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FDA approves new indication for avapritinib
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.
The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.
The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.
The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).
Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.
“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.
A version of this article first appeared on Medscape.com.
Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.
We can reduce suicide with enforced treatment and eyesight supervision
The old man was restrained at the last moment from jumping off the hospital’s fifth floor atrium parapet. He was suffering from terminal cancer and had been racked with chronic, severe pain for months.
The consult recognized symptoms of depression arising from his continuous physical suffering, advising that a male aide be dispatched to sit with the man and that he be put on a regimen of 10 mg of methadone twice a day to alleviate the pain. The following day the man was calm; he no longer wanted to kill himself. He expressed a strong desire to go home, return to gardening, and to play with his grandchildren.
Most of the 47,000 suicides that occur in the United States every year are preventable.1 Our national policy on this front has been nothing short of an abject failure. The government implemented a system with limited effect on completed suicides – a telephone hotline. This hotline is not called by the most common suicide victims: male, old, and quiet.2
The consequences of this national policy disaster have been profound, resulting in the biggest loss of productive years of life for any fatal condition.3 The grief experienced by the families of those who commit suicide is far greater than normal bereavement: The cause of death of their loved ones was not an unfortunate accident or a disease, it was an intentional act, and families take it personally.
One of the greatest achievements of psychiatry during the 20th century was the lowering of suicide rates in prisons by 70% with no treatment, no additional staffing, and no additional expenditures of funds. Today if inmates threaten suicide, they are immediately placed under eyesight supervision by guards. The federal pamphlet that describes this protocol was published in 1995 and is freely available online.4
Half of all suicide attempts are made by individuals who are legally drunk.5 Watch them for 6 hours and then ask them if they want to kill themselves and the response will almost invariably be “Of course not,” with the risk of further attempts dissipating in step with their blood alcohol level. The best resources to provide this kind of intervention are responsible adult family members, at no cost to the government. Indeed, in many cases family supervision is superior to that provided by a locked psychiatric ward with three staff members chasing after 20 agitated people all night long. The one-on-one attention that a family member can provide is free as well as far more personal and insightful, and more sincerely caring.
Guarantees in the field of medicine are rare. But, one such guarantee is that after their mood has improved, 100% of people will be thankful that they did not hurt themselves.6 This means that successful treatment will prevent 100% of all suicides.7 Not all treatments are successful, but 95% can be.8 At autopsy, few successful suicide victims have psychiatric medications in their system.9 The urge to kill oneself might best be characterized as a temporary chemical alteration of the brain causing delusional thoughts, including the ultimate delusion that life is not worth living.10 This alteration suppresses the strongest, most fundamental urge of all, namely, the survival instinct.
We must overturn the catastrophic decision of the U.S. Supreme Court that requires the showing of a dangerous act and the holding of a trial employing at least three lawyers for involuntary commitment to be authorized. Rather, involuntary treatment is justified by medical necessity as determined by two licensed professionals with no conflicts of interest. It can be outpatient.
The Supreme Court’s decision in O’Connor v. Donaldson in 1975 remedied an illusory wrong, addressing an act of blatant malpractice, not policy inequity.11 The superintendent of the state facility in that case was not even a doctor. He kept O’Connor prisoner for more than a decade, perhaps to keep a bed filled. Over the past half-century, this one decision has resulted in 1 million preventable suicides12 and half a million senseless murders by paranoid individuals, including many rampage shootings.13
More than two-thirds of homeless individuals suffer from an untreated mental condition.14 The vast majority of them will refuse all offers of treatment because they also have anosognosia, a brain-based disorder causing denial of illness.15 By referring to these individuals as “homeless,” we are also lowering real estate values for a square block around where they happen to be camped out. That cost has never been calculated, but it is another real consequence of this devastating Supreme Court decision.16
Detractors and mental health rights activists may argue that individual rights cannot be infringed. In that case, those same detractors and mental health rights activists must take responsibility for the thousands of lives and billions of dollars in economic damage caused by their refusal to allow an effective solution to the suicide epidemic to be implemented. Enforced outpatient treatment by the U.S. Air Force dropped its suicide rate by 60%. As an unintended benefit, the murder rate dropped by 50%.17
It is high time we did so.
Dr. Behar is a psychiatrist in Lower Merion, Pa. He graduated from Hahnemann Medical College, Philadelphia, in 1975, and has had postgraduate training at SUNY Stony Brook, University of Iowa, the National Institute of Mental Health, and Columbia University. His practice focuses on difficult, treatment-resistant cases.
References
1. U.S. Centers for Disease Control and Prevention. Suicide Prevention. 2020.
2. Luoma JB et al. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002 Jun 1. doi: 10.1176/appi.ajp.159.6.909.
3. World Health Organization. Suicide. 2021 Jun 17.
4. National Institute of Corrections. Correctional suicide prevention: Policies and procedures. 1995.
5. Hufford MR. Alcohol and suicidal behavior. Clin Psychol Rev. 2001 Jul;21(5):797-811.
6. Stanley B and Brown GK. Safety planning intervention: A brief intervention to mitigate suicide risk. Cogn Behav Pract. 2012 May;19(2):256-64.
7. Ibid.
8. Brown GK and Jager-Hyman S. Evidence-based psychotherapies for suicide prevention: Future directions. Am J Prev Med. 2014 Sep;47(3 Suppl 2):S186-94.
9. Isometsä ET. Psychological autopsy studies – A review. Eur Psychiatry. 2001 Nov;16(7):379-85.
10. Van Orden KA et al. The interpersonal theory of suicide. Psychol Rev. 2010 Apr; 117(2):575-600.
11. O’Connor v. Donaldson, 422 U.S. 563 (1975).
12. Calculated based on annual suicide statistics from the CDC and the time elapsed since the Supreme Court decision in O’Connor v. Donaldson.
13. Metzl JM and MacLeish KT. Mental illness, mass shootings, and the politics of American firearms. Am J Public Health. 2015 Feb;105(2):240-9.
14. Fazel S et al. The prevalence of mental disorders among the homeless in western countries: Systematic review and meta-regression analysis. PLoS Med. 2008 Dec 2;5(12):e225.
15. Amador XF and David AS. (eds.) Insight and psychosis: Awareness of illness in schizophrenia and related disorders (2nd ed.). Oxford Univ Press. 2004.
16. Calculated based on the potential impact of homelessness on property values and the relationship between untreated mental illness and homelessness.
17. Armed Forces Health Surveillance Branch. Surveillance snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998-2015. Medical Surveillance Monthly Report. 2016 Apr;23(4):19.
The old man was restrained at the last moment from jumping off the hospital’s fifth floor atrium parapet. He was suffering from terminal cancer and had been racked with chronic, severe pain for months.
The consult recognized symptoms of depression arising from his continuous physical suffering, advising that a male aide be dispatched to sit with the man and that he be put on a regimen of 10 mg of methadone twice a day to alleviate the pain. The following day the man was calm; he no longer wanted to kill himself. He expressed a strong desire to go home, return to gardening, and to play with his grandchildren.
Most of the 47,000 suicides that occur in the United States every year are preventable.1 Our national policy on this front has been nothing short of an abject failure. The government implemented a system with limited effect on completed suicides – a telephone hotline. This hotline is not called by the most common suicide victims: male, old, and quiet.2
The consequences of this national policy disaster have been profound, resulting in the biggest loss of productive years of life for any fatal condition.3 The grief experienced by the families of those who commit suicide is far greater than normal bereavement: The cause of death of their loved ones was not an unfortunate accident or a disease, it was an intentional act, and families take it personally.
One of the greatest achievements of psychiatry during the 20th century was the lowering of suicide rates in prisons by 70% with no treatment, no additional staffing, and no additional expenditures of funds. Today if inmates threaten suicide, they are immediately placed under eyesight supervision by guards. The federal pamphlet that describes this protocol was published in 1995 and is freely available online.4
Half of all suicide attempts are made by individuals who are legally drunk.5 Watch them for 6 hours and then ask them if they want to kill themselves and the response will almost invariably be “Of course not,” with the risk of further attempts dissipating in step with their blood alcohol level. The best resources to provide this kind of intervention are responsible adult family members, at no cost to the government. Indeed, in many cases family supervision is superior to that provided by a locked psychiatric ward with three staff members chasing after 20 agitated people all night long. The one-on-one attention that a family member can provide is free as well as far more personal and insightful, and more sincerely caring.
Guarantees in the field of medicine are rare. But, one such guarantee is that after their mood has improved, 100% of people will be thankful that they did not hurt themselves.6 This means that successful treatment will prevent 100% of all suicides.7 Not all treatments are successful, but 95% can be.8 At autopsy, few successful suicide victims have psychiatric medications in their system.9 The urge to kill oneself might best be characterized as a temporary chemical alteration of the brain causing delusional thoughts, including the ultimate delusion that life is not worth living.10 This alteration suppresses the strongest, most fundamental urge of all, namely, the survival instinct.
We must overturn the catastrophic decision of the U.S. Supreme Court that requires the showing of a dangerous act and the holding of a trial employing at least three lawyers for involuntary commitment to be authorized. Rather, involuntary treatment is justified by medical necessity as determined by two licensed professionals with no conflicts of interest. It can be outpatient.
The Supreme Court’s decision in O’Connor v. Donaldson in 1975 remedied an illusory wrong, addressing an act of blatant malpractice, not policy inequity.11 The superintendent of the state facility in that case was not even a doctor. He kept O’Connor prisoner for more than a decade, perhaps to keep a bed filled. Over the past half-century, this one decision has resulted in 1 million preventable suicides12 and half a million senseless murders by paranoid individuals, including many rampage shootings.13
More than two-thirds of homeless individuals suffer from an untreated mental condition.14 The vast majority of them will refuse all offers of treatment because they also have anosognosia, a brain-based disorder causing denial of illness.15 By referring to these individuals as “homeless,” we are also lowering real estate values for a square block around where they happen to be camped out. That cost has never been calculated, but it is another real consequence of this devastating Supreme Court decision.16
Detractors and mental health rights activists may argue that individual rights cannot be infringed. In that case, those same detractors and mental health rights activists must take responsibility for the thousands of lives and billions of dollars in economic damage caused by their refusal to allow an effective solution to the suicide epidemic to be implemented. Enforced outpatient treatment by the U.S. Air Force dropped its suicide rate by 60%. As an unintended benefit, the murder rate dropped by 50%.17
It is high time we did so.
Dr. Behar is a psychiatrist in Lower Merion, Pa. He graduated from Hahnemann Medical College, Philadelphia, in 1975, and has had postgraduate training at SUNY Stony Brook, University of Iowa, the National Institute of Mental Health, and Columbia University. His practice focuses on difficult, treatment-resistant cases.
References
1. U.S. Centers for Disease Control and Prevention. Suicide Prevention. 2020.
2. Luoma JB et al. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002 Jun 1. doi: 10.1176/appi.ajp.159.6.909.
3. World Health Organization. Suicide. 2021 Jun 17.
4. National Institute of Corrections. Correctional suicide prevention: Policies and procedures. 1995.
5. Hufford MR. Alcohol and suicidal behavior. Clin Psychol Rev. 2001 Jul;21(5):797-811.
6. Stanley B and Brown GK. Safety planning intervention: A brief intervention to mitigate suicide risk. Cogn Behav Pract. 2012 May;19(2):256-64.
7. Ibid.
8. Brown GK and Jager-Hyman S. Evidence-based psychotherapies for suicide prevention: Future directions. Am J Prev Med. 2014 Sep;47(3 Suppl 2):S186-94.
9. Isometsä ET. Psychological autopsy studies – A review. Eur Psychiatry. 2001 Nov;16(7):379-85.
10. Van Orden KA et al. The interpersonal theory of suicide. Psychol Rev. 2010 Apr; 117(2):575-600.
11. O’Connor v. Donaldson, 422 U.S. 563 (1975).
12. Calculated based on annual suicide statistics from the CDC and the time elapsed since the Supreme Court decision in O’Connor v. Donaldson.
13. Metzl JM and MacLeish KT. Mental illness, mass shootings, and the politics of American firearms. Am J Public Health. 2015 Feb;105(2):240-9.
