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AI in medicine has a major Cassandra problem
This transcript has been edited for clarity.
Today I’m going to talk to you about a study at the cutting edge of modern medicine, one that uses an artificial intelligence (AI) model to guide care. But before I do, I need to take you back to the late Bronze Age, to a city located on the coast of what is now Turkey.
Troy’s towering walls made it seem unassailable, but that would not stop the Achaeans and their fleet of black ships from making landfall, and, after a siege, destroying the city. The destruction of Troy, as told in the Iliad and the Aeneid, was foretold by Cassandra, the daughter of King Priam and Priestess of Troy.
Cassandra had been given the gift of prophecy by the god Apollo in exchange for her favors. But after the gift was bestowed, she rejected the bright god and, in his rage, he added a curse to her blessing: that no one would ever believe her prophecies.
Thus it was that when her brother Paris set off to Sparta to abduct Helen, she warned him that his actions would lead to the downfall of their great city. He, of course, ignored her.
And you know the rest of the story.
Why am I telling you the story of Cassandra of Troy when we’re supposed to be talking about AI in medicine? Because AI has a major Cassandra problem.
The recent history of AI, and particularly the subset of AI known as machine learning in medicine, has been characterized by an accuracy arms race.
The electronic health record allows for the collection of volumes of data orders of magnitude greater than what we have ever been able to collect before. And all that data can be crunched by various algorithms to make predictions about, well, anything – whether a patient will be transferred to the intensive care unit, whether a GI bleed will need an intervention, whether someone will die in the next year.
Studies in this area tend to rely on retrospective datasets, and as time has gone on, better algorithms and more data have led to better and better predictions. In some simpler cases, machine-learning models have achieved near-perfect accuracy – Cassandra-level accuracy – as in the reading of chest x-rays for pneumonia, for example.
But as Cassandra teaches us, even perfect prediction is useless if no one believes you, if they don’t change their behavior. And this is the central problem of AI in medicine today. Many people are focusing on accuracy of the prediction but have forgotten that high accuracy is just table stakes for an AI model to be useful. It has to not only be accurate, but its use also has to change outcomes for patients. We need to be able to save Troy.
The best way to determine whether an AI model will help patients is to treat a model like we treat a new medication and evaluate it through a randomized trial. That’s what researchers, led by Shannon Walker of Vanderbilt University, Nashville, Tenn., did in a paper appearing in JAMA Network Open.
The model in question was one that predicted venous thromboembolism – blood clots – in hospitalized children. The model took in a variety of data points from the health record: a history of blood clot, history of cancer, presence of a central line, a variety of lab values. And the predictive model was very good – maybe not Cassandra good, but it achieved an AUC of 0.90, which means it had very high accuracy.
But again, accuracy is just table stakes.
The authors deployed the model in the live health record and recorded the results. For half of the kids, that was all that happened; no one actually saw the predictions. For those randomized to the intervention, the hematology team would be notified when the risk for clot was calculated to be greater than 2.5%. The hematology team would then contact the primary team to discuss prophylactic anticoagulation.
This is an elegant approach.
Let’s start with those table stakes – accuracy. The predictions were, by and large, pretty accurate in this trial. Of the 135 kids who developed blood clots, 121 had been flagged by the model in advance. That’s about 90%. The model flagged about 10% of kids who didn’t get a blood clot as well, but that’s not entirely surprising since the threshold for flagging was a 2.5% risk.
Given that the model preidentified almost every kid who would go on to develop a blood clot, it would make sense that kids randomized to the intervention would do better; after all, Cassandra was calling out her warnings.
But those kids didn’t do better. The rate of blood clot was no different between the group that used the accurate prediction model and the group that did not.
Why? Why does the use of an accurate model not necessarily improve outcomes?
First of all, a warning must lead to some change in management. Indeed, the kids in the intervention group were more likely to receive anticoagulation, but barely so. There were lots of reasons for this: physician preference, imminent discharge, active bleeding, and so on.
But let’s take a look at the 77 kids in the intervention arm who developed blood clots, because I think this is an instructive analysis.
Six of them did not meet the 2.5% threshold criteria, a case where the model missed its mark. Again, accuracy is table stakes.
Of the remaining 71, only 16 got a recommendation from the hematologist to start anticoagulation. Why not more? Well, the model identified some of the high-risk kids on the weekend, and it seems that the study team did not contact treatment teams during that time. That may account for about 40% of these cases. The remainder had some contraindication to anticoagulation.
Most tellingly, of the 16 who did get a recommendation to start anticoagulation, the recommendation was followed in only seven patients.
This is the gap between accurate prediction and the ability to change outcomes for patients. A prediction is useless if it is wrong, for sure. But it’s also useless if you don’t tell anyone about it. It’s useless if you tell someone but they can’t do anything about it. And it’s useless if they could do something about it but choose not to.
That’s the gulf that these models need to cross at this point. So, the next time some slick company tells you how accurate their AI model is, ask them if accuracy is really the most important thing. If they say, “Well, yes, of course,” then tell them about Cassandra.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Today I’m going to talk to you about a study at the cutting edge of modern medicine, one that uses an artificial intelligence (AI) model to guide care. But before I do, I need to take you back to the late Bronze Age, to a city located on the coast of what is now Turkey.
Troy’s towering walls made it seem unassailable, but that would not stop the Achaeans and their fleet of black ships from making landfall, and, after a siege, destroying the city. The destruction of Troy, as told in the Iliad and the Aeneid, was foretold by Cassandra, the daughter of King Priam and Priestess of Troy.
Cassandra had been given the gift of prophecy by the god Apollo in exchange for her favors. But after the gift was bestowed, she rejected the bright god and, in his rage, he added a curse to her blessing: that no one would ever believe her prophecies.
Thus it was that when her brother Paris set off to Sparta to abduct Helen, she warned him that his actions would lead to the downfall of their great city. He, of course, ignored her.
And you know the rest of the story.
Why am I telling you the story of Cassandra of Troy when we’re supposed to be talking about AI in medicine? Because AI has a major Cassandra problem.
The recent history of AI, and particularly the subset of AI known as machine learning in medicine, has been characterized by an accuracy arms race.
The electronic health record allows for the collection of volumes of data orders of magnitude greater than what we have ever been able to collect before. And all that data can be crunched by various algorithms to make predictions about, well, anything – whether a patient will be transferred to the intensive care unit, whether a GI bleed will need an intervention, whether someone will die in the next year.
Studies in this area tend to rely on retrospective datasets, and as time has gone on, better algorithms and more data have led to better and better predictions. In some simpler cases, machine-learning models have achieved near-perfect accuracy – Cassandra-level accuracy – as in the reading of chest x-rays for pneumonia, for example.
But as Cassandra teaches us, even perfect prediction is useless if no one believes you, if they don’t change their behavior. And this is the central problem of AI in medicine today. Many people are focusing on accuracy of the prediction but have forgotten that high accuracy is just table stakes for an AI model to be useful. It has to not only be accurate, but its use also has to change outcomes for patients. We need to be able to save Troy.
The best way to determine whether an AI model will help patients is to treat a model like we treat a new medication and evaluate it through a randomized trial. That’s what researchers, led by Shannon Walker of Vanderbilt University, Nashville, Tenn., did in a paper appearing in JAMA Network Open.
The model in question was one that predicted venous thromboembolism – blood clots – in hospitalized children. The model took in a variety of data points from the health record: a history of blood clot, history of cancer, presence of a central line, a variety of lab values. And the predictive model was very good – maybe not Cassandra good, but it achieved an AUC of 0.90, which means it had very high accuracy.
But again, accuracy is just table stakes.
The authors deployed the model in the live health record and recorded the results. For half of the kids, that was all that happened; no one actually saw the predictions. For those randomized to the intervention, the hematology team would be notified when the risk for clot was calculated to be greater than 2.5%. The hematology team would then contact the primary team to discuss prophylactic anticoagulation.
This is an elegant approach.
Let’s start with those table stakes – accuracy. The predictions were, by and large, pretty accurate in this trial. Of the 135 kids who developed blood clots, 121 had been flagged by the model in advance. That’s about 90%. The model flagged about 10% of kids who didn’t get a blood clot as well, but that’s not entirely surprising since the threshold for flagging was a 2.5% risk.
Given that the model preidentified almost every kid who would go on to develop a blood clot, it would make sense that kids randomized to the intervention would do better; after all, Cassandra was calling out her warnings.
But those kids didn’t do better. The rate of blood clot was no different between the group that used the accurate prediction model and the group that did not.
Why? Why does the use of an accurate model not necessarily improve outcomes?
First of all, a warning must lead to some change in management. Indeed, the kids in the intervention group were more likely to receive anticoagulation, but barely so. There were lots of reasons for this: physician preference, imminent discharge, active bleeding, and so on.
But let’s take a look at the 77 kids in the intervention arm who developed blood clots, because I think this is an instructive analysis.
Six of them did not meet the 2.5% threshold criteria, a case where the model missed its mark. Again, accuracy is table stakes.
Of the remaining 71, only 16 got a recommendation from the hematologist to start anticoagulation. Why not more? Well, the model identified some of the high-risk kids on the weekend, and it seems that the study team did not contact treatment teams during that time. That may account for about 40% of these cases. The remainder had some contraindication to anticoagulation.
Most tellingly, of the 16 who did get a recommendation to start anticoagulation, the recommendation was followed in only seven patients.
This is the gap between accurate prediction and the ability to change outcomes for patients. A prediction is useless if it is wrong, for sure. But it’s also useless if you don’t tell anyone about it. It’s useless if you tell someone but they can’t do anything about it. And it’s useless if they could do something about it but choose not to.
That’s the gulf that these models need to cross at this point. So, the next time some slick company tells you how accurate their AI model is, ask them if accuracy is really the most important thing. If they say, “Well, yes, of course,” then tell them about Cassandra.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Today I’m going to talk to you about a study at the cutting edge of modern medicine, one that uses an artificial intelligence (AI) model to guide care. But before I do, I need to take you back to the late Bronze Age, to a city located on the coast of what is now Turkey.
Troy’s towering walls made it seem unassailable, but that would not stop the Achaeans and their fleet of black ships from making landfall, and, after a siege, destroying the city. The destruction of Troy, as told in the Iliad and the Aeneid, was foretold by Cassandra, the daughter of King Priam and Priestess of Troy.
Cassandra had been given the gift of prophecy by the god Apollo in exchange for her favors. But after the gift was bestowed, she rejected the bright god and, in his rage, he added a curse to her blessing: that no one would ever believe her prophecies.
Thus it was that when her brother Paris set off to Sparta to abduct Helen, she warned him that his actions would lead to the downfall of their great city. He, of course, ignored her.
And you know the rest of the story.
Why am I telling you the story of Cassandra of Troy when we’re supposed to be talking about AI in medicine? Because AI has a major Cassandra problem.
The recent history of AI, and particularly the subset of AI known as machine learning in medicine, has been characterized by an accuracy arms race.
The electronic health record allows for the collection of volumes of data orders of magnitude greater than what we have ever been able to collect before. And all that data can be crunched by various algorithms to make predictions about, well, anything – whether a patient will be transferred to the intensive care unit, whether a GI bleed will need an intervention, whether someone will die in the next year.
Studies in this area tend to rely on retrospective datasets, and as time has gone on, better algorithms and more data have led to better and better predictions. In some simpler cases, machine-learning models have achieved near-perfect accuracy – Cassandra-level accuracy – as in the reading of chest x-rays for pneumonia, for example.
But as Cassandra teaches us, even perfect prediction is useless if no one believes you, if they don’t change their behavior. And this is the central problem of AI in medicine today. Many people are focusing on accuracy of the prediction but have forgotten that high accuracy is just table stakes for an AI model to be useful. It has to not only be accurate, but its use also has to change outcomes for patients. We need to be able to save Troy.
The best way to determine whether an AI model will help patients is to treat a model like we treat a new medication and evaluate it through a randomized trial. That’s what researchers, led by Shannon Walker of Vanderbilt University, Nashville, Tenn., did in a paper appearing in JAMA Network Open.
