protect patient safety and trying to drive down malpractice costs.”
When it comes to reporting a colleague for sexual harassment or bullying, 71% of cardiologists said yes, they would report such behavior; only 7% would not, while 22% said it depends.
“If we ignore bad behavior such as this by our colleagues, then we are hurting our profession,” one physician said.
A version of this article originally appeared on Medscape.com.
Would you tell a patient about a potentially harmful medical mistake? Would you upcode or overstate a patient’s condition so an insurer will cover it? What about reporting a colleague who seems impaired or engages in sexual harassment or bullying?
In a new survey, this news organization asked more than 4,100 U.S. physicians how they would react to these and other ethically challenging scenarios.
For example, a full 80% of cardiologists responding to the survey said they would reveal a potentially harmful medical mistake to their patient.
This aligns with decades of advice from major medical societies such as the American Medical Association and the American College of Physicians, which endorse disclosing to patients and families any error that could jeopardize the patient’s health.
“Disclosure of close calls should also be made. From a health law context, being upfront with the patient is standard practice,” said Eric Mathison, PhD, a clinical ethicist at University of Toronto.
When it comes to upcoding or overstating a patient’s condition so an insurer will cover it, more than three quarters of cardiologists (78%) viewed this as unacceptable, while 9% felt it was okay and 13% said “it depends.”
Many doctors are willing to stretch coding policies to the limit to support patients and their finances, said Arthur L. Caplan, PhD, NYU professor of bioethics and Medscape blogger. “That’s acceptable advocacy. But most doctors will not say they are willing to commit fraud.”
Okay to breach patient confidentiality?
More than half of cardiologists felt it was okay to breach patient confidentiality when someone’s health could be threatened, 14% felt the opposite, and 29% said it depends.
“I teach that if you know someone faces a direct risk from catching a deadly disease, and you know who that person is, then you have a duty to warn,” Dr. Caplan said. “The disease has to be serious for [breaching confidentiality] to be morally defensible, and your disclosure has to be actionable. Telling your mother won’t achieve a lot” in protecting someone’s health.
In a 2020 ethics survey by this news organization, 72% of cardiologists felt that they could accept a meal or speaking gig from a drug company without its creating any issue for them.
Three years later, only 66% of cardiologists said they could accept a meal or speaking engagement without its influencing their prescribing habits; 21% said they couldn’t and 13% said it depends.
Dr. Caplan thinks that many doctors are deceiving themselves. “We know from business school case studies that even little gifts like calendars and flashlights work. Humans get a sense of debt when they receive gifts. Physicians are no exception. If you get a meal or an invitation to do a talk for a small fee, you may still say, ‘This is nothing to me,’ ” but subconscious favoritism can result, he cautioned.
Support for physician-assisted dying?
Ten states and the District of Columbia now allow physicians to help a terminally ill patient with dying. Fifty percent of cardiologists surveyed support it, 36% are against it, and 14% said it depends. These percentages are roughly the same as in 2020.
Dr. Mathison said the public and physicians are “getting more comfortable with physician-assisted dying. Physicians are seeing it used in practice and hearing from other physicians who are participating.”
However, only 31% of cardiologists felt physician-assisted dying should be allowed for patients in intractable pain; 42% said it should not be legal in this case, and 26% said it depends.
As opposed to physician-assisted dying for terminally ill patients, no U.S. state recognizes the legal right to help end the life of a patient in unending pain. However, Belgium, the Netherlands, and Luxembourg do under certain conditions.
Going public about issues with a cardiologist’s hospital or health care organization became a major issue during the COVID-19 pandemic as some medical professionals struggled to get enough personal protective equipment and made it known.
More than half of cardiologists surveyed (53%) endorsed speaking out if employers don’t provide needed resources; 9% didn’t feel this was appropriate, and 28% said it depends.
Dr. Caplan noted that prominent cases of hospitals firing nurses and doctors who complained over social media may influence cardiologists’ willingness. He also thinks some doctors would ask, “Speak out to whom?” Many cardiologists will aggressively push for resources through the internal chain of command “but don’t think talking to the media is ethical or appropriate.”