14. Fazel S et al. The prevalence of mental disorders among the homeless in western countries: Systematic review and meta-regression analysis. PLoS Med. 2008 Dec 2;5(12):e225.
15. Amador XF and David AS. (eds.) Insight and psychosis: Awareness of illness in schizophrenia and related disorders (2nd ed.). Oxford Univ Press. 2004.
16. Calculated based on the potential impact of homelessness on property values and the relationship between untreated mental illness and homelessness.
17. Armed Forces Health Surveillance Branch. Surveillance snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998-2015. Medical Surveillance Monthly Report. 2016 Apr;23(4):19.
The old man was restrained at the last moment from jumping off the hospital’s fifth floor atrium parapet. He was suffering from terminal cancer and had been racked with chronic, severe pain for months.
The consult recognized symptoms of depression arising from his continuous physical suffering, advising that a male aide be dispatched to sit with the man and that he be put on a regimen of 10 mg of methadone twice a day to alleviate the pain. The following day the man was calm; he no longer wanted to kill himself. He expressed a strong desire to go home, return to gardening, and to play with his grandchildren.
Most of the 47,000 suicides that occur in the United States every year are preventable.1 Our national policy on this front has been nothing short of an abject failure. The government implemented a system with limited effect on completed suicides – a telephone hotline. This hotline is not called by the most common suicide victims: male, old, and quiet.2
The consequences of this national policy disaster have been profound, resulting in the biggest loss of productive years of life for any fatal condition.3 The grief experienced by the families of those who commit suicide is far greater than normal bereavement: The cause of death of their loved ones was not an unfortunate accident or a disease, it was an intentional act, and families take it personally.
One of the greatest achievements of psychiatry during the 20th century was the lowering of suicide rates in prisons by 70% with no treatment, no additional staffing, and no additional expenditures of funds. Today if inmates threaten suicide, they are immediately placed under eyesight supervision by guards. The federal pamphlet that describes this protocol was published in 1995 and is freely available online.4
Half of all suicide attempts are made by individuals who are legally drunk.5 Watch them for 6 hours and then ask them if they want to kill themselves and the response will almost invariably be “Of course not,” with the risk of further attempts dissipating in step with their blood alcohol level. The best resources to provide this kind of intervention are responsible adult family members, at no cost to the government. Indeed, in many cases family supervision is superior to that provided by a locked psychiatric ward with three staff members chasing after 20 agitated people all night long. The one-on-one attention that a family member can provide is free as well as far more personal and insightful, and more sincerely caring.
Guarantees in the field of medicine are rare. But, one such guarantee is that after their mood has improved, 100% of people will be thankful that they did not hurt themselves.6 This means that successful treatment will prevent 100% of all suicides.7 Not all treatments are successful, but 95% can be.8 At autopsy, few successful suicide victims have psychiatric medications in their system.9 The urge to kill oneself might best be characterized as a temporary chemical alteration of the brain causing delusional thoughts, including the ultimate delusion that life is not worth living.10 This alteration suppresses the strongest, most fundamental urge of all, namely, the survival instinct.
We must overturn the catastrophic decision of the U.S. Supreme Court that requires the showing of a dangerous act and the holding of a trial employing at least three lawyers for involuntary commitment to be authorized. Rather, involuntary treatment is justified by medical necessity as determined by two licensed professionals with no conflicts of interest. It can be outpatient.
The Supreme Court’s decision in O’Connor v. Donaldson in 1975 remedied an illusory wrong, addressing an act of blatant malpractice, not policy inequity.11 The superintendent of the state facility in that case was not even a doctor. He kept O’Connor prisoner for more than a decade, perhaps to keep a bed filled. Over the past half-century, this one decision has resulted in 1 million preventable suicides12 and half a million senseless murders by paranoid individuals, including many rampage shootings.13
More than two-thirds of homeless individuals suffer from an untreated mental condition.14 The vast majority of them will refuse all offers of treatment because they also have anosognosia, a brain-based disorder causing denial of illness.15 By referring to these individuals as “homeless,” we are also lowering real estate values for a square block around where they happen to be camped out. That cost has never been calculated, but it is another real consequence of this devastating Supreme Court decision.16
Detractors and mental health rights activists may argue that individual rights cannot be infringed. In that case, those same detractors and mental health rights activists must take responsibility for the thousands of lives and billions of dollars in economic damage caused by their refusal to allow an effective solution to the suicide epidemic to be implemented. Enforced outpatient treatment by the U.S. Air Force dropped its suicide rate by 60%. As an unintended benefit, the murder rate dropped by 50%.17
It is high time we did so.
Dr. Behar is a psychiatrist in Lower Merion, Pa. He graduated from Hahnemann Medical College, Philadelphia, in 1975, and has had postgraduate training at SUNY Stony Brook, University of Iowa, the National Institute of Mental Health, and Columbia University. His practice focuses on difficult, treatment-resistant cases.
References
1. U.S. Centers for Disease Control and Prevention. Suicide Prevention. 2020.
2. Luoma JB et al. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002 Jun 1. doi: 10.1176/appi.ajp.159.6.909.
3. World Health Organization. Suicide. 2021 Jun 17.
4. National Institute of Corrections. Correctional suicide prevention: Policies and procedures. 1995.
5. Hufford MR. Alcohol and suicidal behavior. Clin Psychol Rev. 2001 Jul;21(5):797-811.
6. Stanley B and Brown GK. Safety planning intervention: A brief intervention to mitigate suicide risk. Cogn Behav Pract. 2012 May;19(2):256-64.
7. Ibid.
8. Brown GK and Jager-Hyman S. Evidence-based psychotherapies for suicide prevention: Future directions. Am J Prev Med. 2014 Sep;47(3 Suppl 2):S186-94.
9. Isometsä ET. Psychological autopsy studies – A review. Eur Psychiatry. 2001 Nov;16(7):379-85.
10. Van Orden KA et al. The interpersonal theory of suicide. Psychol Rev. 2010 Apr; 117(2):575-600.
11. O’Connor v. Donaldson, 422 U.S. 563 (1975).
12. Calculated based on annual suicide statistics from the CDC and the time elapsed since the Supreme Court decision in O’Connor v. Donaldson.
13. Metzl JM and MacLeish KT. Mental illness, mass shootings, and the politics of American firearms. Am J Public Health. 2015 Feb;105(2):240-9.
14. Fazel S et al. The prevalence of mental disorders among the homeless in western countries: Systematic review and meta-regression analysis. PLoS Med. 2008 Dec 2;5(12):e225.
15. Amador XF and David AS. (eds.) Insight and psychosis: Awareness of illness in schizophrenia and related disorders (2nd ed.). Oxford Univ Press. 2004.
16. Calculated based on the potential impact of homelessness on property values and the relationship between untreated mental illness and homelessness.
17. Armed Forces Health Surveillance Branch. Surveillance snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998-2015. Medical Surveillance Monthly Report. 2016 Apr;23(4):19.
Which interventions could lessen the burden of dementia?
Using a microsimulation algorithm that accounts for the effect on mortality, a team from Marseille, France, has shown that interventions targeting the three main vascular risk factors for dementia – hypertension, diabetes, and physical inactivity – could significantly reduce the burden of dementia by 2040.
Although these modeling results could appear too optimistic, since total disappearance of the risk factors was assumed, the authors say the results do show that targeted interventions for these factors could be effective in reducing the future burden of dementia.
Increasing prevalence
According to the World Alzheimer Report 2018, 50 million people around the world were living with dementia; a population roughly around the size of South Korea or Spain. That community is likely to rise to about 152 million people by 2050, which is similar to the size of Russia or Bangladesh, the result of an aging population.
Among modifiable risk factors, many studies support a deleterious effect of hypertension, diabetes, and physical inactivity on the risk of dementia. However, since the distribution of these risk factors could have a direct impact on mortality, reducing it should increase life expectancy and the number of cases of dementia.
The team, headed by Hélène Jacqmin-Gadda, PhD, research director at the University of Bordeaux (France), has developed a microsimulation model capable of predicting the burden of dementia while accounting for the impact on mortality. The team used this approach to assess the impact of interventions targeting these three main risk factors on the burden of dementia in France by 2040.
Removing risk factors
The researchers estimated the incidence of dementia for men and women using data from the 2020 PAQUID cohort, and these data were combined with the projections forecast by the French National Institute of Statistics and Economic Studies to account for mortality with and without dementia.
Without intervention, the prevalence rate of dementia in 2040 would be 9.6% among men and 14% among women older than 65 years.
These figures would decrease to 6.4% (−33%) and 10.4% (−26%), respectively, under the intervention scenario whereby the three modifiable vascular risk factors (hypertension, diabetes, and physical inactivity) would be removed simultaneously beginning in 2020. The prevalence rates are significantly reduced for men and women from age 75 years. In this scenario, life expectancy without dementia would increase by 3.4 years in men and 2.6 years in women, the result of men being more exposed to these three risk factors.
Other scenarios have estimated dementia prevalence with the disappearance of just one of these risk factors. For example, the disappearance of hypertension alone from 2020 could decrease dementia prevalence by 21% in men and 16% in women (because this risk factor is less common in women than in men) by 2040. This reduction would be associated with a decrease in the lifelong probability of dementia among men and women and a gain in life expectancy without dementia of 2 years in men and 1.4 years in women.
Among the three factors, hypertension has the largest impact on dementia burden in the French population, since this is, by far, the most prevalent (69% in men and 49% in women), while intervention targeting only diabetes or physical inactivity would lead to a reduction in dementia prevalence of only 4%-7%.
The authors reported no conflicts of interest.
This article was translated from Univadis France. A version appeared on Medscape.com.
Using a microsimulation algorithm that accounts for the effect on mortality, a team from Marseille, France, has shown that interventions targeting the three main vascular risk factors for dementia – hypertension, diabetes, and physical inactivity – could significantly reduce the burden of dementia by 2040.
Although these modeling results could appear too optimistic, since total disappearance of the risk factors was assumed, the authors say the results do show that targeted interventions for these factors could be effective in reducing the future burden of dementia.
Increasing prevalence
According to the World Alzheimer Report 2018, 50 million people around the world were living with dementia; a population roughly around the size of South Korea or Spain. That community is likely to rise to about 152 million people by 2050, which is similar to the size of Russia or Bangladesh, the result of an aging population.
Among modifiable risk factors, many studies support a deleterious effect of hypertension, diabetes, and physical inactivity on the risk of dementia. However, since the distribution of these risk factors could have a direct impact on mortality, reducing it should increase life expectancy and the number of cases of dementia.
The team, headed by Hélène Jacqmin-Gadda, PhD, research director at the University of Bordeaux (France), has developed a microsimulation model capable of predicting the burden of dementia while accounting for the impact on mortality. The team used this approach to assess the impact of interventions targeting these three main risk factors on the burden of dementia in France by 2040.
Removing risk factors
The researchers estimated the incidence of dementia for men and women using data from the 2020 PAQUID cohort, and these data were combined with the projections forecast by the French National Institute of Statistics and Economic Studies to account for mortality with and without dementia.
Without intervention, the prevalence rate of dementia in 2040 would be 9.6% among men and 14% among women older than 65 years.
These figures would decrease to 6.4% (−33%) and 10.4% (−26%), respectively, under the intervention scenario whereby the three modifiable vascular risk factors (hypertension, diabetes, and physical inactivity) would be removed simultaneously beginning in 2020. The prevalence rates are significantly reduced for men and women from age 75 years. In this scenario, life expectancy without dementia would increase by 3.4 years in men and 2.6 years in women, the result of men being more exposed to these three risk factors.
Other scenarios have estimated dementia prevalence with the disappearance of just one of these risk factors. For example, the disappearance of hypertension alone from 2020 could decrease dementia prevalence by 21% in men and 16% in women (because this risk factor is less common in women than in men) by 2040. This reduction would be associated with a decrease in the lifelong probability of dementia among men and women and a gain in life expectancy without dementia of 2 years in men and 1.4 years in women.