The model in question was one that predicted venous thromboembolism – blood clots – in hospitalized children. The model took in a variety of data points from the health record: a history of blood clot, history of cancer, presence of a central line, a variety of lab values. And the predictive model was very good – maybe not Cassandra good, but it achieved an AUC of 0.90, which means it had very high accuracy.
But again, accuracy is just table stakes.
The authors deployed the model in the live health record and recorded the results. For half of the kids, that was all that happened; no one actually saw the predictions. For those randomized to the intervention, the hematology team would be notified when the risk for clot was calculated to be greater than 2.5%. The hematology team would then contact the primary team to discuss prophylactic anticoagulation.
This is an elegant approach.
Let’s start with those table stakes – accuracy. The predictions were, by and large, pretty accurate in this trial. Of the 135 kids who developed blood clots, 121 had been flagged by the model in advance. That’s about 90%. The model flagged about 10% of kids who didn’t get a blood clot as well, but that’s not entirely surprising since the threshold for flagging was a 2.5% risk.
Given that the model preidentified almost every kid who would go on to develop a blood clot, it would make sense that kids randomized to the intervention would do better; after all, Cassandra was calling out her warnings.
But those kids didn’t do better. The rate of blood clot was no different between the group that used the accurate prediction model and the group that did not.
Why? Why does the use of an accurate model not necessarily improve outcomes?
First of all, a warning must lead to some change in management. Indeed, the kids in the intervention group were more likely to receive anticoagulation, but barely so. There were lots of reasons for this: physician preference, imminent discharge, active bleeding, and so on.
But let’s take a look at the 77 kids in the intervention arm who developed blood clots, because I think this is an instructive analysis.
Six of them did not meet the 2.5% threshold criteria, a case where the model missed its mark. Again, accuracy is table stakes.
Of the remaining 71, only 16 got a recommendation from the hematologist to start anticoagulation. Why not more? Well, the model identified some of the high-risk kids on the weekend, and it seems that the study team did not contact treatment teams during that time. That may account for about 40% of these cases. The remainder had some contraindication to anticoagulation.
Most tellingly, of the 16 who did get a recommendation to start anticoagulation, the recommendation was followed in only seven patients.
This is the gap between accurate prediction and the ability to change outcomes for patients. A prediction is useless if it is wrong, for sure. But it’s also useless if you don’t tell anyone about it. It’s useless if you tell someone but they can’t do anything about it. And it’s useless if they could do something about it but choose not to.
That’s the gulf that these models need to cross at this point. So, the next time some slick company tells you how accurate their AI model is, ask them if accuracy is really the most important thing. If they say, “Well, yes, of course,” then tell them about Cassandra.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
EMA warns that omega-3-acid ethyl esters may cause AFib
In its September meeting, the Should atrial fibrillation develop, intake of the medication must be stopped permanently.
Omega-3-acid ethyl esters are used to treat hypertriglyceridemia if lifestyle changes, particularly those related to nutrition, have not been sufficient to lower the blood triglyceride level. Hypertriglyceridemia is a risk factor for coronary heart disease.
During a Periodic Safety Update Single Assessment Procedure, the EMA safety committee analyzed systematic overviews and meta-analyses of randomized, controlled clinical studies. Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters, compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.
The PRAC will recommend an update to the Summary of Product Characteristics for preparations that contain omega-3-acid ethyl esters. The aim is to inform physicians, pharmacists, and patients of the risk for atrial fibrillation. A notification will be sent to health care professionals soon to inform them of further details.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
In its September meeting, the Should atrial fibrillation develop, intake of the medication must be stopped permanently.
Omega-3-acid ethyl esters are used to treat hypertriglyceridemia if lifestyle changes, particularly those related to nutrition, have not been sufficient to lower the blood triglyceride level. Hypertriglyceridemia is a risk factor for coronary heart disease.
During a Periodic Safety Update Single Assessment Procedure, the EMA safety committee analyzed systematic overviews and meta-analyses of randomized, controlled clinical studies. Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters, compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.
The PRAC will recommend an update to the Summary of Product Characteristics for preparations that contain omega-3-acid ethyl esters. The aim is to inform physicians, pharmacists, and patients of the risk for atrial fibrillation. A notification will be sent to health care professionals soon to inform them of further details.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
In its September meeting, the Should atrial fibrillation develop, intake of the medication must be stopped permanently.
Omega-3-acid ethyl esters are used to treat hypertriglyceridemia if lifestyle changes, particularly those related to nutrition, have not been sufficient to lower the blood triglyceride level. Hypertriglyceridemia is a risk factor for coronary heart disease.
During a Periodic Safety Update Single Assessment Procedure, the EMA safety committee analyzed systematic overviews and meta-analyses of randomized, controlled clinical studies. Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters, compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.
The PRAC will recommend an update to the Summary of Product Characteristics for preparations that contain omega-3-acid ethyl esters. The aim is to inform physicians, pharmacists, and patients of the risk for atrial fibrillation. A notification will be sent to health care professionals soon to inform them of further details.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
Updated pleural disease guidelines from the British Thoracic Society
Thoracic Oncology & Chest Imaging Network
Pleural Disease Section
After more than a decade, the British Thoracic Society (BTS) released updated guidelines for pleural disease (Roberts ME , et al. Thorax 2023; 78, s1-s42). Their focus includes spontaneous pneumothorax, undiagnosed unilateral pleural effusion, pleural infections, and malignant pleural effusion (MPE). Separate statements for pleural procedures (Asciak R et al. Thorax. 2023;78:s43-s68) and pleural mesothelioma (Woolhouse I et al. Thorax. 2018;73:i1-i30) are available.
Major highlights of the recommendations are as follows:
- Conservative management can be considered for minimally symptomatic primary spontaneous pneumothorax regardless of size. A multi-disciplinary approach and shared decision-making is vital, especially when deciding between needle aspiration, intercostal drainage or ambulatory devices. Special recommendations were for pregnancy, cystic fibrosis, catamenial, iatrogenic and familial.
- Undiagnosed unilateral pleural effusion. Besides pleural fluid studies, in those with unclear etiology, thoracoscopic or image-guided pleural biopsy is recommended.
- Pleural infection. Use of renal, age, purulence, infection source, dietary factors (RAPID) scoring may be considered for risk stratification. Drainage of the pleural space with catheter and intrapleural therapy with combination tissue plasminogen activator (TPA) and DNAse in residual pleural fluid should be considered. Medical thoracoscopy not supported due to lack of evidence.
- MPE. Definitive pleural intervention based on symptoms and shared decision making was supported. Modality may include talc slurry via chest tube, talc poudrage via thoracoscopy or talc instillation via indwelling pleural catheter. Intrapleural chemotherapy should not be routinely used for treatment of MPE.
These guidelines provide a comprehensive consensus to the literature and reinforce prior recommendations of other professional societies (Gilbert CR et al. Chest. 2020;158:2221-8. Miller RJ et al.; J Bronchology Interv Pulmonol. 2020;27[4]:229-45. Feller-Kopman DJ et al.; Am J Respir Crit Care Med. 2018;198:839-49).
Munish Sharma, MD
Hiren Mehta, MD, Section Member-at-Large
Philip Ong, MD, Section Member-at-Large
Thoracic Oncology & Chest Imaging Network
Pleural Disease Section
After more than a decade, the British Thoracic Society (BTS) released updated guidelines for pleural disease (Roberts ME , et al. Thorax 2023; 78, s1-s42). Their focus includes spontaneous pneumothorax, undiagnosed unilateral pleural effusion, pleural infections, and malignant pleural effusion (MPE). Separate statements for pleural procedures (Asciak R et al. Thorax. 2023;78:s43-s68) and pleural mesothelioma (Woolhouse I et al. Thorax. 2018;73:i1-i30) are available.
Major highlights of the recommendations are as follows:
- Conservative management can be considered for minimally symptomatic primary spontaneous pneumothorax regardless of size. A multi-disciplinary approach and shared decision-making is vital, especially when deciding between needle aspiration, intercostal drainage or ambulatory devices. Special recommendations were for pregnancy, cystic fibrosis, catamenial, iatrogenic and familial.
- Undiagnosed unilateral pleural effusion. Besides pleural fluid studies, in those with unclear etiology, thoracoscopic or image-guided pleural biopsy is recommended.
- Pleural infection. Use of renal, age, purulence, infection source, dietary factors (RAPID) scoring may be considered for risk stratification. Drainage of the pleural space with catheter and intrapleural therapy with combination tissue plasminogen activator (TPA) and DNAse in residual pleural fluid should be considered. Medical thoracoscopy not supported due to lack of evidence.
- MPE. Definitive pleural intervention based on symptoms and shared decision making was supported. Modality may include talc slurry via chest tube, talc poudrage via thoracoscopy or talc instillation via indwelling pleural catheter. Intrapleural chemotherapy should not be routinely used for treatment of MPE.
These guidelines provide a comprehensive consensus to the literature and reinforce prior recommendations of other professional societies (Gilbert CR et al. Chest. 2020;158:2221-8. Miller RJ et al.; J Bronchology Interv Pulmonol. 2020;27[4]:229-45. Feller-Kopman DJ et al.; Am J Respir Crit Care Med. 2018;198:839-49).
Munish Sharma, MD
Hiren Mehta, MD, Section Member-at-Large
Philip Ong, MD, Section Member-at-Large
Thoracic Oncology & Chest Imaging Network
Pleural Disease Section
After more than a decade, the British Thoracic Society (BTS) released updated guidelines for pleural disease (Roberts ME , et al. Thorax 2023; 78, s1-s42). Their focus includes spontaneous pneumothorax, undiagnosed unilateral pleural effusion, pleural infections, and malignant pleural effusion (MPE). Separate statements for pleural procedures (Asciak R et al. Thorax. 2023;78:s43-s68) and pleural mesothelioma (Woolhouse I et al. Thorax. 2018;73:i1-i30) are available.
Major highlights of the recommendations are as follows:
- Conservative management can be considered for minimally symptomatic primary spontaneous pneumothorax regardless of size. A multi-disciplinary approach and shared decision-making is vital, especially when deciding between needle aspiration, intercostal drainage or ambulatory devices. Special recommendations were for pregnancy, cystic fibrosis, catamenial, iatrogenic and familial.
- Undiagnosed unilateral pleural effusion. Besides pleural fluid studies, in those with unclear etiology, thoracoscopic or image-guided pleural biopsy is recommended.
- Pleural infection. Use of renal, age, purulence, infection source, dietary factors (RAPID) scoring may be considered for risk stratification. Drainage of the pleural space with catheter and intrapleural therapy with combination tissue plasminogen activator (TPA) and DNAse in residual pleural fluid should be considered. Medical thoracoscopy not supported due to lack of evidence.
- MPE. Definitive pleural intervention based on symptoms and shared decision making was supported. Modality may include talc slurry via chest tube, talc poudrage via thoracoscopy or talc instillation via indwelling pleural catheter. Intrapleural chemotherapy should not be routinely used for treatment of MPE.
These guidelines provide a comprehensive consensus to the literature and reinforce prior recommendations of other professional societies (Gilbert CR et al. Chest. 2020;158:2221-8. Miller RJ et al.; J Bronchology Interv Pulmonol. 2020;27[4]:229-45. Feller-Kopman DJ et al.; Am J Respir Crit Care Med. 2018;198:839-49).
Munish Sharma, MD
Hiren Mehta, MD, Section Member-at-Large
Philip Ong, MD, Section Member-at-Large
Rare disease roundup
Can a repurposed Parkinson’s drug slow ALS progression?
Ropinirole, a drug used for Parkinson’s disease, shows promise in slowing the progression of amyotrophic lateral sclerosis (ALS), early research suggests.
Investigators randomly assigned 20 individuals with sporadic ALS to receive either ropinirole or placebo for 24 weeks. During the double-blind period, there was no difference between the groups in terms of decline in functional status.
However, during a further open-label extension period, the ropinirole group showed significant suppression of functional decline and an average of an additional 7 months of progression-free survival.
The researchers were able to predict clinical responsiveness to ropinirole in vitro by analyzing motor neurons derived from participants’ stem cells.
The study was published online in Cell Stem Cell (2023 Jun 1. doi: 10.1016/j.stem.2023.04.017).
The trial was sponsored by K Pharma. The study drug, active drugs, and placebo were supplied free of charge by GlaxoSmithKline.