The vast majority of cardiologists and physicians overall said they have never failed to report or investigate suspected domestic abuse of a patient.
Both male and female physicians strongly support reporting of abuse cases, said Thomas May, PhD, a bioethicist at Washington State University, Spokane.
This reflects the “tremendous strides society has made in recognizing the impact of abuse and the need for required-reporting policies, because victims are often, if not usually, reticent to come forward. Required reporting is necessary and in the patient’s interests,” Dr. May said.
Romancing a patient?
More than half (58%) of cardiologists felt that having a romantic relationship with a current patient is not okay; 3% were okay with it, and 30% felt it would be okay at least 6 months after the patient-doctor relationship ended.
Dr. May said a romantic relationship is “inappropriate while the professional relationship is active and even for some time afterward. There’s a professional dynamic that needs to be maintained, a sense of objectivity.
“Plus, the physician is in a power relationship to the patient where there’s a sense of gratefulness or vulnerability that makes the patient unable to say no to a personal relationship,” Dr. May said.
Dr. May is not sure 6 months after they stop being your patient is long enough. “I’d think something like 2 years as a minimum. If I were your oncologist and helped save your life, it may never be appropriate,” Dr. May said.
In other ethical questions, one-quarter of cardiologists would report a doctor who seems impaired by drugs, alcohol, or illness, and 62% would do so only after speaking to him/her first.
“Our obligation is to do no harm to patients, and the professional standards and integrity of the profession are at stake,” one survey respondent said.
Another said, “A colleague who recognizes the problem and after private discussion enters a treatment program is often better served than by the often excessively harsh management by the state medical board.”
But when it comes to random alcohol and drug tests for cardiologists, 51% are not in favor, 31% are in favor, and 18% said it depends.
Dr. Caplan thinks that physicians face enough responsibility to patients to warrant such testing randomly but infrequently. “Doctors may feel like they’re being treated unprofessionally, like drug addicts, or question the accuracy of testing,” he noted. But he tilts instead toward “the moral fight to protect patient safety and trying to drive down malpractice costs.”
When it comes to reporting a colleague for sexual harassment or bullying, 71% of cardiologists said yes, they would report such behavior; only 7% would not, while 22% said it depends.
“If we ignore bad behavior such as this by our colleagues, then we are hurting our profession,” one physician said.
A version of this article originally appeared on Medscape.com.
Cold snare polypectomy tops hot snare for small polyps
In the Taiwan Cold Polypectomy Study, CSP was not only safer than HSP, with a significantly lower risk for delayed bleeding, it was also more efficient, report Li-Chun Chang, MD, PhD, from the National Taiwan University Hospital, Taipei, and colleagues.
The study was published online in Annals of Internal Medicine.
This large study “strengthens the already significant evidence that CSP is as effective and safer than HSP for polyps 4-10 mm in size,” Rajesh N. Keswani, MD, Northwestern University, Chicago, told this news organization.
“This study evaluated all significant endpoints – safety (decreased bleeding risk with CSP), effectiveness (equivalent complete resection rates between CSP and HSP), and efficiency (CSP faster than HSP),” said Dr. Keswani, who wasn’t involved in the study.
Previous randomized controlled trials have shown that CSP is as effective as HSP but more efficient in removing small polyps. The reduction in delayed bleeding associated with CSP had been shown only in high-risk patients using antiplatelet agents or anticoagulants, however. Less was known about CSP’s effect on delayed bleeding in the general population.
To investigate, Dr. Chang and colleagues randomly assigned 4,270 adults aged 40 and older who were undergoing polypectomy to remove polyps measuring 4-10 mm to CSP or HSP.
Compared with HSP, CSP was associated with a significantly lower risk for all delayed bleeding (within 14 days after polypectomy) and severe delayed bleeding (defined as a decrease in hemoglobin of 20 g/L or more, requiring transfusion or hemostasis).