Among the three factors, hypertension has the largest impact on dementia burden in the French population, since this is, by far, the most prevalent (69% in men and 49% in women), while intervention targeting only diabetes or physical inactivity would lead to a reduction in dementia prevalence of only 4%-7%.
The authors reported no conflicts of interest.
This article was translated from Univadis France. A version appeared on Medscape.com.
Using a microsimulation algorithm that accounts for the effect on mortality, a team from Marseille, France, has shown that interventions targeting the three main vascular risk factors for dementia – hypertension, diabetes, and physical inactivity – could significantly reduce the burden of dementia by 2040.
Although these modeling results could appear too optimistic, since total disappearance of the risk factors was assumed, the authors say the results do show that targeted interventions for these factors could be effective in reducing the future burden of dementia.
Increasing prevalence
According to the World Alzheimer Report 2018, 50 million people around the world were living with dementia; a population roughly around the size of South Korea or Spain. That community is likely to rise to about 152 million people by 2050, which is similar to the size of Russia or Bangladesh, the result of an aging population.
Among modifiable risk factors, many studies support a deleterious effect of hypertension, diabetes, and physical inactivity on the risk of dementia. However, since the distribution of these risk factors could have a direct impact on mortality, reducing it should increase life expectancy and the number of cases of dementia.
The team, headed by Hélène Jacqmin-Gadda, PhD, research director at the University of Bordeaux (France), has developed a microsimulation model capable of predicting the burden of dementia while accounting for the impact on mortality. The team used this approach to assess the impact of interventions targeting these three main risk factors on the burden of dementia in France by 2040.
Removing risk factors
The researchers estimated the incidence of dementia for men and women using data from the 2020 PAQUID cohort, and these data were combined with the projections forecast by the French National Institute of Statistics and Economic Studies to account for mortality with and without dementia.
Without intervention, the prevalence rate of dementia in 2040 would be 9.6% among men and 14% among women older than 65 years.
These figures would decrease to 6.4% (−33%) and 10.4% (−26%), respectively, under the intervention scenario whereby the three modifiable vascular risk factors (hypertension, diabetes, and physical inactivity) would be removed simultaneously beginning in 2020. The prevalence rates are significantly reduced for men and women from age 75 years. In this scenario, life expectancy without dementia would increase by 3.4 years in men and 2.6 years in women, the result of men being more exposed to these three risk factors.
Other scenarios have estimated dementia prevalence with the disappearance of just one of these risk factors. For example, the disappearance of hypertension alone from 2020 could decrease dementia prevalence by 21% in men and 16% in women (because this risk factor is less common in women than in men) by 2040. This reduction would be associated with a decrease in the lifelong probability of dementia among men and women and a gain in life expectancy without dementia of 2 years in men and 1.4 years in women.
Among the three factors, hypertension has the largest impact on dementia burden in the French population, since this is, by far, the most prevalent (69% in men and 49% in women), while intervention targeting only diabetes or physical inactivity would lead to a reduction in dementia prevalence of only 4%-7%.
The authors reported no conflicts of interest.
This article was translated from Univadis France. A version appeared on Medscape.com.
FROM THE EUROPEAN JOURNAL OF EPIDEMIOLOGY
Scheduled bleeding may boost tolerability of hormone implants
BALTIMORE – The bleeding causes some women to have the device removed, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
In a randomized, double-blinded, placebo-controlled trial of 51 patients desiring the implants – which suppress ovulation by releasing progestin over a 3-year period – taking norethindrone acetate for 1 week every 4 weeks led to 80% of participants in the treatment group reporting satisfactory bleeding patterns with the etonogestrel implants in place.
Rates of early discontinuation have been variable, according to published literature, ranging from 13% to 21.1%, said Jordan Gray, MD, a fourth-year resident in ob.gyn. at Baylor Scott and White Medical Center, Temple, Tex., who helped conduct the new study. Reasons included bothersome bleeding. Dr. Gray and colleagues found that 24% of women in the placebo group requested removal of the implant, compared with 9% of those in the treatment group. Among these women, none requested removal for bothersome bleeding but rather for reasons such as wanting to get pregnant. One person requested removal because she did not like amenorrhea.
While the results of the study did not achieve statistical significance, owing to its size and noncompliance among some participants, it does indicate that norethindrone acetate may be helpful, Dr. Gray said.
During the study, participants in the treatment group (n = 22) received a monthly treatment regimen of 5 mg of oral norethindrone acetate daily for 7 days each month for the first 6 months after placement of an etonogestrel implant. The placebo group (n = 29) was given inert tablets prescribed in the same regimen. Both groups received products from a mail-order pharmacy.
Participants were women aged 18-48 years who desired an implant or those aged 14 years who had permission from a parent or guardian to receive the contraceptive. The study excluded people with known or suspected pregnancy, those less than 8 weeks’ post partum, those who experienced menarche less than 2 years ago, those with body mass index greater than 40, and those who received depot medroxyprogesterone acetate within the previous 12 weeks. Excessive bleeding was defined as bleeding or spotting on more than 7 consecutive days or a fifth episode of bleeding in 90 days.
Overall, 11 patients (38%) in the placebo group and 10 (45%) in the treatment arm withdrew from the study. Reasons included wanting to get pregnant, mood changes, or noncompliance with study parameters, which included not responding or returning bleeding diaries, Dr. Gray said.
A limitation of the study was that compliance was less than expected. In addition, there were challenges with rates of responses, Dr. Gray said. The study was conducted during the COVID-19 pandemic, when all in-person visits were transitioned to telehealth. Although the investigators offered payment to participants, not all returned text-message surveys. The researchers had intended to enroll 124 participants but curtailed the study early, owing to the limited number of participants.
Given that there is no standard approach to treating prolonged or excessive bleeding with etonogestrel implants, Dr. Gray said, “Our data suggests that this regimen is a simple and acceptable method to treat bothersome bleeding and that predictable bleeding may be more satisfactory than unpredictable bleeding.”
Veronica Maria Pimentel, MD, moderator of the session and a maternal-fetal medicine specialist and director of research for the ob.gyn. residency program at St. Francis Hospital, part of Trinity Health of New England in Hartford, Conn., praised the researchers for a well-designed study.
“However, unfortunately, they were not able to recruit the number of patients that they needed in order to achieve the power to show the difference [between treatment arms], so another study would have to be done to show if there is a difference,” Dr. Pimentel said.
Dr. Pimentel complimented Dr. Gray following her presentation, congratulating her for conducting a randomized, controlled trial: “That’s not easy, as you have shown, but it’s also a good try, so you can actually see how hard it is to obtain quality data from research.”
The study was supported in part by a research grant from the Investigator-Initiated Studies Program of Organon. Dr. Gray is a consultant for Johnson & Johnson. Dr. Pimentel has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BALTIMORE – The bleeding causes some women to have the device removed, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
In a randomized, double-blinded, placebo-controlled trial of 51 patients desiring the implants – which suppress ovulation by releasing progestin over a 3-year period – taking norethindrone acetate for 1 week every 4 weeks led to 80% of participants in the treatment group reporting satisfactory bleeding patterns with the etonogestrel implants in place.
Rates of early discontinuation have been variable, according to published literature, ranging from 13% to 21.1%, said Jordan Gray, MD, a fourth-year resident in ob.gyn. at Baylor Scott and White Medical Center, Temple, Tex., who helped conduct the new study. Reasons included bothersome bleeding. Dr. Gray and colleagues found that 24% of women in the placebo group requested removal of the implant, compared with 9% of those in the treatment group. Among these women, none requested removal for bothersome bleeding but rather for reasons such as wanting to get pregnant. One person requested removal because she did not like amenorrhea.
While the results of the study did not achieve statistical significance, owing to its size and noncompliance among some participants, it does indicate that norethindrone acetate may be helpful, Dr. Gray said.
During the study, participants in the treatment group (n = 22) received a monthly treatment regimen of 5 mg of oral norethindrone acetate daily for 7 days each month for the first 6 months after placement of an etonogestrel implant. The placebo group (n = 29) was given inert tablets prescribed in the same regimen. Both groups received products from a mail-order pharmacy.
Participants were women aged 18-48 years who desired an implant or those aged 14 years who had permission from a parent or guardian to receive the contraceptive. The study excluded people with known or suspected pregnancy, those less than 8 weeks’ post partum, those who experienced menarche less than 2 years ago, those with body mass index greater than 40, and those who received depot medroxyprogesterone acetate within the previous 12 weeks. Excessive bleeding was defined as bleeding or spotting on more than 7 consecutive days or a fifth episode of bleeding in 90 days.
Overall, 11 patients (38%) in the placebo group and 10 (45%) in the treatment arm withdrew from the study. Reasons included wanting to get pregnant, mood changes, or noncompliance with study parameters, which included not responding or returning bleeding diaries, Dr. Gray said.
A limitation of the study was that compliance was less than expected. In addition, there were challenges with rates of responses, Dr. Gray said. The study was conducted during the COVID-19 pandemic, when all in-person visits were transitioned to telehealth. Although the investigators offered payment to participants, not all returned text-message surveys. The researchers had intended to enroll 124 participants but curtailed the study early, owing to the limited number of participants.
Given that there is no standard approach to treating prolonged or excessive bleeding with etonogestrel implants, Dr. Gray said, “Our data suggests that this regimen is a simple and acceptable method to treat bothersome bleeding and that predictable bleeding may be more satisfactory than unpredictable bleeding.”
Veronica Maria Pimentel, MD, moderator of the session and a maternal-fetal medicine specialist and director of research for the ob.gyn. residency program at St. Francis Hospital, part of Trinity Health of New England in Hartford, Conn., praised the researchers for a well-designed study.
“However, unfortunately, they were not able to recruit the number of patients that they needed in order to achieve the power to show the difference [between treatment arms], so another study would have to be done to show if there is a difference,” Dr. Pimentel said.
Dr. Pimentel complimented Dr. Gray following her presentation, congratulating her for conducting a randomized, controlled trial: “That’s not easy, as you have shown, but it’s also a good try, so you can actually see how hard it is to obtain quality data from research.”
The study was supported in part by a research grant from the Investigator-Initiated Studies Program of Organon. Dr. Gray is a consultant for Johnson & Johnson. Dr. Pimentel has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BALTIMORE – The bleeding causes some women to have the device removed, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
In a randomized, double-blinded, placebo-controlled trial of 51 patients desiring the implants – which suppress ovulation by releasing progestin over a 3-year period – taking norethindrone acetate for 1 week every 4 weeks led to 80% of participants in the treatment group reporting satisfactory bleeding patterns with the etonogestrel implants in place.
Rates of early discontinuation have been variable, according to published literature, ranging from 13% to 21.1%, said Jordan Gray, MD, a fourth-year resident in ob.gyn. at Baylor Scott and White Medical Center, Temple, Tex., who helped conduct the new study. Reasons included bothersome bleeding. Dr. Gray and colleagues found that 24% of women in the placebo group requested removal of the implant, compared with 9% of those in the treatment group. Among these women, none requested removal for bothersome bleeding but rather for reasons such as wanting to get pregnant. One person requested removal because she did not like amenorrhea.
While the results of the study did not achieve statistical significance, owing to its size and noncompliance among some participants, it does indicate that norethindrone acetate may be helpful, Dr. Gray said.
During the study, participants in the treatment group (n = 22) received a monthly treatment regimen of 5 mg of oral norethindrone acetate daily for 7 days each month for the first 6 months after placement of an etonogestrel implant. The placebo group (n = 29) was given inert tablets prescribed in the same regimen. Both groups received products from a mail-order pharmacy.
Participants were women aged 18-48 years who desired an implant or those aged 14 years who had permission from a parent or guardian to receive the contraceptive. The study excluded people with known or suspected pregnancy, those less than 8 weeks’ post partum, those who experienced menarche less than 2 years ago, those with body mass index greater than 40, and those who received depot medroxyprogesterone acetate within the previous 12 weeks. Excessive bleeding was defined as bleeding or spotting on more than 7 consecutive days or a fifth episode of bleeding in 90 days.
Overall, 11 patients (38%) in the placebo group and 10 (45%) in the treatment arm withdrew from the study. Reasons included wanting to get pregnant, mood changes, or noncompliance with study parameters, which included not responding or returning bleeding diaries, Dr. Gray said.