West Nile infections rising in the U.S.
Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States. West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.
West Nile Virus is the leading cause of mosquito-borne disease in the continental United States. As of Aug. 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention.
“Particularly here in California, it’s peak risk right now,” said Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health. She said scientists there are seeing higher mosquito and infected mosquito numbers.
Dead birds are tested for the virus and by Aug. 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by that time in 2022.
“Last year at this time, we had 60 positive dead birds out of 817 tested,” Dr. Kramer said.
Myasthenia gravis drug gets FDA nod
The Food and Drug Administration (FDA) has approved rozanolixizumab (Rystiggo, UCB) to treat adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody, the drug’s manufacturer, UCB, has announced.
gMG is a rare autoimmune disease of the nerve muscle junction. Anti-AChR and anti-MuSK antibody-positive gMG are the two most common subtypes. Rozanolixizumab is the first FDA-approved treatment for adults with both subtypes.
Rozanolixizumab is a subcutaneous-infused humanized IgG4 monoclonal antibody that binds to the neonatal Fc
receptor (FcRn), reducing the concentration of pathogenic IgG autoantibodies.
U.S. approval is based on results of the phase 3
MycarinG study involving 200 patients with AChR or MuSK autoantibody-positive gMG. Patients were randomly assigned to one of two rozanolixizumab groups (7 mg/kg or 10 mg/kg) or placebo for 6 weeks.
As reported in The Lancet Neurology (2023 May. doi: 10.1016/S1474-4422[23]00077-7), rozanolixizumab led to statistically significant improvements in gMG-specific outcomes, including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair.
Gene therapy promising for reversal of hereditary vision loss
An unapproved gene therapy for Leber hereditary optic neuropathy (LHON) led to a marked improvement in the eyesight of patients with a severe, progressive form of the disease who received the therapy as part of an early access program.
Results of a study of more than 60 patients who received lenadogene nolparvovec (Lumevoq, GenSight Biologics) as a unilateral or bilateral intravitreal injection showed that, at 2-year follow-up, 60% had experienced a clinically relevant improvement in the number of letters they could read on a visual acuity chart.
The results, said study presenter Chiara La Morgia, MD, PhD, IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy), confirm in a “real-life setting” the efficacy and safety of the treatment as previously shown in clinical trials.
The findings were presented at the 2023 Congress of the European Academy of Neurology.
No funding was declared. Dr. La Morgia has relationships with Chiesi Farmaceutici, GenSight Biologics, Regulatory Pharma Net, Thenewway, Santhera Pharmaceuticals, First Class, Biologix, Stoke Therapeutics, and Reneo.
FDA OKs new drug for Fabry disease
The FDA has approved pegunigalsidase alfa (Elfabrio, Chiesi Global Rare Diseases/Protalix BioTherapeutics), an enzyme replacement therapy (ERT) to treat adults with Fabry disease.
Fabry disease is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme alpha-galactosidase A (GLA), which leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.
Elfabrio delivers a functional version of GLA. It is given by intravenous infusion every 2 weeks.
Evidence for safety, tolerability, and efficacy of Elfabrio stem from a comprehensive clinical program in more than 140 patients with up to 7.5 years of follow-up treatment.
It has been studied in both ERT-naive and ERT-experienced patients. In one head-to-head trial, Elfabrio was noninferior in safety and efficacy to agalsidase beta (Fabrazyme, Sanofi Genzyme), the companies said in a press statement announcing approval.
U.S. incidence, prevalence of myasthenia gravis are rising
There has been an increase in the incidence and prevalence of myasthenia gravis in the United States, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be caused by “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” said study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.
Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.
Funding for the study was provided by Alexion, AstraZeneca Rare
Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases.
Novel agent offers hope for hereditary ATTR polyneuropathy in pivotal trial
The investigational agent eplontersen (Ionis Pharmaceuticals/AstraZeneca) halted neuropathy disease progression and improved neuropathy impairment and quality of life for patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) in a pivotal phase 3 trial.
Eplontersen led to “clinically and statistically significant benefits at week 66 with an early and rapid sustained reduction in serum TTR [transthyretin] concentration, a halting of the progression of the neuropathy impairment, and a trend to improvement in quality of life,” said principal investigator Sami Khella, MD, professor of clinical neurology at the University of Pennsylvania, Philadelphia.
Dr. Khella reported final data from the NEURO-TTRansform trial at the annual meeting of the American Academy of Neurology.
The FDA has accepted a new drug application for eplontersen for the treatment of ATTRv-PN. The drug has a Prescription Drug User Fee Act date of Dec. 22, 2023. Eplontersen has orphan drug designation in the United States.
The study was sponsored by Ionis Pharmaceuticals. Dr. Khella has relationships with Ionis, Pfizer, Alnylam, and Eidos.
FDA gives fast-track approval to new ALS drug
The FDA has approved the first treatment that takes a genetics-based approach to slowing or stopping the progression of a rare form of amyotrophic lateral sclerosis (ALS).
The FDA fast-tracked the approval of Qalsody (Biogen) based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.
Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.
The new treatment is approved only for people with SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.
FDA OKs first treatment for Friedreich ataxia
The FDA has approved the first treatment for the neurodegenerative disorder Friedreich ataxia for use in adults and adolescents aged 16 and older.
The recommended dose of omaveloxolone (Skyclarys, Reata Pharmaceuticals) is 150 mg (three capsules) taken orally once daily on an empty stomach.
The FDA approval of omaveloxolone was supported by a randomized double-blind, placebo-controlled study comprising 103 patients with genetically confirmed Friedreich ataxia and baseline modified Friedreich Ataxia Rating Scale (mFARS) scores between 20 and 80.
Treatment with the novel medication led to statistically significant lower mFARS scores, signifying less impairment, relative to placebo, at week 48. The placebo-corrected difference between the two groups was –2.41 points (P = .0138).
Omaveloxolone received priority review and had orphan drug, fast track, and rare pediatric disease designations.
FDA OKs first drug for Rett syndrome
The FDA has approved trofinetide oral solution (Daybue, Acadia Pharmaceuticals) as the first treatment of Rett syndrome in adults and children aged 2 years and older.
Trofinetide is a synthetic analogue of the amino-terminal tripeptide of insulinlike growth factor-1, which occurs naturally in the brain. The drug is designed to treat the core symptoms of Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function.
The approval of trofinetide was supported by results from the pivotal phase 3 LAVENDER study that tested the efficacy and safety of trofinetide versus placebo in 187 female patients with Rett syndrome, aged 5-20 years.
More data back Guillain-Barré risk with Janssen COVID shot
New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) back previous findings of increased risk for Guillain-Barré syndrome (GBS) after receiving the Janssen COVID-19 vaccine (Ad26.COV2.S).
Over 14 months, GBS reporting rates within 21 and 42 days of administration of Janssen’s replication-incompetent adenoviral vector vaccine were approximately 9-12 times higher than after administration of the Pfizer-BioNTech (BNT162b2) or the Moderna (mRNA-1273) mRNA COVID vaccines.
Additionally, observed GBS cases after the Janssen shot were two to three times greater than expected, based on background rates within 21 and 42 days of vaccination.
Conversely, and confirming prior data, there was no increased risk for GBS with the Pfizer or Moderna vaccines and no significant difference between observed and expected numbers of GBS cases after either mRNA COVID-19 vaccine.
The findings were published online in JAMA Network Open (2023 Feb 1. doi: 10.1001/jamanetworkopen.2022.53845).
Diazepam nasal spray effective in Lennox-Gastaut syndrome
A new analysis of data from a phase 3 clinical trial suggests that an inhaled diazepam nasal spray (Valtoco, Neurelis) works about as well among patients with Lennox-Gastaut syndrome (LGS) as it does with other patients with pediatric encephalopathies.
LGS is a severe form of epilepsy that generally begins in early childhood and has a poor prognosis and seizures that are often treatment refractory. The findings of the analysis should be encouraging to physicians who may view patients with LGS as not benefiting from treatment, said Daniel C. Tarquinio, DO, who presented the results at the 2022 annual meeting of the Child Neurology Society.
Novel cannabis oil curbs tics in severe Tourette syndrome
An oral oil containing tetrahydrocannabinol (THC) and cannabidiol (CBD) led to a significant and meaningful reduction in motor and vocal tics in patients with severe Tourette syndrome, results of a double-blind, placebo-controlled, crossover study showed.
“In a methodologically robust manner (and independent of any drug company sponsorship), we provide evidence for the effectiveness of repeated dosing with THC:CBD versus placebo in tic
suppression, as well as reduction of comorbid anxiety and obsessive-compulsive disorder in severe Tourette syndrome,” neuropsychiatrist and lead investigator Philip Mosley, PhD, said in an interview.
The results offer support to people with Tourette syndrome who “want to approach their doctor to try medicinal cannabis when other drugs have not worked or are intolerable,” said
Dr. Mosley, of the Wesley Research Institute and QIMR Berghofer Medical Research Institute, Herston, Australia.
The study was published online in NEJM Evidence (2023 Jun 7. doi: 10.1056/EVIDoa2300012).
Twenty-two adults (mean age, 31 years) with severe Tourette syndrome received THC:CBD oil titrated upward over 6 weeks to a daily dose of 20 mg of THC and 20 mg of CBD, followed by a 6-week course of placebo (or vice versa). Six participants had not previously used cannabis.
The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range, 0-50 with higher scores = greater tic severity).
The mean baseline YGTSS total tic score was 35.7. At 6 weeks, the reduction in total tic score was 8.9 with THC:CBD versus 2.5 with placebo.
A linear mixed-effects model (intention to treat) showed a significant interaction of treatment and visit number (P = .008), indicating a greater decrease (improvement) in tic score over time with THC:CBD, the study team reported.
On average, the magnitude of the tic reduction was “moderate” and comparable with the effect observed with existing treatments such as antipsychotic agents, the investigators noted.
The study was funded by the Wesley Medical Research Institute, Brisbane, and the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded research organization at the University of Sydney, Australia.
Dr. Mosley reported no relevant financial relationships.
Can a repurposed Parkinson’s drug slow ALS progression?
Ropinirole, a drug used for Parkinson’s disease, shows promise in slowing the progression of amyotrophic lateral sclerosis (ALS), early research suggests.
Investigators randomly assigned 20 individuals with sporadic ALS to receive either ropinirole or placebo for 24 weeks. During the double-blind period, there was no difference between the groups in terms of decline in functional status.
However, during a further open-label extension period, the ropinirole group showed significant suppression of functional decline and an average of an additional 7 months of progression-free survival.
The researchers were able to predict clinical responsiveness to ropinirole in vitro by analyzing motor neurons derived from participants’ stem cells.
The study was published online in Cell Stem Cell (2023 Jun 1. doi: 10.1016/j.stem.2023.04.017).
The trial was sponsored by K Pharma. The study drug, active drugs, and placebo were supplied free of charge by GlaxoSmithKline.
West Nile infections rising in the U.S.
Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States. West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.
West Nile Virus is the leading cause of mosquito-borne disease in the continental United States. As of Aug. 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention.
“Particularly here in California, it’s peak risk right now,” said Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health. She said scientists there are seeing higher mosquito and infected mosquito numbers.
Dead birds are tested for the virus and by Aug. 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by that time in 2022.
“Last year at this time, we had 60 positive dead birds out of 817 tested,” Dr. Kramer said.
Myasthenia gravis drug gets FDA nod
The Food and Drug Administration (FDA) has approved rozanolixizumab (Rystiggo, UCB) to treat adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody, the drug’s manufacturer, UCB, has announced.
gMG is a rare autoimmune disease of the nerve muscle junction. Anti-AChR and anti-MuSK antibody-positive gMG are the two most common subtypes. Rozanolixizumab is the first FDA-approved treatment for adults with both subtypes.
Rozanolixizumab is a subcutaneous-infused humanized IgG4 monoclonal antibody that binds to the neonatal Fc
receptor (FcRn), reducing the concentration of pathogenic IgG autoantibodies.
U.S. approval is based on results of the phase 3
MycarinG study involving 200 patients with AChR or MuSK autoantibody-positive gMG. Patients were randomly assigned to one of two rozanolixizumab groups (7 mg/kg or 10 mg/kg) or placebo for 6 weeks.