Eight of 2,137 patients (0.4%) in the CSP group had delayed bleeding versus 31 of 2,133 patients (1.5%) in the HSP group. Severe bleeding occurred in one patient who had CSP (0.05%) and eight who had HSP (0.4%).
The CSP group also had fewer emergency service visits than the HSP group – 4 visits (0.2%) versus 13 visits (0.6%).
CSP was more efficient, with mean polypectomy time reduced 26.9%, compared with HSP, with no difference between groups in successful tissue retrieval, en bloc resection, and complete histologic resection.
“CSP saves time setting up electrosurgical generators or conducting submucosal injection. Moreover, the lower rate of delayed bleeding means fewer emergency service visits or hospital stays, saving medical expenses,” Dr. Chang and colleagues write in their article.
“Given the benefit in safety and cost-effectiveness, CSP may replace HSP for removal of small polyps in the general population,” they add.
Dr. Keswani agreed. “Based on the accumulated evidence over the past decade, CSP is the clear standard of care for polyps 4-10 mm in size,” he said in an interview.
“For polyps less than 4 mm, it remains reasonable to use either large capacity/jumbo forceps or CSP. Cautery should be reserved only for polyps greater than 10 mm, although there is ongoing work regarding cold versus hot EMR [endoscopic mucosal resection],” Dr. Keswani said.
The trial was principal investigator–initiated and partially funded by Boston Scientific, which had no role in the study design, data collection or analysis, data interpretation, manuscript preparation, or decision to submit the manuscript for publication. Dr. Keswani is a consultant for Boston Scientific and Neptune Medical and receives research support from Virgo.
A version of this article first appeared on Medscape.com.
In the Taiwan Cold Polypectomy Study, CSP was not only safer than HSP, with a significantly lower risk for delayed bleeding, it was also more efficient, report Li-Chun Chang, MD, PhD, from the National Taiwan University Hospital, Taipei, and colleagues.
The study was published online in Annals of Internal Medicine.
This large study “strengthens the already significant evidence that CSP is as effective and safer than HSP for polyps 4-10 mm in size,” Rajesh N. Keswani, MD, Northwestern University, Chicago, told this news organization.
“This study evaluated all significant endpoints – safety (decreased bleeding risk with CSP), effectiveness (equivalent complete resection rates between CSP and HSP), and efficiency (CSP faster than HSP),” said Dr. Keswani, who wasn’t involved in the study.
Previous randomized controlled trials have shown that CSP is as effective as HSP but more efficient in removing small polyps. The reduction in delayed bleeding associated with CSP had been shown only in high-risk patients using antiplatelet agents or anticoagulants, however. Less was known about CSP’s effect on delayed bleeding in the general population.
To investigate, Dr. Chang and colleagues randomly assigned 4,270 adults aged 40 and older who were undergoing polypectomy to remove polyps measuring 4-10 mm to CSP or HSP.
Compared with HSP, CSP was associated with a significantly lower risk for all delayed bleeding (within 14 days after polypectomy) and severe delayed bleeding (defined as a decrease in hemoglobin of 20 g/L or more, requiring transfusion or hemostasis).
Eight of 2,137 patients (0.4%) in the CSP group had delayed bleeding versus 31 of 2,133 patients (1.5%) in the HSP group. Severe bleeding occurred in one patient who had CSP (0.05%) and eight who had HSP (0.4%).
The CSP group also had fewer emergency service visits than the HSP group – 4 visits (0.2%) versus 13 visits (0.6%).
CSP was more efficient, with mean polypectomy time reduced 26.9%, compared with HSP, with no difference between groups in successful tissue retrieval, en bloc resection, and complete histologic resection.
“CSP saves time setting up electrosurgical generators or conducting submucosal injection. Moreover, the lower rate of delayed bleeding means fewer emergency service visits or hospital stays, saving medical expenses,” Dr. Chang and colleagues write in their article.
“Given the benefit in safety and cost-effectiveness, CSP may replace HSP for removal of small polyps in the general population,” they add.