A limitation of the study was that compliance was less than expected. In addition, there were challenges with rates of responses, Dr. Gray said. The study was conducted during the COVID-19 pandemic, when all in-person visits were transitioned to telehealth. Although the investigators offered payment to participants, not all returned text-message surveys. The researchers had intended to enroll 124 participants but curtailed the study early, owing to the limited number of participants.
Given that there is no standard approach to treating prolonged or excessive bleeding with etonogestrel implants, Dr. Gray said, “Our data suggests that this regimen is a simple and acceptable method to treat bothersome bleeding and that predictable bleeding may be more satisfactory than unpredictable bleeding.”
Veronica Maria Pimentel, MD, moderator of the session and a maternal-fetal medicine specialist and director of research for the ob.gyn. residency program at St. Francis Hospital, part of Trinity Health of New England in Hartford, Conn., praised the researchers for a well-designed study.
“However, unfortunately, they were not able to recruit the number of patients that they needed in order to achieve the power to show the difference [between treatment arms], so another study would have to be done to show if there is a difference,” Dr. Pimentel said.
Dr. Pimentel complimented Dr. Gray following her presentation, congratulating her for conducting a randomized, controlled trial: “That’s not easy, as you have shown, but it’s also a good try, so you can actually see how hard it is to obtain quality data from research.”
The study was supported in part by a research grant from the Investigator-Initiated Studies Program of Organon. Dr. Gray is a consultant for Johnson & Johnson. Dr. Pimentel has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACOG 2023
Early remission in lupus nephritis can still progress to advanced CKD
SEOUL, SOUTH KOREA – Nearly 8% of people with lupus nephritis who achieve complete remission of disease within 1 year of starting treatment will still go on to develop advanced chronic kidney disease (CKD), according to a presentation at an international congress on systemic lupus erythematosus.
Rheumatologist Dafna Gladman, MD, professor of medicine at the University of Toronto and codirector of the Lupus Clinic at Toronto Western Hospital, showed data from the Lupus Clinic’s prospective longitudinal cohort study in 273 patients with confirmed lupus nephritis who achieved complete remission within 12 months of baseline.
Remission was defined as less than 0.5 g proteinuria over 24 hours, inactive urinary sediment, and serum creatinine less than 120% of baseline.
Of this group, 21 (7.7%) progressed to advanced CKD during follow-up, which ranged from 0.7 to 31.7 years with a median of 5.8 years, after enrollment.
Patients who had experienced at least one flare during their first 5 years were around 4.5 times more likely to progress to advanced CKD than were those who did not experience a flare.
While the study excluded patients who already had advanced CKD, the analysis found those with evidence of impaired kidney function at baseline also had more than a fourfold higher risk of developing advanced CKD.
Other significant risk factors for progression were having low complement C3 levels at baseline and having had a longer duration of disease before enrollment.
“Those patients already have abnormal renal function, so the message is that patients who are already in trouble, you’ve got to watch them very carefully,” Dr. Gladman said in an interview.
The study also looked at whether there was a difference between patients who developed advanced CKD earlier – before the median of 5.8 years – or later. While the numbers were small, Dr. Gladman said patients who progressed earlier tended to be older and were more likely to be on antihypertensive treatment and have lower estimated glomerular filtration rate and a lower Systemic Lupus Erythematosus Disease Activity Index–2K, compared with those who progressed later. Some patients also were noncompliant and/or experienced concomitant infections; four had moderate to severe interstitial fibrosis and tubular atrophy.
“We conclude that such patients should be monitored closely despite early remission, and we also highlight the importance of maintenance therapy, which should be communicated to the patients to prevent noncompliance and subsequent flare,” Dr. Gladman told the conference.
Dr. Gladman said her clinic told patients from the very beginning of their treatment that they would need to be seen at 2- to 6-month intervals, regardless of how well their disease was doing.
Commenting on the presentation, rheumatologist Mandana Nikpour MD, PhD, of St. Vincent’s Hospital in Melbourne, said the findings showed the importance of keeping a close eye on patients with lupus nephritis, even if their disease appears to be in remission.
“If you’ve had nephritis, and you go into remission, you may already have a degree of damage in your kidneys,” said Dr. Nikpour, also from the University of Melbourne. “If there’s a degree of uncontrolled hypertension, or if a patient is noncompliant with their treatment, and there’s a degree of grumbling disease activity, that can all conspire and add up to result in long-term kidney damage and loss of renal function.”
Dr. Gladman has received grants or research support from, or has consulted for, Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Bristol-Myers Squibb, Galapagos, and Gilead.
SEOUL, SOUTH KOREA – Nearly 8% of people with lupus nephritis who achieve complete remission of disease within 1 year of starting treatment will still go on to develop advanced chronic kidney disease (CKD), according to a presentation at an international congress on systemic lupus erythematosus.
Rheumatologist Dafna Gladman, MD, professor of medicine at the University of Toronto and codirector of the Lupus Clinic at Toronto Western Hospital, showed data from the Lupus Clinic’s prospective longitudinal cohort study in 273 patients with confirmed lupus nephritis who achieved complete remission within 12 months of baseline.
Remission was defined as less than 0.5 g proteinuria over 24 hours, inactive urinary sediment, and serum creatinine less than 120% of baseline.
Of this group, 21 (7.7%) progressed to advanced CKD during follow-up, which ranged from 0.7 to 31.7 years with a median of 5.8 years, after enrollment.
Patients who had experienced at least one flare during their first 5 years were around 4.5 times more likely to progress to advanced CKD than were those who did not experience a flare.
While the study excluded patients who already had advanced CKD, the analysis found those with evidence of impaired kidney function at baseline also had more than a fourfold higher risk of developing advanced CKD.
Other significant risk factors for progression were having low complement C3 levels at baseline and having had a longer duration of disease before enrollment.
“Those patients already have abnormal renal function, so the message is that patients who are already in trouble, you’ve got to watch them very carefully,” Dr. Gladman said in an interview.
The study also looked at whether there was a difference between patients who developed advanced CKD earlier – before the median of 5.8 years – or later. While the numbers were small, Dr. Gladman said patients who progressed earlier tended to be older and were more likely to be on antihypertensive treatment and have lower estimated glomerular filtration rate and a lower Systemic Lupus Erythematosus Disease Activity Index–2K, compared with those who progressed later. Some patients also were noncompliant and/or experienced concomitant infections; four had moderate to severe interstitial fibrosis and tubular atrophy.
“We conclude that such patients should be monitored closely despite early remission, and we also highlight the importance of maintenance therapy, which should be communicated to the patients to prevent noncompliance and subsequent flare,” Dr. Gladman told the conference.
Dr. Gladman said her clinic told patients from the very beginning of their treatment that they would need to be seen at 2- to 6-month intervals, regardless of how well their disease was doing.
Commenting on the presentation, rheumatologist Mandana Nikpour MD, PhD, of St. Vincent’s Hospital in Melbourne, said the findings showed the importance of keeping a close eye on patients with lupus nephritis, even if their disease appears to be in remission.
“If you’ve had nephritis, and you go into remission, you may already have a degree of damage in your kidneys,” said Dr. Nikpour, also from the University of Melbourne. “If there’s a degree of uncontrolled hypertension, or if a patient is noncompliant with their treatment, and there’s a degree of grumbling disease activity, that can all conspire and add up to result in long-term kidney damage and loss of renal function.”
Dr. Gladman has received grants or research support from, or has consulted for, Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Bristol-Myers Squibb, Galapagos, and Gilead.
SEOUL, SOUTH KOREA – Nearly 8% of people with lupus nephritis who achieve complete remission of disease within 1 year of starting treatment will still go on to develop advanced chronic kidney disease (CKD), according to a presentation at an international congress on systemic lupus erythematosus.
Rheumatologist Dafna Gladman, MD, professor of medicine at the University of Toronto and codirector of the Lupus Clinic at Toronto Western Hospital, showed data from the Lupus Clinic’s prospective longitudinal cohort study in 273 patients with confirmed lupus nephritis who achieved complete remission within 12 months of baseline.
Remission was defined as less than 0.5 g proteinuria over 24 hours, inactive urinary sediment, and serum creatinine less than 120% of baseline.
Of this group, 21 (7.7%) progressed to advanced CKD during follow-up, which ranged from 0.7 to 31.7 years with a median of 5.8 years, after enrollment.
Patients who had experienced at least one flare during their first 5 years were around 4.5 times more likely to progress to advanced CKD than were those who did not experience a flare.
While the study excluded patients who already had advanced CKD, the analysis found those with evidence of impaired kidney function at baseline also had more than a fourfold higher risk of developing advanced CKD.
Other significant risk factors for progression were having low complement C3 levels at baseline and having had a longer duration of disease before enrollment.
“Those patients already have abnormal renal function, so the message is that patients who are already in trouble, you’ve got to watch them very carefully,” Dr. Gladman said in an interview.
The study also looked at whether there was a difference between patients who developed advanced CKD earlier – before the median of 5.8 years – or later. While the numbers were small, Dr. Gladman said patients who progressed earlier tended to be older and were more likely to be on antihypertensive treatment and have lower estimated glomerular filtration rate and a lower Systemic Lupus Erythematosus Disease Activity Index–2K, compared with those who progressed later. Some patients also were noncompliant and/or experienced concomitant infections; four had moderate to severe interstitial fibrosis and tubular atrophy.
“We conclude that such patients should be monitored closely despite early remission, and we also highlight the importance of maintenance therapy, which should be communicated to the patients to prevent noncompliance and subsequent flare,” Dr. Gladman told the conference.
Dr. Gladman said her clinic told patients from the very beginning of their treatment that they would need to be seen at 2- to 6-month intervals, regardless of how well their disease was doing.
Commenting on the presentation, rheumatologist Mandana Nikpour MD, PhD, of St. Vincent’s Hospital in Melbourne, said the findings showed the importance of keeping a close eye on patients with lupus nephritis, even if their disease appears to be in remission.
“If you’ve had nephritis, and you go into remission, you may already have a degree of damage in your kidneys,” said Dr. Nikpour, also from the University of Melbourne. “If there’s a degree of uncontrolled hypertension, or if a patient is noncompliant with their treatment, and there’s a degree of grumbling disease activity, that can all conspire and add up to result in long-term kidney damage and loss of renal function.”
Dr. Gladman has received grants or research support from, or has consulted for, Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Bristol-Myers Squibb, Galapagos, and Gilead.
AT LUPUS 2023
Coronary artery calcium score bests polygenic risk score in CHD prediction
As a predictor of coronary heart disease (CHD) events, the coronary artery calcium (CAC) score on computed tomography had better risk discrimination than the polygenic risk score, a binational study found. And when added to classic cardiovascular risk factors, the CAC score significantly improved risk classification while the polygenic risk factor score did not.
These findings emerged from two large cohorts of middle-aged and older White adults from the United States and the Netherlands in the first head-to-head comparison of these two approaches. Led by Sadiya S. Kahn, MD, MSc, an assistant professor of medicine (cardiology) and preventive medicine (epidemiology) at Northwestern University, Chicago, the study was published online in JAMA.
There has been much interest in using both genetic factors and CT imaging to better identify individuals at risk for heart disease. “Each approach has advantages and disadvantages, and we wanted to better understand the comparative predictive utility to provide support for what the preferred approach should be,” Dr. Kahn said in an interview. “We focused on middle-aged to older adults for whom current risk prediction equations are relevant in estimating risk with the Pooled Cohort Equation, or PCE.”
The superiority of the CT-imaged coronary artery risk score may be because of its direct visualization of calcification in the arteries and the subclinical disease burden rather than a focus on common genetic variants, Dr. Kahn explained. “In addition, prior studies have demonstrated that genetics, or inherited risk, is not destiny, so this score may not perform as well for risk discrimination as the traditional risk factors themselves along with CT.”
The study
Study participants came from the U.S. Multi-Ethnic Study of Atherosclerosis (MESA, n = 1,991) and the Dutch Rotterdam Study (RS, n = 1,217). Ages ranged from 45 to 79, with the medians in the two cohorts 61 and 68 years, respectively. Slightly more than half of participants in both groups were female.