As reported in The Lancet Neurology (2023 May. doi: 10.1016/S1474-4422[23]00077-7), rozanolixizumab led to statistically significant improvements in gMG-specific outcomes, including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair.
Gene therapy promising for reversal of hereditary vision loss
An unapproved gene therapy for Leber hereditary optic neuropathy (LHON) led to a marked improvement in the eyesight of patients with a severe, progressive form of the disease who received the therapy as part of an early access program.
Results of a study of more than 60 patients who received lenadogene nolparvovec (Lumevoq, GenSight Biologics) as a unilateral or bilateral intravitreal injection showed that, at 2-year follow-up, 60% had experienced a clinically relevant improvement in the number of letters they could read on a visual acuity chart.
The results, said study presenter Chiara La Morgia, MD, PhD, IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy), confirm in a “real-life setting” the efficacy and safety of the treatment as previously shown in clinical trials.
The findings were presented at the 2023 Congress of the European Academy of Neurology.
No funding was declared. Dr. La Morgia has relationships with Chiesi Farmaceutici, GenSight Biologics, Regulatory Pharma Net, Thenewway, Santhera Pharmaceuticals, First Class, Biologix, Stoke Therapeutics, and Reneo.
FDA OKs new drug for Fabry disease
The FDA has approved pegunigalsidase alfa (Elfabrio, Chiesi Global Rare Diseases/Protalix BioTherapeutics), an enzyme replacement therapy (ERT) to treat adults with Fabry disease.
Fabry disease is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme alpha-galactosidase A (GLA), which leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.
Elfabrio delivers a functional version of GLA. It is given by intravenous infusion every 2 weeks.
Evidence for safety, tolerability, and efficacy of Elfabrio stem from a comprehensive clinical program in more than 140 patients with up to 7.5 years of follow-up treatment.
It has been studied in both ERT-naive and ERT-experienced patients. In one head-to-head trial, Elfabrio was noninferior in safety and efficacy to agalsidase beta (Fabrazyme, Sanofi Genzyme), the companies said in a press statement announcing approval.
U.S. incidence, prevalence of myasthenia gravis are rising
There has been an increase in the incidence and prevalence of myasthenia gravis in the United States, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be caused by “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” said study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.
Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.
Funding for the study was provided by Alexion, AstraZeneca Rare
Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases.
Novel agent offers hope for hereditary ATTR polyneuropathy in pivotal trial
The investigational agent eplontersen (Ionis Pharmaceuticals/AstraZeneca) halted neuropathy disease progression and improved neuropathy impairment and quality of life for patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) in a pivotal phase 3 trial.
Eplontersen led to “clinically and statistically significant benefits at week 66 with an early and rapid sustained reduction in serum TTR [transthyretin] concentration, a halting of the progression of the neuropathy impairment, and a trend to improvement in quality of life,” said principal investigator Sami Khella, MD, professor of clinical neurology at the University of Pennsylvania, Philadelphia.
Dr. Khella reported final data from the NEURO-TTRansform trial at the annual meeting of the American Academy of Neurology.
The FDA has accepted a new drug application for eplontersen for the treatment of ATTRv-PN. The drug has a Prescription Drug User Fee Act date of Dec. 22, 2023. Eplontersen has orphan drug designation in the United States.
The study was sponsored by Ionis Pharmaceuticals. Dr. Khella has relationships with Ionis, Pfizer, Alnylam, and Eidos.
FDA gives fast-track approval to new ALS drug
The FDA has approved the first treatment that takes a genetics-based approach to slowing or stopping the progression of a rare form of amyotrophic lateral sclerosis (ALS).
The FDA fast-tracked the approval of Qalsody (Biogen) based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.
Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.
The new treatment is approved only for people with SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.
FDA OKs first treatment for Friedreich ataxia
The FDA has approved the first treatment for the neurodegenerative disorder Friedreich ataxia for use in adults and adolescents aged 16 and older.
The recommended dose of omaveloxolone (Skyclarys, Reata Pharmaceuticals) is 150 mg (three capsules) taken orally once daily on an empty stomach.
The FDA approval of omaveloxolone was supported by a randomized double-blind, placebo-controlled study comprising 103 patients with genetically confirmed Friedreich ataxia and baseline modified Friedreich Ataxia Rating Scale (mFARS) scores between 20 and 80.
Treatment with the novel medication led to statistically significant lower mFARS scores, signifying less impairment, relative to placebo, at week 48. The placebo-corrected difference between the two groups was –2.41 points (P = .0138).
Omaveloxolone received priority review and had orphan drug, fast track, and rare pediatric disease designations.
FDA OKs first drug for Rett syndrome
The FDA has approved trofinetide oral solution (Daybue, Acadia Pharmaceuticals) as the first treatment of Rett syndrome in adults and children aged 2 years and older.
Trofinetide is a synthetic analogue of the amino-terminal tripeptide of insulinlike growth factor-1, which occurs naturally in the brain. The drug is designed to treat the core symptoms of Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function.
The approval of trofinetide was supported by results from the pivotal phase 3 LAVENDER study that tested the efficacy and safety of trofinetide versus placebo in 187 female patients with Rett syndrome, aged 5-20 years.
More data back Guillain-Barré risk with Janssen COVID shot
New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) back previous findings of increased risk for Guillain-Barré syndrome (GBS) after receiving the Janssen COVID-19 vaccine (Ad26.COV2.S).
Over 14 months, GBS reporting rates within 21 and 42 days of administration of Janssen’s replication-incompetent adenoviral vector vaccine were approximately 9-12 times higher than after administration of the Pfizer-BioNTech (BNT162b2) or the Moderna (mRNA-1273) mRNA COVID vaccines.
Additionally, observed GBS cases after the Janssen shot were two to three times greater than expected, based on background rates within 21 and 42 days of vaccination.
Conversely, and confirming prior data, there was no increased risk for GBS with the Pfizer or Moderna vaccines and no significant difference between observed and expected numbers of GBS cases after either mRNA COVID-19 vaccine.
The findings were published online in JAMA Network Open (2023 Feb 1. doi: 10.1001/jamanetworkopen.2022.53845).
Diazepam nasal spray effective in Lennox-Gastaut syndrome
A new analysis of data from a phase 3 clinical trial suggests that an inhaled diazepam nasal spray (Valtoco, Neurelis) works about as well among patients with Lennox-Gastaut syndrome (LGS) as it does with other patients with pediatric encephalopathies.
LGS is a severe form of epilepsy that generally begins in early childhood and has a poor prognosis and seizures that are often treatment refractory. The findings of the analysis should be encouraging to physicians who may view patients with LGS as not benefiting from treatment, said Daniel C. Tarquinio, DO, who presented the results at the 2022 annual meeting of the Child Neurology Society.
Novel cannabis oil curbs tics in severe Tourette syndrome
An oral oil containing tetrahydrocannabinol (THC) and cannabidiol (CBD) led to a significant and meaningful reduction in motor and vocal tics in patients with severe Tourette syndrome, results of a double-blind, placebo-controlled, crossover study showed.
“In a methodologically robust manner (and independent of any drug company sponsorship), we provide evidence for the effectiveness of repeated dosing with THC:CBD versus placebo in tic
suppression, as well as reduction of comorbid anxiety and obsessive-compulsive disorder in severe Tourette syndrome,” neuropsychiatrist and lead investigator Philip Mosley, PhD, said in an interview.
The results offer support to people with Tourette syndrome who “want to approach their doctor to try medicinal cannabis when other drugs have not worked or are intolerable,” said
Dr. Mosley, of the Wesley Research Institute and QIMR Berghofer Medical Research Institute, Herston, Australia.
The study was published online in NEJM Evidence (2023 Jun 7. doi: 10.1056/EVIDoa2300012).
Twenty-two adults (mean age, 31 years) with severe Tourette syndrome received THC:CBD oil titrated upward over 6 weeks to a daily dose of 20 mg of THC and 20 mg of CBD, followed by a 6-week course of placebo (or vice versa). Six participants had not previously used cannabis.
The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range, 0-50 with higher scores = greater tic severity).
The mean baseline YGTSS total tic score was 35.7. At 6 weeks, the reduction in total tic score was 8.9 with THC:CBD versus 2.5 with placebo.
A linear mixed-effects model (intention to treat) showed a significant interaction of treatment and visit number (P = .008), indicating a greater decrease (improvement) in tic score over time with THC:CBD, the study team reported.
On average, the magnitude of the tic reduction was “moderate” and comparable with the effect observed with existing treatments such as antipsychotic agents, the investigators noted.
The study was funded by the Wesley Medical Research Institute, Brisbane, and the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded research organization at the University of Sydney, Australia.
Dr. Mosley reported no relevant financial relationships.
Can a repurposed Parkinson’s drug slow ALS progression?
Ropinirole, a drug used for Parkinson’s disease, shows promise in slowing the progression of amyotrophic lateral sclerosis (ALS), early research suggests.
Investigators randomly assigned 20 individuals with sporadic ALS to receive either ropinirole or placebo for 24 weeks. During the double-blind period, there was no difference between the groups in terms of decline in functional status.
However, during a further open-label extension period, the ropinirole group showed significant suppression of functional decline and an average of an additional 7 months of progression-free survival.
The researchers were able to predict clinical responsiveness to ropinirole in vitro by analyzing motor neurons derived from participants’ stem cells.
The study was published online in Cell Stem Cell (2023 Jun 1. doi: 10.1016/j.stem.2023.04.017).
The trial was sponsored by K Pharma. The study drug, active drugs, and placebo were supplied free of charge by GlaxoSmithKline.
West Nile infections rising in the U.S.
Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States. West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.
West Nile Virus is the leading cause of mosquito-borne disease in the continental United States. As of Aug. 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention.
“Particularly here in California, it’s peak risk right now,” said Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health. She said scientists there are seeing higher mosquito and infected mosquito numbers.
Dead birds are tested for the virus and by Aug. 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by that time in 2022.
“Last year at this time, we had 60 positive dead birds out of 817 tested,” Dr. Kramer said.
Myasthenia gravis drug gets FDA nod
The Food and Drug Administration (FDA) has approved rozanolixizumab (Rystiggo, UCB) to treat adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody, the drug’s manufacturer, UCB, has announced.
gMG is a rare autoimmune disease of the nerve muscle junction. Anti-AChR and anti-MuSK antibody-positive gMG are the two most common subtypes. Rozanolixizumab is the first FDA-approved treatment for adults with both subtypes.
Rozanolixizumab is a subcutaneous-infused humanized IgG4 monoclonal antibody that binds to the neonatal Fc
receptor (FcRn), reducing the concentration of pathogenic IgG autoantibodies.
U.S. approval is based on results of the phase 3
MycarinG study involving 200 patients with AChR or MuSK autoantibody-positive gMG. Patients were randomly assigned to one of two rozanolixizumab groups (7 mg/kg or 10 mg/kg) or placebo for 6 weeks.
As reported in The Lancet Neurology (2023 May. doi: 10.1016/S1474-4422[23]00077-7), rozanolixizumab led to statistically significant improvements in gMG-specific outcomes, including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair.
Gene therapy promising for reversal of hereditary vision loss
An unapproved gene therapy for Leber hereditary optic neuropathy (LHON) led to a marked improvement in the eyesight of patients with a severe, progressive form of the disease who received the therapy as part of an early access program.
Results of a study of more than 60 patients who received lenadogene nolparvovec (Lumevoq, GenSight Biologics) as a unilateral or bilateral intravitreal injection showed that, at 2-year follow-up, 60% had experienced a clinically relevant improvement in the number of letters they could read on a visual acuity chart.
The results, said study presenter Chiara La Morgia, MD, PhD, IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy), confirm in a “real-life setting” the efficacy and safety of the treatment as previously shown in clinical trials.
The findings were presented at the 2023 Congress of the European Academy of Neurology.
No funding was declared. Dr. La Morgia has relationships with Chiesi Farmaceutici, GenSight Biologics, Regulatory Pharma Net, Thenewway, Santhera Pharmaceuticals, First Class, Biologix, Stoke Therapeutics, and Reneo.