Dr. Keswani agreed. “Based on the accumulated evidence over the past decade, CSP is the clear standard of care for polyps 4-10 mm in size,” he said in an interview.
“For polyps less than 4 mm, it remains reasonable to use either large capacity/jumbo forceps or CSP. Cautery should be reserved only for polyps greater than 10 mm, although there is ongoing work regarding cold versus hot EMR [endoscopic mucosal resection],” Dr. Keswani said.
The trial was principal investigator–initiated and partially funded by Boston Scientific, which had no role in the study design, data collection or analysis, data interpretation, manuscript preparation, or decision to submit the manuscript for publication. Dr. Keswani is a consultant for Boston Scientific and Neptune Medical and receives research support from Virgo.
A version of this article first appeared on Medscape.com.
In the Taiwan Cold Polypectomy Study, CSP was not only safer than HSP, with a significantly lower risk for delayed bleeding, it was also more efficient, report Li-Chun Chang, MD, PhD, from the National Taiwan University Hospital, Taipei, and colleagues.
The study was published online in Annals of Internal Medicine.
This large study “strengthens the already significant evidence that CSP is as effective and safer than HSP for polyps 4-10 mm in size,” Rajesh N. Keswani, MD, Northwestern University, Chicago, told this news organization.
“This study evaluated all significant endpoints – safety (decreased bleeding risk with CSP), effectiveness (equivalent complete resection rates between CSP and HSP), and efficiency (CSP faster than HSP),” said Dr. Keswani, who wasn’t involved in the study.
Previous randomized controlled trials have shown that CSP is as effective as HSP but more efficient in removing small polyps. The reduction in delayed bleeding associated with CSP had been shown only in high-risk patients using antiplatelet agents or anticoagulants, however. Less was known about CSP’s effect on delayed bleeding in the general population.
To investigate, Dr. Chang and colleagues randomly assigned 4,270 adults aged 40 and older who were undergoing polypectomy to remove polyps measuring 4-10 mm to CSP or HSP.
Compared with HSP, CSP was associated with a significantly lower risk for all delayed bleeding (within 14 days after polypectomy) and severe delayed bleeding (defined as a decrease in hemoglobin of 20 g/L or more, requiring transfusion or hemostasis).
Eight of 2,137 patients (0.4%) in the CSP group had delayed bleeding versus 31 of 2,133 patients (1.5%) in the HSP group. Severe bleeding occurred in one patient who had CSP (0.05%) and eight who had HSP (0.4%).
The CSP group also had fewer emergency service visits than the HSP group – 4 visits (0.2%) versus 13 visits (0.6%).
CSP was more efficient, with mean polypectomy time reduced 26.9%, compared with HSP, with no difference between groups in successful tissue retrieval, en bloc resection, and complete histologic resection.
“CSP saves time setting up electrosurgical generators or conducting submucosal injection. Moreover, the lower rate of delayed bleeding means fewer emergency service visits or hospital stays, saving medical expenses,” Dr. Chang and colleagues write in their article.
“Given the benefit in safety and cost-effectiveness, CSP may replace HSP for removal of small polyps in the general population,” they add.
Dr. Keswani agreed. “Based on the accumulated evidence over the past decade, CSP is the clear standard of care for polyps 4-10 mm in size,” he said in an interview.
“For polyps less than 4 mm, it remains reasonable to use either large capacity/jumbo forceps or CSP. Cautery should be reserved only for polyps greater than 10 mm, although there is ongoing work regarding cold versus hot EMR [endoscopic mucosal resection],” Dr. Keswani said.
The trial was principal investigator–initiated and partially funded by Boston Scientific, which had no role in the study design, data collection or analysis, data interpretation, manuscript preparation, or decision to submit the manuscript for publication. Dr. Keswani is a consultant for Boston Scientific and Neptune Medical and receives research support from Virgo.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
‘Quick, affordable’ test helps predict CGRP response for migraine
new research suggests.
The ictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive massive nociceptive input from active meningeal nociceptors,” whereas the nonictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive no or subliminal nociceptive input from meningeal nociceptors,” investigators noted.