Traditional risk factors were used to calculate CHD risk with pooled cohort equations, while computed tomography was used to determine the CAC score and genotyped samples for a validated polygenic risk score.
Both scores were significantly associated with 10-year risk of incident CHD.
The median predicted atherosclerotic disease risk based on traditional risk factors was 6.99% in MESA and 5.93% in RS. During the total available follow-up in MESA (median, 16.0 years) and RS (median, 14.2 years), incident CHD occurred in 187 participants (9.4%) and 98 participants (8.1%), respectively.
C (concordance) statistics for the two scores showed the superiority of the CAC. This statistic measures a model’s ability to rank patients from high to low risk, with a value of 1 being perfect risk fit or concordance and 0.70 or more indicating good concordance and risk discrimination. The CAC score had a C statistic of 0.76 (95% confidence interval, 0.71-0.79) vs. 0.69 for the polygenic risk score (95% CI, 0.63-0.71).
When each score was added to PCEs, the C statistics changed as follows: CAC score, 0.09 (95% CI, 0.06-0.13); polygenic risk score, 0.02 (95% CI, 0.00-0.04); and 0.10 (95% CI, 0.07-0.14) for both.
Net reclassification significantly improved with the CAC plus PCEs by the following values: 0.19 (95% CI, 0.06-0.28). The change was not significant, however, with the polygenic risk score plus PCEs: 0.04 (95% CI, –0.05-0.10).
In the clinical setting, Dr. Kahn said, “The use of CT in patients who are at intermediate risk for heart disease can be helpful in refining risk estimation and guiding recommendations for lipid-lowering therapy. Polygenic risk scores are not helpful in middle-aged to older adults above and beyond traditional risk factors for predicting risk of heart disease.”
This study was supported by the National Heart, Lung, and Blood Institute. MESA is supported by the NHLBI. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. Dr. Khan reported grants from the NHLBI and the NIH during the study and outside of the submitted work. Several coauthors reported grant support from, variously, the NIH, the NHLBI, and the American Heart Association.
As a predictor of coronary heart disease (CHD) events, the coronary artery calcium (CAC) score on computed tomography had better risk discrimination than the polygenic risk score, a binational study found. And when added to classic cardiovascular risk factors, the CAC score significantly improved risk classification while the polygenic risk factor score did not.
These findings emerged from two large cohorts of middle-aged and older White adults from the United States and the Netherlands in the first head-to-head comparison of these two approaches. Led by Sadiya S. Kahn, MD, MSc, an assistant professor of medicine (cardiology) and preventive medicine (epidemiology) at Northwestern University, Chicago, the study was published online in JAMA.
There has been much interest in using both genetic factors and CT imaging to better identify individuals at risk for heart disease. “Each approach has advantages and disadvantages, and we wanted to better understand the comparative predictive utility to provide support for what the preferred approach should be,” Dr. Kahn said in an interview. “We focused on middle-aged to older adults for whom current risk prediction equations are relevant in estimating risk with the Pooled Cohort Equation, or PCE.”
The superiority of the CT-imaged coronary artery risk score may be because of its direct visualization of calcification in the arteries and the subclinical disease burden rather than a focus on common genetic variants, Dr. Kahn explained. “In addition, prior studies have demonstrated that genetics, or inherited risk, is not destiny, so this score may not perform as well for risk discrimination as the traditional risk factors themselves along with CT.”
The study
Study participants came from the U.S. Multi-Ethnic Study of Atherosclerosis (MESA, n = 1,991) and the Dutch Rotterdam Study (RS, n = 1,217). Ages ranged from 45 to 79, with the medians in the two cohorts 61 and 68 years, respectively. Slightly more than half of participants in both groups were female.
Traditional risk factors were used to calculate CHD risk with pooled cohort equations, while computed tomography was used to determine the CAC score and genotyped samples for a validated polygenic risk score.
Both scores were significantly associated with 10-year risk of incident CHD.
The median predicted atherosclerotic disease risk based on traditional risk factors was 6.99% in MESA and 5.93% in RS. During the total available follow-up in MESA (median, 16.0 years) and RS (median, 14.2 years), incident CHD occurred in 187 participants (9.4%) and 98 participants (8.1%), respectively.
C (concordance) statistics for the two scores showed the superiority of the CAC. This statistic measures a model’s ability to rank patients from high to low risk, with a value of 1 being perfect risk fit or concordance and 0.70 or more indicating good concordance and risk discrimination. The CAC score had a C statistic of 0.76 (95% confidence interval, 0.71-0.79) vs. 0.69 for the polygenic risk score (95% CI, 0.63-0.71).
When each score was added to PCEs, the C statistics changed as follows: CAC score, 0.09 (95% CI, 0.06-0.13); polygenic risk score, 0.02 (95% CI, 0.00-0.04); and 0.10 (95% CI, 0.07-0.14) for both.
Net reclassification significantly improved with the CAC plus PCEs by the following values: 0.19 (95% CI, 0.06-0.28). The change was not significant, however, with the polygenic risk score plus PCEs: 0.04 (95% CI, –0.05-0.10).
In the clinical setting, Dr. Kahn said, “The use of CT in patients who are at intermediate risk for heart disease can be helpful in refining risk estimation and guiding recommendations for lipid-lowering therapy. Polygenic risk scores are not helpful in middle-aged to older adults above and beyond traditional risk factors for predicting risk of heart disease.”
This study was supported by the National Heart, Lung, and Blood Institute. MESA is supported by the NHLBI. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. Dr. Khan reported grants from the NHLBI and the NIH during the study and outside of the submitted work. Several coauthors reported grant support from, variously, the NIH, the NHLBI, and the American Heart Association.
As a predictor of coronary heart disease (CHD) events, the coronary artery calcium (CAC) score on computed tomography had better risk discrimination than the polygenic risk score, a binational study found. And when added to classic cardiovascular risk factors, the CAC score significantly improved risk classification while the polygenic risk factor score did not.
These findings emerged from two large cohorts of middle-aged and older White adults from the United States and the Netherlands in the first head-to-head comparison of these two approaches. Led by Sadiya S. Kahn, MD, MSc, an assistant professor of medicine (cardiology) and preventive medicine (epidemiology) at Northwestern University, Chicago, the study was published online in JAMA.
There has been much interest in using both genetic factors and CT imaging to better identify individuals at risk for heart disease. “Each approach has advantages and disadvantages, and we wanted to better understand the comparative predictive utility to provide support for what the preferred approach should be,” Dr. Kahn said in an interview. “We focused on middle-aged to older adults for whom current risk prediction equations are relevant in estimating risk with the Pooled Cohort Equation, or PCE.”
The superiority of the CT-imaged coronary artery risk score may be because of its direct visualization of calcification in the arteries and the subclinical disease burden rather than a focus on common genetic variants, Dr. Kahn explained. “In addition, prior studies have demonstrated that genetics, or inherited risk, is not destiny, so this score may not perform as well for risk discrimination as the traditional risk factors themselves along with CT.”
The study
Study participants came from the U.S. Multi-Ethnic Study of Atherosclerosis (MESA, n = 1,991) and the Dutch Rotterdam Study (RS, n = 1,217). Ages ranged from 45 to 79, with the medians in the two cohorts 61 and 68 years, respectively. Slightly more than half of participants in both groups were female.
Traditional risk factors were used to calculate CHD risk with pooled cohort equations, while computed tomography was used to determine the CAC score and genotyped samples for a validated polygenic risk score.
Both scores were significantly associated with 10-year risk of incident CHD.
The median predicted atherosclerotic disease risk based on traditional risk factors was 6.99% in MESA and 5.93% in RS. During the total available follow-up in MESA (median, 16.0 years) and RS (median, 14.2 years), incident CHD occurred in 187 participants (9.4%) and 98 participants (8.1%), respectively.
C (concordance) statistics for the two scores showed the superiority of the CAC. This statistic measures a model’s ability to rank patients from high to low risk, with a value of 1 being perfect risk fit or concordance and 0.70 or more indicating good concordance and risk discrimination. The CAC score had a C statistic of 0.76 (95% confidence interval, 0.71-0.79) vs. 0.69 for the polygenic risk score (95% CI, 0.63-0.71).
When each score was added to PCEs, the C statistics changed as follows: CAC score, 0.09 (95% CI, 0.06-0.13); polygenic risk score, 0.02 (95% CI, 0.00-0.04); and 0.10 (95% CI, 0.07-0.14) for both.
Net reclassification significantly improved with the CAC plus PCEs by the following values: 0.19 (95% CI, 0.06-0.28). The change was not significant, however, with the polygenic risk score plus PCEs: 0.04 (95% CI, –0.05-0.10).
In the clinical setting, Dr. Kahn said, “The use of CT in patients who are at intermediate risk for heart disease can be helpful in refining risk estimation and guiding recommendations for lipid-lowering therapy. Polygenic risk scores are not helpful in middle-aged to older adults above and beyond traditional risk factors for predicting risk of heart disease.”
This study was supported by the National Heart, Lung, and Blood Institute. MESA is supported by the NHLBI. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. Dr. Khan reported grants from the NHLBI and the NIH during the study and outside of the submitted work. Several coauthors reported grant support from, variously, the NIH, the NHLBI, and the American Heart Association.
FROM JAMA
Focus of new ASH VTE guidelines: Thrombophilia testing
according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.
“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.
Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.
The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.
Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.
“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.
The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.
However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:
- Patients with VTE associated with nonsurgical major transient or hormonal risk factors
- Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
- Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
- Pregnant women with a family history of high-risk thrombophilia types
- Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE
“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.
The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.
“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.
Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.
“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.
Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.
The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.
according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.
“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.
Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.
The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.
Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.
“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.
The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.
However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:
- Patients with VTE associated with nonsurgical major transient or hormonal risk factors
- Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
- Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
- Pregnant women with a family history of high-risk thrombophilia types
- Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE
“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.
The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.
“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.
Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.
“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.
Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.
The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.
according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.
“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.
Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.
The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.
Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.
“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.
The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.
However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:
- Patients with VTE associated with nonsurgical major transient or hormonal risk factors
- Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
- Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
- Pregnant women with a family history of high-risk thrombophilia types
- Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE
“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.
The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.
“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.
Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.
“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.
Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.
The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.
FROM BLOOD ADVANCES
What was the impact of COVID-19 on maternal mortality in the United States?
Thoma ME, Declercq ER. Changes in pregnancy-related mortality associated with the coronavirus disease 2019 (COVID-19) pandemic in the United States. Obstet Gynecol. 2023. doi:10.1097/AOG0000000000005182.
EXPERT COMMENTARY
Maternal mortality rates in the United States were embarrassingly high and rising compared with other high-income countries prior to the onset of the COVID-19 pandemic. Recently, Thoma and Declercq aimed to assess the impact of COVID-19 on pregnancy-related deaths within 42 days of childbirth as well as out to 12 months postpartum.1
During the pandemic, many issues may have affected maternity care and birthing experiences, including changes in prenatal care, restrictions that prevented support people from attending labor, and staffing shortages related to hospital overcrowding with personnel assignments away from labor and delivery. The study by Thoma and Declercq looked at maternal mortality from prior to the onset of the pandemic through changes in the health care environment, availability of vaccines, and emergence of more highly contagious and potentially more lethal viral variants.1 All data were stratified by race, ethnicity, and locale. Death rates were compared between urban, metropolitan regions; suburban, mid-size regions; and rural locations.
Details of the study
Data were collected from the Centers for Disease Control and Prevention’s (CDC) publicly available WONDER database from 2019 to 2021. Because the absolute number of deaths within the American Indian/Alaska Native community was relatively small during that timeframe, data from 2018 also were accessed in order to verify reliability. The authors used the CDC’s definition of pregnancy-related death as “a death while pregnant or within 1 year of the end of pregnancy from any cause related to or aggravated by the pregnancy.”2 International Classification of Diseases, Tenth Revision (ICD-10) codes were used to identify maternal deaths. The multiple causes of death file was queried to match maternal deaths with COVID-19 as a contributory cause.