FDA OKs new drug for Fabry disease
The FDA has approved pegunigalsidase alfa (Elfabrio, Chiesi Global Rare Diseases/Protalix BioTherapeutics), an enzyme replacement therapy (ERT) to treat adults with Fabry disease.
Fabry disease is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme alpha-galactosidase A (GLA), which leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.
Elfabrio delivers a functional version of GLA. It is given by intravenous infusion every 2 weeks.
Evidence for safety, tolerability, and efficacy of Elfabrio stem from a comprehensive clinical program in more than 140 patients with up to 7.5 years of follow-up treatment.
It has been studied in both ERT-naive and ERT-experienced patients. In one head-to-head trial, Elfabrio was noninferior in safety and efficacy to agalsidase beta (Fabrazyme, Sanofi Genzyme), the companies said in a press statement announcing approval.
U.S. incidence, prevalence of myasthenia gravis are rising
There has been an increase in the incidence and prevalence of myasthenia gravis in the United States, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be caused by “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” said study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.
Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.
Funding for the study was provided by Alexion, AstraZeneca Rare
Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases.
Novel agent offers hope for hereditary ATTR polyneuropathy in pivotal trial
The investigational agent eplontersen (Ionis Pharmaceuticals/AstraZeneca) halted neuropathy disease progression and improved neuropathy impairment and quality of life for patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) in a pivotal phase 3 trial.
Eplontersen led to “clinically and statistically significant benefits at week 66 with an early and rapid sustained reduction in serum TTR [transthyretin] concentration, a halting of the progression of the neuropathy impairment, and a trend to improvement in quality of life,” said principal investigator Sami Khella, MD, professor of clinical neurology at the University of Pennsylvania, Philadelphia.
Dr. Khella reported final data from the NEURO-TTRansform trial at the annual meeting of the American Academy of Neurology.
The FDA has accepted a new drug application for eplontersen for the treatment of ATTRv-PN. The drug has a Prescription Drug User Fee Act date of Dec. 22, 2023. Eplontersen has orphan drug designation in the United States.
The study was sponsored by Ionis Pharmaceuticals. Dr. Khella has relationships with Ionis, Pfizer, Alnylam, and Eidos.
FDA gives fast-track approval to new ALS drug
The FDA has approved the first treatment that takes a genetics-based approach to slowing or stopping the progression of a rare form of amyotrophic lateral sclerosis (ALS).
The FDA fast-tracked the approval of Qalsody (Biogen) based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.
Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.
The new treatment is approved only for people with SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.
FDA OKs first treatment for Friedreich ataxia
The FDA has approved the first treatment for the neurodegenerative disorder Friedreich ataxia for use in adults and adolescents aged 16 and older.
The recommended dose of omaveloxolone (Skyclarys, Reata Pharmaceuticals) is 150 mg (three capsules) taken orally once daily on an empty stomach.
The FDA approval of omaveloxolone was supported by a randomized double-blind, placebo-controlled study comprising 103 patients with genetically confirmed Friedreich ataxia and baseline modified Friedreich Ataxia Rating Scale (mFARS) scores between 20 and 80.
Treatment with the novel medication led to statistically significant lower mFARS scores, signifying less impairment, relative to placebo, at week 48. The placebo-corrected difference between the two groups was –2.41 points (P = .0138).
Omaveloxolone received priority review and had orphan drug, fast track, and rare pediatric disease designations.
FDA OKs first drug for Rett syndrome
The FDA has approved trofinetide oral solution (Daybue, Acadia Pharmaceuticals) as the first treatment of Rett syndrome in adults and children aged 2 years and older.
Trofinetide is a synthetic analogue of the amino-terminal tripeptide of insulinlike growth factor-1, which occurs naturally in the brain. The drug is designed to treat the core symptoms of Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function.
The approval of trofinetide was supported by results from the pivotal phase 3 LAVENDER study that tested the efficacy and safety of trofinetide versus placebo in 187 female patients with Rett syndrome, aged 5-20 years.
More data back Guillain-Barré risk with Janssen COVID shot
New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) back previous findings of increased risk for Guillain-Barré syndrome (GBS) after receiving the Janssen COVID-19 vaccine (Ad26.COV2.S).
Over 14 months, GBS reporting rates within 21 and 42 days of administration of Janssen’s replication-incompetent adenoviral vector vaccine were approximately 9-12 times higher than after administration of the Pfizer-BioNTech (BNT162b2) or the Moderna (mRNA-1273) mRNA COVID vaccines.
Additionally, observed GBS cases after the Janssen shot were two to three times greater than expected, based on background rates within 21 and 42 days of vaccination.
Conversely, and confirming prior data, there was no increased risk for GBS with the Pfizer or Moderna vaccines and no significant difference between observed and expected numbers of GBS cases after either mRNA COVID-19 vaccine.
The findings were published online in JAMA Network Open (2023 Feb 1. doi: 10.1001/jamanetworkopen.2022.53845).
Diazepam nasal spray effective in Lennox-Gastaut syndrome
A new analysis of data from a phase 3 clinical trial suggests that an inhaled diazepam nasal spray (Valtoco, Neurelis) works about as well among patients with Lennox-Gastaut syndrome (LGS) as it does with other patients with pediatric encephalopathies.
LGS is a severe form of epilepsy that generally begins in early childhood and has a poor prognosis and seizures that are often treatment refractory. The findings of the analysis should be encouraging to physicians who may view patients with LGS as not benefiting from treatment, said Daniel C. Tarquinio, DO, who presented the results at the 2022 annual meeting of the Child Neurology Society.
Novel cannabis oil curbs tics in severe Tourette syndrome
An oral oil containing tetrahydrocannabinol (THC) and cannabidiol (CBD) led to a significant and meaningful reduction in motor and vocal tics in patients with severe Tourette syndrome, results of a double-blind, placebo-controlled, crossover study showed.
“In a methodologically robust manner (and independent of any drug company sponsorship), we provide evidence for the effectiveness of repeated dosing with THC:CBD versus placebo in tic
suppression, as well as reduction of comorbid anxiety and obsessive-compulsive disorder in severe Tourette syndrome,” neuropsychiatrist and lead investigator Philip Mosley, PhD, said in an interview.
The results offer support to people with Tourette syndrome who “want to approach their doctor to try medicinal cannabis when other drugs have not worked or are intolerable,” said
Dr. Mosley, of the Wesley Research Institute and QIMR Berghofer Medical Research Institute, Herston, Australia.
The study was published online in NEJM Evidence (2023 Jun 7. doi: 10.1056/EVIDoa2300012).
Twenty-two adults (mean age, 31 years) with severe Tourette syndrome received THC:CBD oil titrated upward over 6 weeks to a daily dose of 20 mg of THC and 20 mg of CBD, followed by a 6-week course of placebo (or vice versa). Six participants had not previously used cannabis.
The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range, 0-50 with higher scores = greater tic severity).
The mean baseline YGTSS total tic score was 35.7. At 6 weeks, the reduction in total tic score was 8.9 with THC:CBD versus 2.5 with placebo.
A linear mixed-effects model (intention to treat) showed a significant interaction of treatment and visit number (P = .008), indicating a greater decrease (improvement) in tic score over time with THC:CBD, the study team reported.
On average, the magnitude of the tic reduction was “moderate” and comparable with the effect observed with existing treatments such as antipsychotic agents, the investigators noted.
The study was funded by the Wesley Medical Research Institute, Brisbane, and the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded research organization at the University of Sydney, Australia.
Dr. Mosley reported no relevant financial relationships.
A note from NORD
We extend our sincere thanks to busy health care professionals for taking time to engage with this issue, read the latest advances, and provide the best possible care for your patients. Your dedication is an inspiration, and we value the impact you make in the lives of others.
The year 2023 marks the 40th anniversary of the Orphan Drug Act (ODA), landmark legislation that incentivized drug companies to dedicate more resources towards the development of therapies for people with rare conditions. At the same time, we celebrate NORD’s 40th anniversary. The coalition of rare disease advocates who sparked rare disease advocacy and convinced lawmakers to pass the ODA in 1983 established NORD that same year to provide an ongoing, unified voice for the needs of the rare disease community. For 4 decades, NORD has worked tirelessly to drive supportive policies, advance medical research, and provide education and services for the now 30 million Americans with a rare disease, of which half are children.
In this issue of the Rare Neurological Disease Special Report, you will learn more about the history of the Orphan Drug Act and the founding of NORD. You will also find articles from rare disease specialists on specific diseases and some of the newest therapies approved under the ODA for conditions such as Friedreich ataxia, Fabry disease, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis. Also in the issue are articles about stiff person syndrome and Guillain-Barré syndrome and COVID vaccination.
We invite you to visit NORD’s webpage (www.rarediseases.org) to access resources for yourself and the patients and families you serve. NORD’s Continuing Medical Education Video Library offers cost-free, for-credit, on-demand rare disease courses developed in collaboration with Platform Q Health. NORD’s Caring for Rare quarterly newsletter provides updates on educational opportunities, events, and issues important for the rare disease community. NORD’s Rare Disease Database provides expert-reviewed reports on rare diseases in patient-friendly language.
As we celebrate the incredible progress made over the past 40 years, we also recognize that more than 95% of rare conditions still lack effective therapies. Continued research, development of new orphan products, and advances in treatment and care are needed. NORD will remain steadfast in its commitment to driving progress, inspiring innovation, and providing services for the rare community. We are deeply appreciative of the support you provide to people living with neurological conditions and encourage you to contact NORD any time we can be helpful to you.
Edward Neilan, MD, PhD
NORD’s Chief Medical Officer
We extend our sincere thanks to busy health care professionals for taking time to engage with this issue, read the latest advances, and provide the best possible care for your patients. Your dedication is an inspiration, and we value the impact you make in the lives of others.
The year 2023 marks the 40th anniversary of the Orphan Drug Act (ODA), landmark legislation that incentivized drug companies to dedicate more resources towards the development of therapies for people with rare conditions. At the same time, we celebrate NORD’s 40th anniversary. The coalition of rare disease advocates who sparked rare disease advocacy and convinced lawmakers to pass the ODA in 1983 established NORD that same year to provide an ongoing, unified voice for the needs of the rare disease community. For 4 decades, NORD has worked tirelessly to drive supportive policies, advance medical research, and provide education and services for the now 30 million Americans with a rare disease, of which half are children.
In this issue of the Rare Neurological Disease Special Report, you will learn more about the history of the Orphan Drug Act and the founding of NORD. You will also find articles from rare disease specialists on specific diseases and some of the newest therapies approved under the ODA for conditions such as Friedreich ataxia, Fabry disease, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis. Also in the issue are articles about stiff person syndrome and Guillain-Barré syndrome and COVID vaccination.
We invite you to visit NORD’s webpage (www.rarediseases.org) to access resources for yourself and the patients and families you serve. NORD’s Continuing Medical Education Video Library offers cost-free, for-credit, on-demand rare disease courses developed in collaboration with Platform Q Health. NORD’s Caring for Rare quarterly newsletter provides updates on educational opportunities, events, and issues important for the rare disease community. NORD’s Rare Disease Database provides expert-reviewed reports on rare diseases in patient-friendly language.
As we celebrate the incredible progress made over the past 40 years, we also recognize that more than 95% of rare conditions still lack effective therapies. Continued research, development of new orphan products, and advances in treatment and care are needed. NORD will remain steadfast in its commitment to driving progress, inspiring innovation, and providing services for the rare community. We are deeply appreciative of the support you provide to people living with neurological conditions and encourage you to contact NORD any time we can be helpful to you.
Edward Neilan, MD, PhD
NORD’s Chief Medical Officer
We extend our sincere thanks to busy health care professionals for taking time to engage with this issue, read the latest advances, and provide the best possible care for your patients. Your dedication is an inspiration, and we value the impact you make in the lives of others.
The year 2023 marks the 40th anniversary of the Orphan Drug Act (ODA), landmark legislation that incentivized drug companies to dedicate more resources towards the development of therapies for people with rare conditions. At the same time, we celebrate NORD’s 40th anniversary. The coalition of rare disease advocates who sparked rare disease advocacy and convinced lawmakers to pass the ODA in 1983 established NORD that same year to provide an ongoing, unified voice for the needs of the rare disease community. For 4 decades, NORD has worked tirelessly to drive supportive policies, advance medical research, and provide education and services for the now 30 million Americans with a rare disease, of which half are children.