In an observational, open-label cohort study, pretreatment nonictal cephalic allodynia identified galcanezumab responders with nearly 80% accuracy, and it identified nonresponders with nearly 85% accuracy.
“Detection of nonictal allodynia with a simplified paradigm of Quantitative Sensory Testing (QST) may provide a quick, affordable, noninvasive, and patient-friendly way to prospectively distinguish between responders and nonresponders to the prophylactic treatment of chronic and high-frequency episodic migraine with drugs that reduce CGRP signaling,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote.
The findings were published online in Cephalalgia.
Immediate clinical relevance
Investigator Rami Burstein, PhD, also with Beth Israel Deaconess Medical Center and Harvard Medical School, developed the concept of predicting response to anti-CGRP treatment by testing for the presence or absence of nonictal cephalic allodynia in collaboration with the company CGRP Diagnostics.
In 43 anti–CGRP-naive patients with migraine, the researchers used a simplified QST algorithm to determine the presence/absence of cephalic or extracephalic allodynia during the nonictal phase of migraine – defined as the period from less than 12 hours after a migraine attack to less than 12 hours before the next attack.
Patients were considered to have allodynia if heat pain thresholds were between 32° C and 40° C, if cold pain thresholds were between 32° C and 20° C, or if the mechanical pain was threshold was less than 60 g.
Using these strict criteria, pretreatment nonictal cephalic allodynia was a statistically significant predictor of response to anti-CGRP therapy. It was present in 84% of the 19 nonresponders and was absent in 79% of the 24 responders, for an overall accuracy rate of 86% (P < .0001).
Nonictal cephalic allodynia was “consistently” predictive of response for patients with chronic migraine as well as for those with high-frequency episodic migraine, the researchers reported.
In contrast, they noted that assessing nonictal extracephalic allodynia with QST missed nearly 50% of the patients with allodynia among the nonresponders (accuracy rate of 42%) and added little to the assessment of allodynia among the responders.
Mark Hasleton, PhD, CEO of CGRP Diagnostics, said in an interview that the study shows it’s possible to determine response to anti-CGRP therapy and to prescribe these medications to patients who are most likely to respond.
Dr. Hasleton, who was not personally involved with the current study, noted that pretreatment testing for nonictal cephalic allodynia may also allow for earlier prescription of anti-CGRP therapy and potentially dispense without the need for the current trial-and-error approach to prescribing. He noted that if one anti-CGRP fails the patient, it is highly likely that others will also fail.
Given the “very high correlation of the presence of nonictal cephalic allodynia in responders to galcanezumab, our recommendation would be to routinely pretest all potential anti-CGRP candidates prior to prescription,” he said.
End of trial-and-error prescribing
In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, said this research is “very noteworthy, moving us one step closer to predictive, precision medicine and away from the practice of trial-and-error prescribing.
“The trial-and-error approach to migraine management is daunting. These are very costly therapies, and when they don’t work, there is continued tremendous suffering and loss of quality of life for patients,” said Dr. Lakhan, who was not involved in the study.
He added that the failure of drugs to benefit individual patients “may lead to distrust of the health care provider” and to the system as a whole, which in turn could lead to less access to care for other conditions or for preventive measures.
“I envision a time when these predictive measures collectively (interictal allodynia, as in this study, plus biobehavioral data) will assist us neurologists in appropriately selecting migraine therapies,” Dr. Lakhan said.
“Beyond that, we will eventually test new therapies not in cells, animals, and even humans but in silico. In the very near future, we will have solutions tailored to not people suffering a disease but to you – an individual with a unique genetic, protein, physical, developmental, psychological, and behavioral makeup,” he added.
The study was funded in part by Eli Lilly, the National Institutes of Health, and the anesthesia department at Beth Israel Deaconess Medical Center. Galcanezumab was provided by Eli Lilly. Dr. Lakhan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
The ictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive massive nociceptive input from active meningeal nociceptors,” whereas the nonictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive no or subliminal nociceptive input from meningeal nociceptors,” investigators noted.