Patterns of maternal deaths were compared with overall COVID-19 cases and COVID-19 death rates for reproductive-age women (ages 15 to 44) by quarters beginning in quarter 1 of 2019. Quarters through the first quarter of 2020 were prepandemic, then quarterly statistics were analyzed from the second quarter of 2020 through the end of 2021 to assess the impact of COVID-19 on early and late maternal mortality.
Findings. Overall maternal mortality rose by 26% from the beginning of 2020 to the second quarter, remained stable through mid-2021, then increased dramatically in the second half of 2021. Maternal mortality unrelated to COVID-19 remained fairly consistent at prior levels, whereas the COVID-19 associateddeaths mirrored the pattern of mortality among reproductive-age nonpregnant women attributed to COVID-19. In addition, the disparities in health outcomes observed in the population at large related to COVID-19 were similar among pregnant people.
American Indian/Alaska Native populations had the largest increase in mortality—more than doubling between early 2020 and the end of 2021. Black people experienced the largest absolute increase in mortality (up to 97.7/100,000 births) while Hispanic birthing people had the highest relative increase (from 19.3 to 29.8/100,000 births). While there were increases in maternal mortality among White and Asian birthing people, these variances were much smaller than for Black, Hispanic, and American Indian/Alaska Native populations.
When comparing mortality stratified by residence areas, early pandemic deaths were higher among birthing people in large urban areas (a 33% increase in 2020); however, later in the pandemic the rates increased substantially in medium-small metropolitan areas (39%) and rural areas (21%).
Study strengths and limitations
The administrative data used to inform this study is a relatively reliable dataset, although errors in both coding for COVID-19 as a contributory cause of maternal death and appropriate ascertainment of race and ethnicity may have occurred. Administrative data can highlight the trends in maternal mortality but cannot identify the root causes of these deaths. We are left with many questions regarding the contribution of staffing, support in labor, changes in prenatal care, and instability in food, housing, and comorbid medical conditions to this devastating rise in maternal mortality. ●
The COVID-19 pandemic resulted in increased maternal mortality overall but in disproportionate increases in maternal mortality in American Indian/Alaska Native, Black, and Hispanic birthing people. The sharpest rise in mortality occurred with the onset of the Delta variant—and after several COVID-19 vaccines were available, which were not tested in or recommended early in 2021 for pregnant people. Vulnerable populations were at highest risk for death associated with COVID-19 during pregnancy. Perhaps this can inform responses to future pandemics and prompt inclusion of pregnant people early in the development of vaccines and prevention strategies.
BARBARA LEVY, MD
- Thoma ME, Declercq ER. Changes in pregnancy-related mortality associated with the coronavirus disease 2019 (COVID-19) pandemic in the United States. Obstet Gynecol. 2023. doi:10.1097/AOG0000000000005182.
- Centers for Disease Control and Prevention. Pregnancy mortality surveillance system. Accessed April 17, 2023. https://www.cdc.gov/reproductivehealth/maternal -mortality/pregnancy-mortality-surveillance-system.htm
Thoma ME, Declercq ER. Changes in pregnancy-related mortality associated with the coronavirus disease 2019 (COVID-19) pandemic in the United States. Obstet Gynecol. 2023. doi:10.1097/AOG0000000000005182.
EXPERT COMMENTARY
Maternal mortality rates in the United States were embarrassingly high and rising compared with other high-income countries prior to the onset of the COVID-19 pandemic. Recently, Thoma and Declercq aimed to assess the impact of COVID-19 on pregnancy-related deaths within 42 days of childbirth as well as out to 12 months postpartum.1
During the pandemic, many issues may have affected maternity care and birthing experiences, including changes in prenatal care, restrictions that prevented support people from attending labor, and staffing shortages related to hospital overcrowding with personnel assignments away from labor and delivery. The study by Thoma and Declercq looked at maternal mortality from prior to the onset of the pandemic through changes in the health care environment, availability of vaccines, and emergence of more highly contagious and potentially more lethal viral variants.1 All data were stratified by race, ethnicity, and locale. Death rates were compared between urban, metropolitan regions; suburban, mid-size regions; and rural locations.
Details of the study
Data were collected from the Centers for Disease Control and Prevention’s (CDC) publicly available WONDER database from 2019 to 2021. Because the absolute number of deaths within the American Indian/Alaska Native community was relatively small during that timeframe, data from 2018 also were accessed in order to verify reliability. The authors used the CDC’s definition of pregnancy-related death as “a death while pregnant or within 1 year of the end of pregnancy from any cause related to or aggravated by the pregnancy.”2 International Classification of Diseases, Tenth Revision (ICD-10) codes were used to identify maternal deaths. The multiple causes of death file was queried to match maternal deaths with COVID-19 as a contributory cause.
Patterns of maternal deaths were compared with overall COVID-19 cases and COVID-19 death rates for reproductive-age women (ages 15 to 44) by quarters beginning in quarter 1 of 2019. Quarters through the first quarter of 2020 were prepandemic, then quarterly statistics were analyzed from the second quarter of 2020 through the end of 2021 to assess the impact of COVID-19 on early and late maternal mortality.
Findings. Overall maternal mortality rose by 26% from the beginning of 2020 to the second quarter, remained stable through mid-2021, then increased dramatically in the second half of 2021. Maternal mortality unrelated to COVID-19 remained fairly consistent at prior levels, whereas the COVID-19 associateddeaths mirrored the pattern of mortality among reproductive-age nonpregnant women attributed to COVID-19. In addition, the disparities in health outcomes observed in the population at large related to COVID-19 were similar among pregnant people.
American Indian/Alaska Native populations had the largest increase in mortality—more than doubling between early 2020 and the end of 2021. Black people experienced the largest absolute increase in mortality (up to 97.7/100,000 births) while Hispanic birthing people had the highest relative increase (from 19.3 to 29.8/100,000 births). While there were increases in maternal mortality among White and Asian birthing people, these variances were much smaller than for Black, Hispanic, and American Indian/Alaska Native populations.
When comparing mortality stratified by residence areas, early pandemic deaths were higher among birthing people in large urban areas (a 33% increase in 2020); however, later in the pandemic the rates increased substantially in medium-small metropolitan areas (39%) and rural areas (21%).
Study strengths and limitations
The administrative data used to inform this study is a relatively reliable dataset, although errors in both coding for COVID-19 as a contributory cause of maternal death and appropriate ascertainment of race and ethnicity may have occurred. Administrative data can highlight the trends in maternal mortality but cannot identify the root causes of these deaths. We are left with many questions regarding the contribution of staffing, support in labor, changes in prenatal care, and instability in food, housing, and comorbid medical conditions to this devastating rise in maternal mortality. ●
The COVID-19 pandemic resulted in increased maternal mortality overall but in disproportionate increases in maternal mortality in American Indian/Alaska Native, Black, and Hispanic birthing people. The sharpest rise in mortality occurred with the onset of the Delta variant—and after several COVID-19 vaccines were available, which were not tested in or recommended early in 2021 for pregnant people. Vulnerable populations were at highest risk for death associated with COVID-19 during pregnancy. Perhaps this can inform responses to future pandemics and prompt inclusion of pregnant people early in the development of vaccines and prevention strategies.
BARBARA LEVY, MD
Thoma ME, Declercq ER. Changes in pregnancy-related mortality associated with the coronavirus disease 2019 (COVID-19) pandemic in the United States. Obstet Gynecol. 2023. doi:10.1097/AOG0000000000005182.
EXPERT COMMENTARY
Maternal mortality rates in the United States were embarrassingly high and rising compared with other high-income countries prior to the onset of the COVID-19 pandemic. Recently, Thoma and Declercq aimed to assess the impact of COVID-19 on pregnancy-related deaths within 42 days of childbirth as well as out to 12 months postpartum.1
During the pandemic, many issues may have affected maternity care and birthing experiences, including changes in prenatal care, restrictions that prevented support people from attending labor, and staffing shortages related to hospital overcrowding with personnel assignments away from labor and delivery. The study by Thoma and Declercq looked at maternal mortality from prior to the onset of the pandemic through changes in the health care environment, availability of vaccines, and emergence of more highly contagious and potentially more lethal viral variants.1 All data were stratified by race, ethnicity, and locale. Death rates were compared between urban, metropolitan regions; suburban, mid-size regions; and rural locations.
Details of the study
Data were collected from the Centers for Disease Control and Prevention’s (CDC) publicly available WONDER database from 2019 to 2021. Because the absolute number of deaths within the American Indian/Alaska Native community was relatively small during that timeframe, data from 2018 also were accessed in order to verify reliability. The authors used the CDC’s definition of pregnancy-related death as “a death while pregnant or within 1 year of the end of pregnancy from any cause related to or aggravated by the pregnancy.”2 International Classification of Diseases, Tenth Revision (ICD-10) codes were used to identify maternal deaths. The multiple causes of death file was queried to match maternal deaths with COVID-19 as a contributory cause.
Patterns of maternal deaths were compared with overall COVID-19 cases and COVID-19 death rates for reproductive-age women (ages 15 to 44) by quarters beginning in quarter 1 of 2019. Quarters through the first quarter of 2020 were prepandemic, then quarterly statistics were analyzed from the second quarter of 2020 through the end of 2021 to assess the impact of COVID-19 on early and late maternal mortality.
Findings. Overall maternal mortality rose by 26% from the beginning of 2020 to the second quarter, remained stable through mid-2021, then increased dramatically in the second half of 2021. Maternal mortality unrelated to COVID-19 remained fairly consistent at prior levels, whereas the COVID-19 associateddeaths mirrored the pattern of mortality among reproductive-age nonpregnant women attributed to COVID-19. In addition, the disparities in health outcomes observed in the population at large related to COVID-19 were similar among pregnant people.
American Indian/Alaska Native populations had the largest increase in mortality—more than doubling between early 2020 and the end of 2021. Black people experienced the largest absolute increase in mortality (up to 97.7/100,000 births) while Hispanic birthing people had the highest relative increase (from 19.3 to 29.8/100,000 births). While there were increases in maternal mortality among White and Asian birthing people, these variances were much smaller than for Black, Hispanic, and American Indian/Alaska Native populations.
When comparing mortality stratified by residence areas, early pandemic deaths were higher among birthing people in large urban areas (a 33% increase in 2020); however, later in the pandemic the rates increased substantially in medium-small metropolitan areas (39%) and rural areas (21%).
Study strengths and limitations
The administrative data used to inform this study is a relatively reliable dataset, although errors in both coding for COVID-19 as a contributory cause of maternal death and appropriate ascertainment of race and ethnicity may have occurred. Administrative data can highlight the trends in maternal mortality but cannot identify the root causes of these deaths. We are left with many questions regarding the contribution of staffing, support in labor, changes in prenatal care, and instability in food, housing, and comorbid medical conditions to this devastating rise in maternal mortality. ●
The COVID-19 pandemic resulted in increased maternal mortality overall but in disproportionate increases in maternal mortality in American Indian/Alaska Native, Black, and Hispanic birthing people. The sharpest rise in mortality occurred with the onset of the Delta variant—and after several COVID-19 vaccines were available, which were not tested in or recommended early in 2021 for pregnant people. Vulnerable populations were at highest risk for death associated with COVID-19 during pregnancy. Perhaps this can inform responses to future pandemics and prompt inclusion of pregnant people early in the development of vaccines and prevention strategies.
BARBARA LEVY, MD
- Thoma ME, Declercq ER. Changes in pregnancy-related mortality associated with the coronavirus disease 2019 (COVID-19) pandemic in the United States. Obstet Gynecol. 2023. doi:10.1097/AOG0000000000005182.
- Centers for Disease Control and Prevention. Pregnancy mortality surveillance system. Accessed April 17, 2023. https://www.cdc.gov/reproductivehealth/maternal -mortality/pregnancy-mortality-surveillance-system.htm
- Thoma ME, Declercq ER. Changes in pregnancy-related mortality associated with the coronavirus disease 2019 (COVID-19) pandemic in the United States. Obstet Gynecol. 2023. doi:10.1097/AOG0000000000005182.