In this issue of the Rare Neurological Disease Special Report, you will learn more about the history of the Orphan Drug Act and the founding of NORD. You will also find articles from rare disease specialists on specific diseases and some of the newest therapies approved under the ODA for conditions such as Friedreich ataxia, Fabry disease, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis. Also in the issue are articles about stiff person syndrome and Guillain-Barré syndrome and COVID vaccination.
We invite you to visit NORD’s webpage (www.rarediseases.org) to access resources for yourself and the patients and families you serve. NORD’s Continuing Medical Education Video Library offers cost-free, for-credit, on-demand rare disease courses developed in collaboration with Platform Q Health. NORD’s Caring for Rare quarterly newsletter provides updates on educational opportunities, events, and issues important for the rare disease community. NORD’s Rare Disease Database provides expert-reviewed reports on rare diseases in patient-friendly language.
As we celebrate the incredible progress made over the past 40 years, we also recognize that more than 95% of rare conditions still lack effective therapies. Continued research, development of new orphan products, and advances in treatment and care are needed. NORD will remain steadfast in its commitment to driving progress, inspiring innovation, and providing services for the rare community. We are deeply appreciative of the support you provide to people living with neurological conditions and encourage you to contact NORD any time we can be helpful to you.
Edward Neilan, MD, PhD
NORD’s Chief Medical Officer
Editor’s note
2023 is indeed a noteworthy year. As you will read in this issue, it marks the 40th anniversary of the landmark Orphan Drug Act and the formation of the National Organization for Rare Disorders (NORD). 2023 also marks the 30th anniversary of Neurology Reviews, the parent publication of the Rare Neurological Disease Special Report. While Neurology Reviews covers rare disease news throughout the year (see our Rare Disease Roundup in this issue), it is in our annual supplement where our rare disease news coverage and our partnership with NORD truly shines.
In this issue we take pride in taking a deeper look at some of the rare neurological diseases that have made headlines as well as the therapeutic advances and research breakthroughs that continue to benefit patients and the rare disease community as a whole. While I would prefer to humbly serve the rare disease community through our news coverage and educational efforts, I would be remiss if I didn’t mention that our 2022 Rare Neurological Disease Special Report won a Silver Regional Award in the category of annual supplement in the American Society of Business Publication Editors (Azbee) yearly competition. With that moment of bragging aside, I invite you to read this year’s issue, and I thank you for the success that this supplement has enjoyed since it launched in 2015.
Glenn S. Williams,
2023 is indeed a noteworthy year. As you will read in this issue, it marks the 40th anniversary of the landmark Orphan Drug Act and the formation of the National Organization for Rare Disorders (NORD). 2023 also marks the 30th anniversary of Neurology Reviews, the parent publication of the Rare Neurological Disease Special Report. While Neurology Reviews covers rare disease news throughout the year (see our Rare Disease Roundup in this issue), it is in our annual supplement where our rare disease news coverage and our partnership with NORD truly shines.
In this issue we take pride in taking a deeper look at some of the rare neurological diseases that have made headlines as well as the therapeutic advances and research breakthroughs that continue to benefit patients and the rare disease community as a whole. While I would prefer to humbly serve the rare disease community through our news coverage and educational efforts, I would be remiss if I didn’t mention that our 2022 Rare Neurological Disease Special Report won a Silver Regional Award in the category of annual supplement in the American Society of Business Publication Editors (Azbee) yearly competition. With that moment of bragging aside, I invite you to read this year’s issue, and I thank you for the success that this supplement has enjoyed since it launched in 2015.
Glenn S. Williams,
2023 is indeed a noteworthy year. As you will read in this issue, it marks the 40th anniversary of the landmark Orphan Drug Act and the formation of the National Organization for Rare Disorders (NORD). 2023 also marks the 30th anniversary of Neurology Reviews, the parent publication of the Rare Neurological Disease Special Report. While Neurology Reviews covers rare disease news throughout the year (see our Rare Disease Roundup in this issue), it is in our annual supplement where our rare disease news coverage and our partnership with NORD truly shines.
In this issue we take pride in taking a deeper look at some of the rare neurological diseases that have made headlines as well as the therapeutic advances and research breakthroughs that continue to benefit patients and the rare disease community as a whole. While I would prefer to humbly serve the rare disease community through our news coverage and educational efforts, I would be remiss if I didn’t mention that our 2022 Rare Neurological Disease Special Report won a Silver Regional Award in the category of annual supplement in the American Society of Business Publication Editors (Azbee) yearly competition. With that moment of bragging aside, I invite you to read this year’s issue, and I thank you for the success that this supplement has enjoyed since it launched in 2015.
Glenn S. Williams,
New guidelines for determining brain death released
The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.
As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.
But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.
Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.
“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”
The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
Four years in the making
Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.
A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.
The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.
The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.
In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
A uniform set of guidelines?
The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.
“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.
The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.
There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.
“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.
Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.
Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.
“But this attempts to unify things at the U.S. level, which is very important,” he said.
Permanent vs. irreversible
Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.
The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.
He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.
However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.
The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”
Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.
The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.
“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.
Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.
“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”
The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.
As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.
But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.
Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.
“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”
The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
Four years in the making
Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.
A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.
The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.
The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.
In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
A uniform set of guidelines?
The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.
“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.
The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.
There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.
“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.
Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.
Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.
“But this attempts to unify things at the U.S. level, which is very important,” he said.
Permanent vs. irreversible
Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.
The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.
He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.
However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.
The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”
Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.
The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.
“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.
Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.
“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”
The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.
As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.
But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.
Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.
“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”
The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
Four years in the making
Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.
A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.
The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.
The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.
In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
A uniform set of guidelines?
The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.
“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.
The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.
There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.
“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.
Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.
Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.
“But this attempts to unify things at the U.S. level, which is very important,” he said.
Permanent vs. irreversible
Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.
The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.
He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.
However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.
The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”
Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.
The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.
“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.
Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.
“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”
The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Are manual therapies effective at reducing chronic tension headache frequency in adults?
Evidence summary
Small studies offer mixed evidence of benefit
Seven RCTs using manual therapies to treat chronic tension headaches have reported the change in headache frequency (TABLE1-7). Most, but not all, manual therapies significantly improved headache frequency.
Participants ranged in age from 18 to 65 years, with mean age ranges of 33 to 42 years in each study. At baseline, patients had 10 or more tension-type headaches per month. The manual therapies varied in techniques, duration, and the training of the person performing the intervention:
- Twice-weekly chiropractic spinal manipulation for 6 weeks1
- Soft-tissue therapy plus spinal manipulation (8 treatments over 4 weeks)2
- Chiropractic spinal manipulation with or without amitriptyline for 14 weeks3
- Corrective osteopathic manipulation treatment (OMT) techniques tailored for each patient for 1 month4
- High-velocity low-amplitude manipulation (HVLA) plus exercise or myofascial release plus exercise twice weekly for 8 weeks5
- Manual therapy treatment consisting of a combination of mobilizations of the cervical and thoracic spine, exercises, and postural correction for up to 9 sessions of 30 minutes each6
- One hour of direct or indirect myofascial release treatment twice weekly for 12 weeks.7
Three studies involved chiropractic providers.1-3 One study (n = 19) found a positive effect, in which chiropractic manipulation augmented with amitriptyline performed better than chiropractic manipulation alone.3 Another chiropractic study did not find an immediate posttreatment benefit but did report significant headache reduction at the 4-week follow-up interval.1 The third chiropractic study did not show additional benefit from HVLA manipulation.2
One small study involving osteopathic physicians using OMT found reduced headache frequency after 12 weeks but not at 4 weeks.4 Another study, comparing HVLA or myofascial release with exercise to exercise alone, found benefit for the HVLA group but not for myofascial release; interventions in this study were performed by a physician with at least 6 years of unspecified manual therapy experience.5 A small study of manual therapists found improvement at the end of manual therapy but not at 18 months.6 Another small study using providers with 10 months’ experience with myofascial release found reduced headache frequency 4 weeks after a course of direct and indirect myofascial release (compared with sham release).7
Editor’s takeaway
It isn’t hard to imagine why muscle tension headaches might respond to certain forms of manual therapy. However, all available studies of these modalities have been small (< 100 patients) or lacked blinding, introducing the potential for significant bias. Nevertheless, for now it appears reasonable to refer interested patients with tension headache to an osteopathic physician for OMT or myofascial release to reduce headache frequency.
1. Boline PD, Kassak K, Bronfort G, et al. Spinal manipulation vs amitriptyline for the treatment of chronic tension-type headaches—a randomized clinical-trial. J Manipulative Physiol Ther. 1995;18:148-254.
2. Bove G. Spinal manipulation in the treatment of episodic tension-type headache: a randomized controlled trial. JAMA. 1998;280:1576-1579.
3. Vernon H, Jansz G, Goldsmith CH, et al. A randomized, placebo-controlled clinical trial of chiropractic and medical prophylactic treatment of adults with tension-type headache: results from a stopped trial. J Manipulative Physiol Ther. 2009;32:344-351.
4. Rolle G, Tremolizzo L, Somalvico F, et al. Pilot trial of osteopathic manipulative therapy for patients with frequent episodic tension-type headache. J Am Osteopath Assoc. 2014;114:678-685. doi: 10.7556/jaoa.2014.136
5. Corum M, Aydin T, Ceylan CM, et al. The comparative effects of spinal manipulation, myofascial release and exercise in tension-type headache patients with neck pain: a randomized controlled trial. Complement Ther Clin Pract. 2021;43:101319. doi: 0.1016/j.ctcp.2021.101319
6. Castien RF, van der Windt DAWM, Grooten A, et al. Effectiveness of manual therapy compared to usual care by the general practitioner for chronic tension-type headache: a pragmatic, randomised, clinical trial. Cephalalgia. 2009;31:133-143.
7. Ajimsha MS. Effectiveness of direct vs indirect technique myofascial release in the management of tension-type headache. J Bodyw Mov Ther. 2011;15:431-435. doi: 10.1016/j.jbmt.2011.01.021
Evidence summary
Small studies offer mixed evidence of benefit
Seven RCTs using manual therapies to treat chronic tension headaches have reported the change in headache frequency (TABLE1-7). Most, but not all, manual therapies significantly improved headache frequency.
Participants ranged in age from 18 to 65 years, with mean age ranges of 33 to 42 years in each study. At baseline, patients had 10 or more tension-type headaches per month. The manual therapies varied in techniques, duration, and the training of the person performing the intervention:
- Twice-weekly chiropractic spinal manipulation for 6 weeks1
- Soft-tissue therapy plus spinal manipulation (8 treatments over 4 weeks)2
- Chiropractic spinal manipulation with or without amitriptyline for 14 weeks3
- Corrective osteopathic manipulation treatment (OMT) techniques tailored for each patient for 1 month4
- High-velocity low-amplitude manipulation (HVLA) plus exercise or myofascial release plus exercise twice weekly for 8 weeks5
- Manual therapy treatment consisting of a combination of mobilizations of the cervical and thoracic spine, exercises, and postural correction for up to 9 sessions of 30 minutes each6
- One hour of direct or indirect myofascial release treatment twice weekly for 12 weeks.7
Three studies involved chiropractic providers.1-3 One study (n = 19) found a positive effect, in which chiropractic manipulation augmented with amitriptyline performed better than chiropractic manipulation alone.3 Another chiropractic study did not find an immediate posttreatment benefit but did report significant headache reduction at the 4-week follow-up interval.1 The third chiropractic study did not show additional benefit from HVLA manipulation.2
One small study involving osteopathic physicians using OMT found reduced headache frequency after 12 weeks but not at 4 weeks.4 Another study, comparing HVLA or myofascial release with exercise to exercise alone, found benefit for the HVLA group but not for myofascial release; interventions in this study were performed by a physician with at least 6 years of unspecified manual therapy experience.5 A small study of manual therapists found improvement at the end of manual therapy but not at 18 months.6 Another small study using providers with 10 months’ experience with myofascial release found reduced headache frequency 4 weeks after a course of direct and indirect myofascial release (compared with sham release).7
Editor’s takeaway
It isn’t hard to imagine why muscle tension headaches might respond to certain forms of manual therapy. However, all available studies of these modalities have been small (< 100 patients) or lacked blinding, introducing the potential for significant bias. Nevertheless, for now it appears reasonable to refer interested patients with tension headache to an osteopathic physician for OMT or myofascial release to reduce headache frequency.