In an observational, open-label cohort study, pretreatment nonictal cephalic allodynia identified galcanezumab responders with nearly 80% accuracy, and it identified nonresponders with nearly 85% accuracy.
“Detection of nonictal allodynia with a simplified paradigm of Quantitative Sensory Testing (QST) may provide a quick, affordable, noninvasive, and patient-friendly way to prospectively distinguish between responders and nonresponders to the prophylactic treatment of chronic and high-frequency episodic migraine with drugs that reduce CGRP signaling,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote.
The findings were published online in Cephalalgia.
Immediate clinical relevance
Investigator Rami Burstein, PhD, also with Beth Israel Deaconess Medical Center and Harvard Medical School, developed the concept of predicting response to anti-CGRP treatment by testing for the presence or absence of nonictal cephalic allodynia in collaboration with the company CGRP Diagnostics.
In 43 anti–CGRP-naive patients with migraine, the researchers used a simplified QST algorithm to determine the presence/absence of cephalic or extracephalic allodynia during the nonictal phase of migraine – defined as the period from less than 12 hours after a migraine attack to less than 12 hours before the next attack.
Patients were considered to have allodynia if heat pain thresholds were between 32° C and 40° C, if cold pain thresholds were between 32° C and 20° C, or if the mechanical pain was threshold was less than 60 g.
Using these strict criteria, pretreatment nonictal cephalic allodynia was a statistically significant predictor of response to anti-CGRP therapy. It was present in 84% of the 19 nonresponders and was absent in 79% of the 24 responders, for an overall accuracy rate of 86% (P < .0001).
Nonictal cephalic allodynia was “consistently” predictive of response for patients with chronic migraine as well as for those with high-frequency episodic migraine, the researchers reported.
In contrast, they noted that assessing nonictal extracephalic allodynia with QST missed nearly 50% of the patients with allodynia among the nonresponders (accuracy rate of 42%) and added little to the assessment of allodynia among the responders.
Mark Hasleton, PhD, CEO of CGRP Diagnostics, said in an interview that the study shows it’s possible to determine response to anti-CGRP therapy and to prescribe these medications to patients who are most likely to respond.
Dr. Hasleton, who was not personally involved with the current study, noted that pretreatment testing for nonictal cephalic allodynia may also allow for earlier prescription of anti-CGRP therapy and potentially dispense without the need for the current trial-and-error approach to prescribing. He noted that if one anti-CGRP fails the patient, it is highly likely that others will also fail.
Given the “very high correlation of the presence of nonictal cephalic allodynia in responders to galcanezumab, our recommendation would be to routinely pretest all potential anti-CGRP candidates prior to prescription,” he said.
End of trial-and-error prescribing
In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, said this research is “very noteworthy, moving us one step closer to predictive, precision medicine and away from the practice of trial-and-error prescribing.
“The trial-and-error approach to migraine management is daunting. These are very costly therapies, and when they don’t work, there is continued tremendous suffering and loss of quality of life for patients,” said Dr. Lakhan, who was not involved in the study.
He added that the failure of drugs to benefit individual patients “may lead to distrust of the health care provider” and to the system as a whole, which in turn could lead to less access to care for other conditions or for preventive measures.
“I envision a time when these predictive measures collectively (interictal allodynia, as in this study, plus biobehavioral data) will assist us neurologists in appropriately selecting migraine therapies,” Dr. Lakhan said.
“Beyond that, we will eventually test new therapies not in cells, animals, and even humans but in silico. In the very near future, we will have solutions tailored to not people suffering a disease but to you – an individual with a unique genetic, protein, physical, developmental, psychological, and behavioral makeup,” he added.
The study was funded in part by Eli Lilly, the National Institutes of Health, and the anesthesia department at Beth Israel Deaconess Medical Center. Galcanezumab was provided by Eli Lilly. Dr. Lakhan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
The ictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive massive nociceptive input from active meningeal nociceptors,” whereas the nonictal phase refers to “sensitization occurring during a time when central trigeminovascular neurons receive no or subliminal nociceptive input from meningeal nociceptors,” investigators noted.