- Centers for Disease Control and Prevention. Pregnancy mortality surveillance system. Accessed April 17, 2023. https://www.cdc.gov/reproductivehealth/maternal -mortality/pregnancy-mortality-surveillance-system.htm
CKD Screening in all U.S. adults found cost effective
(UACR) followed by confirmatory tests and treatment of confirmed cases with current standard-care medications, according to an analysis published in the Annals of Internal Medicine.
This new evidence may prove important as the U.S. Preventive Services Task Force has begun revisiting its 2012 conclusion that “evidence is insufficient to assess the balance of benefits and harms of routine screening for chronic kidney disease in asymptomatic adults.”
A big difference between 2012 and today has been that sodium-glucose cotransporter 2 (SGLT2) inhibitors arrived on the scene as an important complement to well-established treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. SGLT2 inhibitors have been documented as safe and effective for slowing CKD progression regardless of a person’s diabetes status, and have “dramatically altered” first-line treatment of adults with CKD, wrote the authors of the new study.
‘Large population health gains’ from CKD screening
“Given the high prevalence of CKD, even among those without risk factors, low-cost screening combined with effective treatment using SGLT2 inhibitors represent value,” explained Marika M. Cusick, lead author of the report, a PhD student, and a health policy researcher at Stanford (Calif.) University. “Our results show large population health gains can be achieved through CKD screening,” she said in an interview.
“This is a well-designed cost-effectiveness analysis that, importantly, considers newer treatments shown to be effective for slowing progression of CKD. The overall findings are convincing,” commented Deidra C. Crews, MD, a nephrologist and professor at Johns Hopkins University in Baltimore who was not involved in the research.
Dr. Crews, who is also president-elect of the American Society of Nephrology noted that the findings “may be a conservative estimate of the cost-effectiveness of CKD screening in certain subgroups, particularly when considering profound racial, ethnic and socioeconomic disparities in survival and CKD progression.”
The USPSTF starts a relook
The new evidence of cost-effectiveness of routine CKD screening follows the USPSTF’s release in January 2023 of a draft research plan to reassess the potential role for CKD screening of asymptomatic adults in the United States, the first step on a potential path to a revised set of recommendations. Public comment on the draft plan closed in February, and based on the standard USPSTF development steps and time frames, a final recommendation statement could appear by early 2026.
Revisiting the prior USPSTF decision from 2012 received endorsement earlier in 2023 from the ASN. The organization issued a statement last January that cited “more than a decade of advocacy in support of more kidney health screening by ASN and other stakeholders dedicated to intervening earlier to slow or stop the progression of kidney diseases.”
A more detailed letter of support for CKD screening sent to top USPSTF officials followed in February 2023 from ASN president Michelle A. Josephson, MD, who said in part that “ASN believes that kidney care is at an inflection point. There are now far more novel therapeutics to slow the progression of CKD, evidence to support the impact of nonpharmacologic interventions on CKD, and an increased commitment in public health to confront disparities and their causes.”
USPSTF recommendation could make a difference
Dr. Josephson also cited the modest effect that CKD screening recommendations from other groups have had up to now.
“Although guidance from Kidney Disease Improving Global Outcomes and the National Kidney Foundation recommends CKD screening among patients with hypertension, only approximately 10% of individuals with hypertension receive yearly screening. Furthermore, American Diabetes Association guidelines recommend yearly CKD screening in patients with diabetes, but only 40%-50% of patients receive this.”
“USPSTF recommendations tend to reach clinicians in primary care settings, where screening for diseases most commonly occurs, much more than recommendations from professional or patient organizations,” Dr. Crews said in an interview. “USPSTF recommendations also often influence health policies that might financially incentivize clinicians and health systems to screen their patients.”
“We hope [the USPSTF] will be interested in including our results within the totality of evidence assessed in their review of CKD screening,” said Ms. Cusick.
Preventing hundreds of thousands dialysis cases
The Stanford researchers developed a decision analytic Markov cohort model of CKD progression in U.S. adults aged 35 years or older and fit their model to data from the National Health and Nutrition Examination Survey (NHANES). They found that implementing one-time screening and adding SGLT2 inhibitors to treatment of the 158 million U.S. adults 35-75 years old would prevent the need for kidney replacement therapy (dialysis or transplant) in approximately 398,000 people over their lifetimes, representing a 10% decrease in such cases, compared with the status quo. Screening every 10 or 5 years combined with SGLT2 inhibitors would prevent approximately 598,000 or 658,000 people, respectively, from requiring kidney replacement therapy, compared with not screening.
Analysis showed that one-time screening produced an incremental cost-effectiveness ratio of $86,300 per quality-adjusted life-year (QALY) gained when one-time screening occurred in adults when they reached 55 years old. Screening every 10 years until people became 75 years old cost $98,400 per QALY gained for this group when adults were 35 years old, and $89,800 per QALY gained when screening occurred at 65 years old. These QALY costs are less than “commonly used” U.S. thresholds for acceptable cost-effectiveness of $100,000-$150,000 per QALY gained, the authors said.
Ms. Cusick highlighted the advantages of population-level screening for all U.S. adults, including those who are asymptomatic, compared with focusing on adults with risk factors, such as hypertension or diabetes.
“While risk-based screening can be more cost effective in some settings, risk factors are not always known, especially in marginalized and disadvantaged populations. This may lead to disparities in the use of screening and downstream health outcomes that could be avoided through universal screening policies,” she explained.
The study received no commercial funding. Ms. Cusick had no disclosures. Dr. Crews has received research grants from Somatus. Dr. Josephson has been a consultant to Exosome Diagnostics, IMMUCOR, Labcorp, Otsuka, UBC, and Vera Therapeutics, and has an ownership interest in Seagen.
(UACR) followed by confirmatory tests and treatment of confirmed cases with current standard-care medications, according to an analysis published in the Annals of Internal Medicine.
This new evidence may prove important as the U.S. Preventive Services Task Force has begun revisiting its 2012 conclusion that “evidence is insufficient to assess the balance of benefits and harms of routine screening for chronic kidney disease in asymptomatic adults.”
A big difference between 2012 and today has been that sodium-glucose cotransporter 2 (SGLT2) inhibitors arrived on the scene as an important complement to well-established treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. SGLT2 inhibitors have been documented as safe and effective for slowing CKD progression regardless of a person’s diabetes status, and have “dramatically altered” first-line treatment of adults with CKD, wrote the authors of the new study.
‘Large population health gains’ from CKD screening
“Given the high prevalence of CKD, even among those without risk factors, low-cost screening combined with effective treatment using SGLT2 inhibitors represent value,” explained Marika M. Cusick, lead author of the report, a PhD student, and a health policy researcher at Stanford (Calif.) University. “Our results show large population health gains can be achieved through CKD screening,” she said in an interview.
“This is a well-designed cost-effectiveness analysis that, importantly, considers newer treatments shown to be effective for slowing progression of CKD. The overall findings are convincing,” commented Deidra C. Crews, MD, a nephrologist and professor at Johns Hopkins University in Baltimore who was not involved in the research.
Dr. Crews, who is also president-elect of the American Society of Nephrology noted that the findings “may be a conservative estimate of the cost-effectiveness of CKD screening in certain subgroups, particularly when considering profound racial, ethnic and socioeconomic disparities in survival and CKD progression.”
The USPSTF starts a relook
The new evidence of cost-effectiveness of routine CKD screening follows the USPSTF’s release in January 2023 of a draft research plan to reassess the potential role for CKD screening of asymptomatic adults in the United States, the first step on a potential path to a revised set of recommendations. Public comment on the draft plan closed in February, and based on the standard USPSTF development steps and time frames, a final recommendation statement could appear by early 2026.
Revisiting the prior USPSTF decision from 2012 received endorsement earlier in 2023 from the ASN. The organization issued a statement last January that cited “more than a decade of advocacy in support of more kidney health screening by ASN and other stakeholders dedicated to intervening earlier to slow or stop the progression of kidney diseases.”
A more detailed letter of support for CKD screening sent to top USPSTF officials followed in February 2023 from ASN president Michelle A. Josephson, MD, who said in part that “ASN believes that kidney care is at an inflection point. There are now far more novel therapeutics to slow the progression of CKD, evidence to support the impact of nonpharmacologic interventions on CKD, and an increased commitment in public health to confront disparities and their causes.”
USPSTF recommendation could make a difference
Dr. Josephson also cited the modest effect that CKD screening recommendations from other groups have had up to now.
“Although guidance from Kidney Disease Improving Global Outcomes and the National Kidney Foundation recommends CKD screening among patients with hypertension, only approximately 10% of individuals with hypertension receive yearly screening. Furthermore, American Diabetes Association guidelines recommend yearly CKD screening in patients with diabetes, but only 40%-50% of patients receive this.”
“USPSTF recommendations tend to reach clinicians in primary care settings, where screening for diseases most commonly occurs, much more than recommendations from professional or patient organizations,” Dr. Crews said in an interview. “USPSTF recommendations also often influence health policies that might financially incentivize clinicians and health systems to screen their patients.”
“We hope [the USPSTF] will be interested in including our results within the totality of evidence assessed in their review of CKD screening,” said Ms. Cusick.
Preventing hundreds of thousands dialysis cases
The Stanford researchers developed a decision analytic Markov cohort model of CKD progression in U.S. adults aged 35 years or older and fit their model to data from the National Health and Nutrition Examination Survey (NHANES). They found that implementing one-time screening and adding SGLT2 inhibitors to treatment of the 158 million U.S. adults 35-75 years old would prevent the need for kidney replacement therapy (dialysis or transplant) in approximately 398,000 people over their lifetimes, representing a 10% decrease in such cases, compared with the status quo. Screening every 10 or 5 years combined with SGLT2 inhibitors would prevent approximately 598,000 or 658,000 people, respectively, from requiring kidney replacement therapy, compared with not screening.
Analysis showed that one-time screening produced an incremental cost-effectiveness ratio of $86,300 per quality-adjusted life-year (QALY) gained when one-time screening occurred in adults when they reached 55 years old. Screening every 10 years until people became 75 years old cost $98,400 per QALY gained for this group when adults were 35 years old, and $89,800 per QALY gained when screening occurred at 65 years old. These QALY costs are less than “commonly used” U.S. thresholds for acceptable cost-effectiveness of $100,000-$150,000 per QALY gained, the authors said.
Ms. Cusick highlighted the advantages of population-level screening for all U.S. adults, including those who are asymptomatic, compared with focusing on adults with risk factors, such as hypertension or diabetes.
“While risk-based screening can be more cost effective in some settings, risk factors are not always known, especially in marginalized and disadvantaged populations. This may lead to disparities in the use of screening and downstream health outcomes that could be avoided through universal screening policies,” she explained.
The study received no commercial funding. Ms. Cusick had no disclosures. Dr. Crews has received research grants from Somatus. Dr. Josephson has been a consultant to Exosome Diagnostics, IMMUCOR, Labcorp, Otsuka, UBC, and Vera Therapeutics, and has an ownership interest in Seagen.
(UACR) followed by confirmatory tests and treatment of confirmed cases with current standard-care medications, according to an analysis published in the Annals of Internal Medicine.
This new evidence may prove important as the U.S. Preventive Services Task Force has begun revisiting its 2012 conclusion that “evidence is insufficient to assess the balance of benefits and harms of routine screening for chronic kidney disease in asymptomatic adults.”
A big difference between 2012 and today has been that sodium-glucose cotransporter 2 (SGLT2) inhibitors arrived on the scene as an important complement to well-established treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. SGLT2 inhibitors have been documented as safe and effective for slowing CKD progression regardless of a person’s diabetes status, and have “dramatically altered” first-line treatment of adults with CKD, wrote the authors of the new study.
‘Large population health gains’ from CKD screening
“Given the high prevalence of CKD, even among those without risk factors, low-cost screening combined with effective treatment using SGLT2 inhibitors represent value,” explained Marika M. Cusick, lead author of the report, a PhD student, and a health policy researcher at Stanford (Calif.) University. “Our results show large population health gains can be achieved through CKD screening,” she said in an interview.