Evidence summary
Small studies offer mixed evidence of benefit
Seven RCTs using manual therapies to treat chronic tension headaches have reported the change in headache frequency (TABLE1-7). Most, but not all, manual therapies significantly improved headache frequency.
Participants ranged in age from 18 to 65 years, with mean age ranges of 33 to 42 years in each study. At baseline, patients had 10 or more tension-type headaches per month. The manual therapies varied in techniques, duration, and the training of the person performing the intervention:
- Twice-weekly chiropractic spinal manipulation for 6 weeks1
- Soft-tissue therapy plus spinal manipulation (8 treatments over 4 weeks)2
- Chiropractic spinal manipulation with or without amitriptyline for 14 weeks3
- Corrective osteopathic manipulation treatment (OMT) techniques tailored for each patient for 1 month4
- High-velocity low-amplitude manipulation (HVLA) plus exercise or myofascial release plus exercise twice weekly for 8 weeks5
- Manual therapy treatment consisting of a combination of mobilizations of the cervical and thoracic spine, exercises, and postural correction for up to 9 sessions of 30 minutes each6
- One hour of direct or indirect myofascial release treatment twice weekly for 12 weeks.7
Three studies involved chiropractic providers.1-3 One study (n = 19) found a positive effect, in which chiropractic manipulation augmented with amitriptyline performed better than chiropractic manipulation alone.3 Another chiropractic study did not find an immediate posttreatment benefit but did report significant headache reduction at the 4-week follow-up interval.1 The third chiropractic study did not show additional benefit from HVLA manipulation.2
One small study involving osteopathic physicians using OMT found reduced headache frequency after 12 weeks but not at 4 weeks.4 Another study, comparing HVLA or myofascial release with exercise to exercise alone, found benefit for the HVLA group but not for myofascial release; interventions in this study were performed by a physician with at least 6 years of unspecified manual therapy experience.5 A small study of manual therapists found improvement at the end of manual therapy but not at 18 months.6 Another small study using providers with 10 months’ experience with myofascial release found reduced headache frequency 4 weeks after a course of direct and indirect myofascial release (compared with sham release).7
Editor’s takeaway
It isn’t hard to imagine why muscle tension headaches might respond to certain forms of manual therapy. However, all available studies of these modalities have been small (< 100 patients) or lacked blinding, introducing the potential for significant bias. Nevertheless, for now it appears reasonable to refer interested patients with tension headache to an osteopathic physician for OMT or myofascial release to reduce headache frequency.
1. Boline PD, Kassak K, Bronfort G, et al. Spinal manipulation vs amitriptyline for the treatment of chronic tension-type headaches—a randomized clinical-trial. J Manipulative Physiol Ther. 1995;18:148-254.
2. Bove G. Spinal manipulation in the treatment of episodic tension-type headache: a randomized controlled trial. JAMA. 1998;280:1576-1579.
3. Vernon H, Jansz G, Goldsmith CH, et al. A randomized, placebo-controlled clinical trial of chiropractic and medical prophylactic treatment of adults with tension-type headache: results from a stopped trial. J Manipulative Physiol Ther. 2009;32:344-351.
4. Rolle G, Tremolizzo L, Somalvico F, et al. Pilot trial of osteopathic manipulative therapy for patients with frequent episodic tension-type headache. J Am Osteopath Assoc. 2014;114:678-685. doi: 10.7556/jaoa.2014.136
5. Corum M, Aydin T, Ceylan CM, et al. The comparative effects of spinal manipulation, myofascial release and exercise in tension-type headache patients with neck pain: a randomized controlled trial. Complement Ther Clin Pract. 2021;43:101319. doi: 0.1016/j.ctcp.2021.101319
6. Castien RF, van der Windt DAWM, Grooten A, et al. Effectiveness of manual therapy compared to usual care by the general practitioner for chronic tension-type headache: a pragmatic, randomised, clinical trial. Cephalalgia. 2009;31:133-143.
7. Ajimsha MS. Effectiveness of direct vs indirect technique myofascial release in the management of tension-type headache. J Bodyw Mov Ther. 2011;15:431-435. doi: 10.1016/j.jbmt.2011.01.021
1. Boline PD, Kassak K, Bronfort G, et al. Spinal manipulation vs amitriptyline for the treatment of chronic tension-type headaches—a randomized clinical-trial. J Manipulative Physiol Ther. 1995;18:148-254.
2. Bove G. Spinal manipulation in the treatment of episodic tension-type headache: a randomized controlled trial. JAMA. 1998;280:1576-1579.
3. Vernon H, Jansz G, Goldsmith CH, et al. A randomized, placebo-controlled clinical trial of chiropractic and medical prophylactic treatment of adults with tension-type headache: results from a stopped trial. J Manipulative Physiol Ther. 2009;32:344-351.
4. Rolle G, Tremolizzo L, Somalvico F, et al. Pilot trial of osteopathic manipulative therapy for patients with frequent episodic tension-type headache. J Am Osteopath Assoc. 2014;114:678-685. doi: 10.7556/jaoa.2014.136
5. Corum M, Aydin T, Ceylan CM, et al. The comparative effects of spinal manipulation, myofascial release and exercise in tension-type headache patients with neck pain: a randomized controlled trial. Complement Ther Clin Pract. 2021;43:101319. doi: 0.1016/j.ctcp.2021.101319
6. Castien RF, van der Windt DAWM, Grooten A, et al. Effectiveness of manual therapy compared to usual care by the general practitioner for chronic tension-type headache: a pragmatic, randomised, clinical trial. Cephalalgia. 2009;31:133-143.
7. Ajimsha MS. Effectiveness of direct vs indirect technique myofascial release in the management of tension-type headache. J Bodyw Mov Ther. 2011;15:431-435. doi: 10.1016/j.jbmt.2011.01.021
EVIDENCE-BASED ANSWER:
MAYBE. Among patients with chronic tension headaches, manual therapies may reduce headache frequency more than sham manual therapy, usual care, or exercise treatments—by 1.5 to 4.2 headaches or days with headache per week (strength of recommendation, B; preponderance of evidence from primarily small, heterogeneous randomized controlled trials [RCTs]).
Not acne, but what?
AN OTHERWISE HEALTHY
Scattered papules and pustules were present on the forehead, nose, and cheeks, with background erythema and telangiectasias (FIGURE 1). A few pinpoint crusted excoriations were noted. A sample was taken from the papules and pustules using a #15 blade and submitted for examination.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Rosacea with Demodex mites
Under light microscopy, the scraping revealed Demodex mites (FIGURE 2). It has been proposed that these mites play a role in the inflammatory process seen in rosacea, although studies have yet to determine whether the inflammatory symptoms of rosacea cause the mites to proliferate or if the mites contribute to the initial inflammatory process.1,2
Demodex folliculorum and D brevis are part of normal skin flora; they are found in about 12% of all follicles and most commonly involve the face.3 They often become abundant in the presence of numerous sebaceous glands. Men have more sebaceous glands than women do, and thus run a greater risk for infestation with mites. An abnormal proliferation of Demodex mites can lead to demodicosis.
Demodex mites can be examined microscopically via the skin surface sampling technique known as scraping, which was done in this case. Samples taken from the papules and pustules utilizing a #15 blade are placed in immersion oil on a glass slide, cover-slipped, and examined by light microscopy.
Rosacea is thought to be an inflammatory disease in which the immune system is triggered by a variety of factors, including UV light, heat, stress, alcohol, hormonal influences, and microorganisms.1,4 The disease is found in up to 10% of the population worldwide.1
The diagnosis of rosacea requires at least 1 of the 2 “core features”—persistent central facial erythema or phymatous changes—or 2 of 4 “major features”: papules/pustules, ocular manifestation, flushing, and telangiectasias. There are 3 phenotypes: ocular, papulopustular, and erythematotelangiectatic.5,6
Continue to: The connection
The connection. Papulopustular and erythematotelangiectatic rosacea may be caused by a proliferation of Demodex mites and increased vascular endothelial growth factor production.2 In fact, a proliferation of Demodex is seen in almost all cases of papulopustular rosacea and more than 60% of cases of erythematotelangiectatic rosacea.2
Patient age and distribution of lesions narrowed the differential
Acne vulgaris is an inflammatory disease of the pilosebaceous units caused by increased sebum production, inflammation, and bacterial colonization (Propionibacterium acnes) of hair follicles on the face, neck, chest, and other areas. Both inflammatory and noninflammatory lesions can be present, and in serious cases, scarring can result.7 The case patient’s age and accompanying broad erythema were more consistent with rosacea than acne vulgaris.
Seborrheic dermatitis is a common skin condition usually stemming from an inflammatory reaction to a common yeast. Classic symptoms include scaling and erythema of the scalp and central face, as well as pruritus. Topical antifungals such as ketoconazole 2% cream and 2% shampoo are the mainstay of treatment.8 The broad distribution and papulopustules in this patient argue against the diagnosis of seborrheic dermatitis.
Systemic lupus erythematosus is a systemic inflammatory disease that often has cutaneous manifestations. Acute lupus manifests as an erythematous “butterfly rash” across the face and cheeks. Chronic discoid lupus involves depigmented plaques, erythematous macules, telangiectasias, and scarring with loss of normal hair follicles. These findings classically are photodistributed.9 The classic broad erythema extending from the cheeks over the bridge of the nose was not present in this patient.
Treatment is primarily topical
Mild cases of rosacea often can be managed with topical antibiotic creams. More severe cases may require systemic antibiotics such as tetracycline or doxycycline, although these are used with caution due to the potential for antibiotic resistance.
Ivermectin 1% cream is a US Food and Drug Administration–approved medication that is applied once daily for up to a year to treat the inflammatory pustules associated with Demodex mites. Although it is costly, studies have shown better results with topical ivermectin than with other topical medications (eg, metronidazole 0.75% gel or cream). However, metronidazole 0.75% gel applied twice daily and oral tetracycline 250 mg or doxycycline 100 mg daily or twice daily for at least 2 months often are utilized when the cost of topical ivermectin is prohibitive.10
Our patient was treated with a combination of doxycycline 100 mg daily for 30 days and
1. Forton FMN. Rosacea, an infectious disease: why rosacea with papulopustules should be considered a demodicosis. A narrative review. J Eur Acad Dermatol Venereol. 2022;36:987-1002. doi: 10.1111/jdv.18049
2. Forton FMN. The pathogenic role of demodex mites in rosacea: a potential therapeutic target already in erythematotelangiectatic rosacea? Dermatol Ther (Heidelb). 2020;10:1229-1253. doi: 10.1007/s13555-020-00458-9
3. Elston DM. Demodex mites: facts and controversies. Clin Dermatol. 2010;28:502-504. doi: 10.1016/j.clindermatol.2010.03.006
4. Erbağci Z, OzgöztaŞi O. The significance of demodex folliculorum density in rosacea. Int J Dermatol. 1998;37:421-425. doi: 10.1046/j.1365-4362.1998.00218.x
5. Tan J, Almeida LMC, Criber B, et al. Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2017;176:431-438. doi: 10.1111/bjd.15122
6. Gallo RL, Granstein RD, Kang S, et al. Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78:148-155. doi: 10.1016/j.jaad.2017.08.037
7. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012;379:361-372. doi: 10.1016/S0140-6736(11)60321-8.
8. Clark GW, Pope SM, Jaboori KA. Diagnosis and treatment of seborrheic dermatitis. Am Fam Physician. 2015;91:185-190.
9. Yell JA, Mbuagbaw J, Burge SM. Cutaneous manifestations of systemic lupus erythematosus. Br J Dermatol. 1996;135:355-362.
10. Raedler LA. Soolantra (ivermectin) 1% cream: a novel, antibiotic-free agent approved for the treatment of patients with rosacea. Am Health Drug Benefits. 2015;8(Spec Feature):122-125.