In an observational, open-label cohort study, pretreatment nonictal cephalic allodynia identified galcanezumab responders with nearly 80% accuracy, and it identified nonresponders with nearly 85% accuracy.
“Detection of nonictal allodynia with a simplified paradigm of Quantitative Sensory Testing (QST) may provide a quick, affordable, noninvasive, and patient-friendly way to prospectively distinguish between responders and nonresponders to the prophylactic treatment of chronic and high-frequency episodic migraine with drugs that reduce CGRP signaling,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote.
The findings were published online in Cephalalgia.
Immediate clinical relevance
Investigator Rami Burstein, PhD, also with Beth Israel Deaconess Medical Center and Harvard Medical School, developed the concept of predicting response to anti-CGRP treatment by testing for the presence or absence of nonictal cephalic allodynia in collaboration with the company CGRP Diagnostics.
In 43 anti–CGRP-naive patients with migraine, the researchers used a simplified QST algorithm to determine the presence/absence of cephalic or extracephalic allodynia during the nonictal phase of migraine – defined as the period from less than 12 hours after a migraine attack to less than 12 hours before the next attack.
Patients were considered to have allodynia if heat pain thresholds were between 32° C and 40° C, if cold pain thresholds were between 32° C and 20° C, or if the mechanical pain was threshold was less than 60 g.
Using these strict criteria, pretreatment nonictal cephalic allodynia was a statistically significant predictor of response to anti-CGRP therapy. It was present in 84% of the 19 nonresponders and was absent in 79% of the 24 responders, for an overall accuracy rate of 86% (P < .0001).
Nonictal cephalic allodynia was “consistently” predictive of response for patients with chronic migraine as well as for those with high-frequency episodic migraine, the researchers reported.
In contrast, they noted that assessing nonictal extracephalic allodynia with QST missed nearly 50% of the patients with allodynia among the nonresponders (accuracy rate of 42%) and added little to the assessment of allodynia among the responders.
Mark Hasleton, PhD, CEO of CGRP Diagnostics, said in an interview that the study shows it’s possible to determine response to anti-CGRP therapy and to prescribe these medications to patients who are most likely to respond.
Dr. Hasleton, who was not personally involved with the current study, noted that pretreatment testing for nonictal cephalic allodynia may also allow for earlier prescription of anti-CGRP therapy and potentially dispense without the need for the current trial-and-error approach to prescribing. He noted that if one anti-CGRP fails the patient, it is highly likely that others will also fail.
Given the “very high correlation of the presence of nonictal cephalic allodynia in responders to galcanezumab, our recommendation would be to routinely pretest all potential anti-CGRP candidates prior to prescription,” he said.
End of trial-and-error prescribing
In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, said this research is “very noteworthy, moving us one step closer to predictive, precision medicine and away from the practice of trial-and-error prescribing.
“The trial-and-error approach to migraine management is daunting. These are very costly therapies, and when they don’t work, there is continued tremendous suffering and loss of quality of life for patients,” said Dr. Lakhan, who was not involved in the study.
He added that the failure of drugs to benefit individual patients “may lead to distrust of the health care provider” and to the system as a whole, which in turn could lead to less access to care for other conditions or for preventive measures.
“I envision a time when these predictive measures collectively (interictal allodynia, as in this study, plus biobehavioral data) will assist us neurologists in appropriately selecting migraine therapies,” Dr. Lakhan said.
“Beyond that, we will eventually test new therapies not in cells, animals, and even humans but in silico. In the very near future, we will have solutions tailored to not people suffering a disease but to you – an individual with a unique genetic, protein, physical, developmental, psychological, and behavioral makeup,” he added.
The study was funded in part by Eli Lilly, the National Institutes of Health, and the anesthesia department at Beth Israel Deaconess Medical Center. Galcanezumab was provided by Eli Lilly. Dr. Lakhan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CEPHALALGIA