“This is a well-designed cost-effectiveness analysis that, importantly, considers newer treatments shown to be effective for slowing progression of CKD. The overall findings are convincing,” commented Deidra C. Crews, MD, a nephrologist and professor at Johns Hopkins University in Baltimore who was not involved in the research.
Dr. Crews, who is also president-elect of the American Society of Nephrology noted that the findings “may be a conservative estimate of the cost-effectiveness of CKD screening in certain subgroups, particularly when considering profound racial, ethnic and socioeconomic disparities in survival and CKD progression.”
The USPSTF starts a relook
The new evidence of cost-effectiveness of routine CKD screening follows the USPSTF’s release in January 2023 of a draft research plan to reassess the potential role for CKD screening of asymptomatic adults in the United States, the first step on a potential path to a revised set of recommendations. Public comment on the draft plan closed in February, and based on the standard USPSTF development steps and time frames, a final recommendation statement could appear by early 2026.
Revisiting the prior USPSTF decision from 2012 received endorsement earlier in 2023 from the ASN. The organization issued a statement last January that cited “more than a decade of advocacy in support of more kidney health screening by ASN and other stakeholders dedicated to intervening earlier to slow or stop the progression of kidney diseases.”
A more detailed letter of support for CKD screening sent to top USPSTF officials followed in February 2023 from ASN president Michelle A. Josephson, MD, who said in part that “ASN believes that kidney care is at an inflection point. There are now far more novel therapeutics to slow the progression of CKD, evidence to support the impact of nonpharmacologic interventions on CKD, and an increased commitment in public health to confront disparities and their causes.”
USPSTF recommendation could make a difference
Dr. Josephson also cited the modest effect that CKD screening recommendations from other groups have had up to now.
“Although guidance from Kidney Disease Improving Global Outcomes and the National Kidney Foundation recommends CKD screening among patients with hypertension, only approximately 10% of individuals with hypertension receive yearly screening. Furthermore, American Diabetes Association guidelines recommend yearly CKD screening in patients with diabetes, but only 40%-50% of patients receive this.”
“USPSTF recommendations tend to reach clinicians in primary care settings, where screening for diseases most commonly occurs, much more than recommendations from professional or patient organizations,” Dr. Crews said in an interview. “USPSTF recommendations also often influence health policies that might financially incentivize clinicians and health systems to screen their patients.”
“We hope [the USPSTF] will be interested in including our results within the totality of evidence assessed in their review of CKD screening,” said Ms. Cusick.
Preventing hundreds of thousands dialysis cases
The Stanford researchers developed a decision analytic Markov cohort model of CKD progression in U.S. adults aged 35 years or older and fit their model to data from the National Health and Nutrition Examination Survey (NHANES). They found that implementing one-time screening and adding SGLT2 inhibitors to treatment of the 158 million U.S. adults 35-75 years old would prevent the need for kidney replacement therapy (dialysis or transplant) in approximately 398,000 people over their lifetimes, representing a 10% decrease in such cases, compared with the status quo. Screening every 10 or 5 years combined with SGLT2 inhibitors would prevent approximately 598,000 or 658,000 people, respectively, from requiring kidney replacement therapy, compared with not screening.
Analysis showed that one-time screening produced an incremental cost-effectiveness ratio of $86,300 per quality-adjusted life-year (QALY) gained when one-time screening occurred in adults when they reached 55 years old. Screening every 10 years until people became 75 years old cost $98,400 per QALY gained for this group when adults were 35 years old, and $89,800 per QALY gained when screening occurred at 65 years old. These QALY costs are less than “commonly used” U.S. thresholds for acceptable cost-effectiveness of $100,000-$150,000 per QALY gained, the authors said.
Ms. Cusick highlighted the advantages of population-level screening for all U.S. adults, including those who are asymptomatic, compared with focusing on adults with risk factors, such as hypertension or diabetes.
“While risk-based screening can be more cost effective in some settings, risk factors are not always known, especially in marginalized and disadvantaged populations. This may lead to disparities in the use of screening and downstream health outcomes that could be avoided through universal screening policies,” she explained.
The study received no commercial funding. Ms. Cusick had no disclosures. Dr. Crews has received research grants from Somatus. Dr. Josephson has been a consultant to Exosome Diagnostics, IMMUCOR, Labcorp, Otsuka, UBC, and Vera Therapeutics, and has an ownership interest in Seagen.
FROM ANNALS OF INTERNAL MEDICINE
What would you do if ... ?
A few weeks ago we went to Phoenix Theater’s production of “A Chorus Line.” As with all their shows, it was excellent.
The penultimate scene is where one of the auditioning dancers suffers a career-ending injury, forcing the others to consider what they’d do if they couldn’t dance anymore, and facing the fact that sooner or later it will happen to all of them.
Let’s flip it onto us: What if tomorrow you couldn’t practice medicine anymore? To keep it from getting too depressing, let’s say it was because of paperwork. Your medical license expired and you weren’t warned in advance, and because of some legal glitch you can’t ever renew it now.
It’s a good question. I mean, I’ve wanted to be doctor as long as I can remember. (Actually I wanted to be Batman, then a scientist, then a doctor. Though I’d still rather be Batman. I’m even the same age as he was in The Dark Knight Returns.)
For all the paperwork and insurance fights and aggravations the job brings, I still love doing it. I get up on weekday mornings and feel good about going to the office. I generally feel good about what I’ve done to help people (or at least did my best to try) at the end of the day.
During my first year of residency (30 years ago) I remember telling my parents that, if even if I were phenomenally wealthy, I’d still do this job for free. Well, I’m not phenomenally wealthy, but I still enjoy the job.
If I couldn’t do it anymore, I’d be pretty sad. I mean, it’s not like I couldn’t find something else – consulting, research, writing, joining my daughter at her bakery – but I doubt I’d like it as much. Even if money weren’t an issue, there’s only so many jigsaw puzzles to do and books to read.
What about you?
Realistically, most of us won’t do this for the rest of our lives. Our expiration date may be longer than that of a professional dancer, but we still have one. Even if the mind stays sharp, sooner or later we all reach a point where it’s time to move on and leave the field in the capable hands of the next generation, just as a prior group of physicians left it to us. As the line in the song states, “the gift was ours to borrow.” And yes, I still see being able to do this for a living as a privilege and gift. But inevitably we all have to pass it on to the next ones, as will they someday.
But I’ll miss it. An oncologist I know was retired for a few months before he signed up for a nonmedical volunteer job at his old hospital, helping people find the rooms and departments they need to go to. He’s happy with it.
But when you do, you need to do your best to do it without regret. After all, you got to do something that many only dream of. Helping others and (I hope) having a job you enjoy.
I have dancers, and retired dancers, in my practice. The retired ones still miss it, but very few of them leave. They do volunteer teaching at community theaters, or just keep dancing on their own in groups of like-minded friends, as best they can. While medicine has made us one of the longer-lived mammals, it doesn’t stop the years.
When it’s time to walk away and point to tomorrow, do it without regrets, and remember that, even with the sweetness and the sorrow, it was what you did for love.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
A few weeks ago we went to Phoenix Theater’s production of “A Chorus Line.” As with all their shows, it was excellent.
The penultimate scene is where one of the auditioning dancers suffers a career-ending injury, forcing the others to consider what they’d do if they couldn’t dance anymore, and facing the fact that sooner or later it will happen to all of them.
Let’s flip it onto us: What if tomorrow you couldn’t practice medicine anymore? To keep it from getting too depressing, let’s say it was because of paperwork. Your medical license expired and you weren’t warned in advance, and because of some legal glitch you can’t ever renew it now.
It’s a good question. I mean, I’ve wanted to be doctor as long as I can remember. (Actually I wanted to be Batman, then a scientist, then a doctor. Though I’d still rather be Batman. I’m even the same age as he was in The Dark Knight Returns.)
For all the paperwork and insurance fights and aggravations the job brings, I still love doing it. I get up on weekday mornings and feel good about going to the office. I generally feel good about what I’ve done to help people (or at least did my best to try) at the end of the day.
During my first year of residency (30 years ago) I remember telling my parents that, if even if I were phenomenally wealthy, I’d still do this job for free. Well, I’m not phenomenally wealthy, but I still enjoy the job.
If I couldn’t do it anymore, I’d be pretty sad. I mean, it’s not like I couldn’t find something else – consulting, research, writing, joining my daughter at her bakery – but I doubt I’d like it as much. Even if money weren’t an issue, there’s only so many jigsaw puzzles to do and books to read.
What about you?
Realistically, most of us won’t do this for the rest of our lives. Our expiration date may be longer than that of a professional dancer, but we still have one. Even if the mind stays sharp, sooner or later we all reach a point where it’s time to move on and leave the field in the capable hands of the next generation, just as a prior group of physicians left it to us. As the line in the song states, “the gift was ours to borrow.” And yes, I still see being able to do this for a living as a privilege and gift. But inevitably we all have to pass it on to the next ones, as will they someday.
But I’ll miss it. An oncologist I know was retired for a few months before he signed up for a nonmedical volunteer job at his old hospital, helping people find the rooms and departments they need to go to. He’s happy with it.
But when you do, you need to do your best to do it without regret. After all, you got to do something that many only dream of. Helping others and (I hope) having a job you enjoy.
I have dancers, and retired dancers, in my practice. The retired ones still miss it, but very few of them leave. They do volunteer teaching at community theaters, or just keep dancing on their own in groups of like-minded friends, as best they can. While medicine has made us one of the longer-lived mammals, it doesn’t stop the years.
When it’s time to walk away and point to tomorrow, do it without regrets, and remember that, even with the sweetness and the sorrow, it was what you did for love.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
A few weeks ago we went to Phoenix Theater’s production of “A Chorus Line.” As with all their shows, it was excellent.
The penultimate scene is where one of the auditioning dancers suffers a career-ending injury, forcing the others to consider what they’d do if they couldn’t dance anymore, and facing the fact that sooner or later it will happen to all of them.
Let’s flip it onto us: What if tomorrow you couldn’t practice medicine anymore? To keep it from getting too depressing, let’s say it was because of paperwork. Your medical license expired and you weren’t warned in advance, and because of some legal glitch you can’t ever renew it now.
It’s a good question. I mean, I’ve wanted to be doctor as long as I can remember. (Actually I wanted to be Batman, then a scientist, then a doctor. Though I’d still rather be Batman. I’m even the same age as he was in The Dark Knight Returns.)
For all the paperwork and insurance fights and aggravations the job brings, I still love doing it. I get up on weekday mornings and feel good about going to the office. I generally feel good about what I’ve done to help people (or at least did my best to try) at the end of the day.
During my first year of residency (30 years ago) I remember telling my parents that, if even if I were phenomenally wealthy, I’d still do this job for free. Well, I’m not phenomenally wealthy, but I still enjoy the job.
If I couldn’t do it anymore, I’d be pretty sad. I mean, it’s not like I couldn’t find something else – consulting, research, writing, joining my daughter at her bakery – but I doubt I’d like it as much. Even if money weren’t an issue, there’s only so many jigsaw puzzles to do and books to read.
What about you?
Realistically, most of us won’t do this for the rest of our lives. Our expiration date may be longer than that of a professional dancer, but we still have one. Even if the mind stays sharp, sooner or later we all reach a point where it’s time to move on and leave the field in the capable hands of the next generation, just as a prior group of physicians left it to us. As the line in the song states, “the gift was ours to borrow.” And yes, I still see being able to do this for a living as a privilege and gift. But inevitably we all have to pass it on to the next ones, as will they someday.
But I’ll miss it. An oncologist I know was retired for a few months before he signed up for a nonmedical volunteer job at his old hospital, helping people find the rooms and departments they need to go to. He’s happy with it.
But when you do, you need to do your best to do it without regret. After all, you got to do something that many only dream of. Helping others and (I hope) having a job you enjoy.
I have dancers, and retired dancers, in my practice. The retired ones still miss it, but very few of them leave. They do volunteer teaching at community theaters, or just keep dancing on their own in groups of like-minded friends, as best they can. While medicine has made us one of the longer-lived mammals, it doesn’t stop the years.
When it’s time to walk away and point to tomorrow, do it without regrets, and remember that, even with the sweetness and the sorrow, it was what you did for love.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.