AN OTHERWISE HEALTHY
Scattered papules and pustules were present on the forehead, nose, and cheeks, with background erythema and telangiectasias (FIGURE 1). A few pinpoint crusted excoriations were noted. A sample was taken from the papules and pustules using a #15 blade and submitted for examination.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Rosacea with Demodex mites
Under light microscopy, the scraping revealed Demodex mites (FIGURE 2). It has been proposed that these mites play a role in the inflammatory process seen in rosacea, although studies have yet to determine whether the inflammatory symptoms of rosacea cause the mites to proliferate or if the mites contribute to the initial inflammatory process.1,2
Demodex folliculorum and D brevis are part of normal skin flora; they are found in about 12% of all follicles and most commonly involve the face.3 They often become abundant in the presence of numerous sebaceous glands. Men have more sebaceous glands than women do, and thus run a greater risk for infestation with mites. An abnormal proliferation of Demodex mites can lead to demodicosis.
Demodex mites can be examined microscopically via the skin surface sampling technique known as scraping, which was done in this case. Samples taken from the papules and pustules utilizing a #15 blade are placed in immersion oil on a glass slide, cover-slipped, and examined by light microscopy.
Rosacea is thought to be an inflammatory disease in which the immune system is triggered by a variety of factors, including UV light, heat, stress, alcohol, hormonal influences, and microorganisms.1,4 The disease is found in up to 10% of the population worldwide.1
The diagnosis of rosacea requires at least 1 of the 2 “core features”—persistent central facial erythema or phymatous changes—or 2 of 4 “major features”: papules/pustules, ocular manifestation, flushing, and telangiectasias. There are 3 phenotypes: ocular, papulopustular, and erythematotelangiectatic.5,6
Continue to: The connection
The connection. Papulopustular and erythematotelangiectatic rosacea may be caused by a proliferation of Demodex mites and increased vascular endothelial growth factor production.2 In fact, a proliferation of Demodex is seen in almost all cases of papulopustular rosacea and more than 60% of cases of erythematotelangiectatic rosacea.2
Patient age and distribution of lesions narrowed the differential
Acne vulgaris is an inflammatory disease of the pilosebaceous units caused by increased sebum production, inflammation, and bacterial colonization (Propionibacterium acnes) of hair follicles on the face, neck, chest, and other areas. Both inflammatory and noninflammatory lesions can be present, and in serious cases, scarring can result.7 The case patient’s age and accompanying broad erythema were more consistent with rosacea than acne vulgaris.
Seborrheic dermatitis is a common skin condition usually stemming from an inflammatory reaction to a common yeast. Classic symptoms include scaling and erythema of the scalp and central face, as well as pruritus. Topical antifungals such as ketoconazole 2% cream and 2% shampoo are the mainstay of treatment.8 The broad distribution and papulopustules in this patient argue against the diagnosis of seborrheic dermatitis.
Systemic lupus erythematosus is a systemic inflammatory disease that often has cutaneous manifestations. Acute lupus manifests as an erythematous “butterfly rash” across the face and cheeks. Chronic discoid lupus involves depigmented plaques, erythematous macules, telangiectasias, and scarring with loss of normal hair follicles. These findings classically are photodistributed.9 The classic broad erythema extending from the cheeks over the bridge of the nose was not present in this patient.
Treatment is primarily topical
Mild cases of rosacea often can be managed with topical antibiotic creams. More severe cases may require systemic antibiotics such as tetracycline or doxycycline, although these are used with caution due to the potential for antibiotic resistance.
Ivermectin 1% cream is a US Food and Drug Administration–approved medication that is applied once daily for up to a year to treat the inflammatory pustules associated with Demodex mites. Although it is costly, studies have shown better results with topical ivermectin than with other topical medications (eg, metronidazole 0.75% gel or cream). However, metronidazole 0.75% gel applied twice daily and oral tetracycline 250 mg or doxycycline 100 mg daily or twice daily for at least 2 months often are utilized when the cost of topical ivermectin is prohibitive.10
Our patient was treated with a combination of doxycycline 100 mg daily for 30 days and
AN OTHERWISE HEALTHY
Scattered papules and pustules were present on the forehead, nose, and cheeks, with background erythema and telangiectasias (FIGURE 1). A few pinpoint crusted excoriations were noted. A sample was taken from the papules and pustules using a #15 blade and submitted for examination.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Rosacea with Demodex mites
Under light microscopy, the scraping revealed Demodex mites (FIGURE 2). It has been proposed that these mites play a role in the inflammatory process seen in rosacea, although studies have yet to determine whether the inflammatory symptoms of rosacea cause the mites to proliferate or if the mites contribute to the initial inflammatory process.1,2
Demodex folliculorum and D brevis are part of normal skin flora; they are found in about 12% of all follicles and most commonly involve the face.3 They often become abundant in the presence of numerous sebaceous glands. Men have more sebaceous glands than women do, and thus run a greater risk for infestation with mites. An abnormal proliferation of Demodex mites can lead to demodicosis.
Demodex mites can be examined microscopically via the skin surface sampling technique known as scraping, which was done in this case. Samples taken from the papules and pustules utilizing a #15 blade are placed in immersion oil on a glass slide, cover-slipped, and examined by light microscopy.
Rosacea is thought to be an inflammatory disease in which the immune system is triggered by a variety of factors, including UV light, heat, stress, alcohol, hormonal influences, and microorganisms.1,4 The disease is found in up to 10% of the population worldwide.1
The diagnosis of rosacea requires at least 1 of the 2 “core features”—persistent central facial erythema or phymatous changes—or 2 of 4 “major features”: papules/pustules, ocular manifestation, flushing, and telangiectasias. There are 3 phenotypes: ocular, papulopustular, and erythematotelangiectatic.5,6
Continue to: The connection
The connection. Papulopustular and erythematotelangiectatic rosacea may be caused by a proliferation of Demodex mites and increased vascular endothelial growth factor production.2 In fact, a proliferation of Demodex is seen in almost all cases of papulopustular rosacea and more than 60% of cases of erythematotelangiectatic rosacea.2
Patient age and distribution of lesions narrowed the differential
Acne vulgaris is an inflammatory disease of the pilosebaceous units caused by increased sebum production, inflammation, and bacterial colonization (Propionibacterium acnes) of hair follicles on the face, neck, chest, and other areas. Both inflammatory and noninflammatory lesions can be present, and in serious cases, scarring can result.7 The case patient’s age and accompanying broad erythema were more consistent with rosacea than acne vulgaris.
Seborrheic dermatitis is a common skin condition usually stemming from an inflammatory reaction to a common yeast. Classic symptoms include scaling and erythema of the scalp and central face, as well as pruritus. Topical antifungals such as ketoconazole 2% cream and 2% shampoo are the mainstay of treatment.8 The broad distribution and papulopustules in this patient argue against the diagnosis of seborrheic dermatitis.
Systemic lupus erythematosus is a systemic inflammatory disease that often has cutaneous manifestations. Acute lupus manifests as an erythematous “butterfly rash” across the face and cheeks. Chronic discoid lupus involves depigmented plaques, erythematous macules, telangiectasias, and scarring with loss of normal hair follicles. These findings classically are photodistributed.9 The classic broad erythema extending from the cheeks over the bridge of the nose was not present in this patient.
Treatment is primarily topical
Mild cases of rosacea often can be managed with topical antibiotic creams. More severe cases may require systemic antibiotics such as tetracycline or doxycycline, although these are used with caution due to the potential for antibiotic resistance.
Ivermectin 1% cream is a US Food and Drug Administration–approved medication that is applied once daily for up to a year to treat the inflammatory pustules associated with Demodex mites. Although it is costly, studies have shown better results with topical ivermectin than with other topical medications (eg, metronidazole 0.75% gel or cream). However, metronidazole 0.75% gel applied twice daily and oral tetracycline 250 mg or doxycycline 100 mg daily or twice daily for at least 2 months often are utilized when the cost of topical ivermectin is prohibitive.10
Our patient was treated with a combination of doxycycline 100 mg daily for 30 days and
1. Forton FMN. Rosacea, an infectious disease: why rosacea with papulopustules should be considered a demodicosis. A narrative review. J Eur Acad Dermatol Venereol. 2022;36:987-1002. doi: 10.1111/jdv.18049
2. Forton FMN. The pathogenic role of demodex mites in rosacea: a potential therapeutic target already in erythematotelangiectatic rosacea? Dermatol Ther (Heidelb). 2020;10:1229-1253. doi: 10.1007/s13555-020-00458-9
3. Elston DM. Demodex mites: facts and controversies. Clin Dermatol. 2010;28:502-504. doi: 10.1016/j.clindermatol.2010.03.006
4. Erbağci Z, OzgöztaŞi O. The significance of demodex folliculorum density in rosacea. Int J Dermatol. 1998;37:421-425. doi: 10.1046/j.1365-4362.1998.00218.x
5. Tan J, Almeida LMC, Criber B, et al. Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2017;176:431-438. doi: 10.1111/bjd.15122
6. Gallo RL, Granstein RD, Kang S, et al. Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78:148-155. doi: 10.1016/j.jaad.2017.08.037
7. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012;379:361-372. doi: 10.1016/S0140-6736(11)60321-8.
8. Clark GW, Pope SM, Jaboori KA. Diagnosis and treatment of seborrheic dermatitis. Am Fam Physician. 2015;91:185-190.
9. Yell JA, Mbuagbaw J, Burge SM. Cutaneous manifestations of systemic lupus erythematosus. Br J Dermatol. 1996;135:355-362.
10. Raedler LA. Soolantra (ivermectin) 1% cream: a novel, antibiotic-free agent approved for the treatment of patients with rosacea. Am Health Drug Benefits. 2015;8(Spec Feature):122-125.
1. Forton FMN. Rosacea, an infectious disease: why rosacea with papulopustules should be considered a demodicosis. A narrative review. J Eur Acad Dermatol Venereol. 2022;36:987-1002. doi: 10.1111/jdv.18049
2. Forton FMN. The pathogenic role of demodex mites in rosacea: a potential therapeutic target already in erythematotelangiectatic rosacea? Dermatol Ther (Heidelb). 2020;10:1229-1253. doi: 10.1007/s13555-020-00458-9
3. Elston DM. Demodex mites: facts and controversies. Clin Dermatol. 2010;28:502-504. doi: 10.1016/j.clindermatol.2010.03.006
4. Erbağci Z, OzgöztaŞi O. The significance of demodex folliculorum density in rosacea. Int J Dermatol. 1998;37:421-425. doi: 10.1046/j.1365-4362.1998.00218.x
5. Tan J, Almeida LMC, Criber B, et al. Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2017;176:431-438. doi: 10.1111/bjd.15122
6. Gallo RL, Granstein RD, Kang S, et al. Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78:148-155. doi: 10.1016/j.jaad.2017.08.037
7. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012;379:361-372. doi: 10.1016/S0140-6736(11)60321-8.
8. Clark GW, Pope SM, Jaboori KA. Diagnosis and treatment of seborrheic dermatitis. Am Fam Physician. 2015;91:185-190.
9. Yell JA, Mbuagbaw J, Burge SM. Cutaneous manifestations of systemic lupus erythematosus. Br J Dermatol. 1996;135:355-362.
10. Raedler LA. Soolantra (ivermectin) 1% cream: a novel, antibiotic-free agent approved for the treatment of patients with rosacea. Am Health Drug Benefits. 2015;8(Spec Feature):122-125.
How best to diagnose and manage abdominal aortic aneurysms
Ruptured abdominal aortic aneurysms (AAAs) caused about 6000 deaths annually in the United States between 2014 and 20201 and are associated with a pooled mortality rate of 81%.2 They result from a distinct degenerative process of the layers of the aortic wall.2 An AAA is defined as an abdominal aorta whose dilation is > 50% normal (more commonly, a diameter > 3 cm).3,4 The risk for rupture correlates closely with size; most ruptures occur in aneurysms > 5.5 cm3,4 (TABLE 15).
Most AAAs are asymptomatic and often go undetected until rupture, resulting in poor outcomes. Because of a low and declining prevalence of AAA and ruptured AAA in developed countries, screening recommendations target high-risk groups rather than the general population.4,6-8 This review summarizes risk factors, prevalence, and current evidence-based screening and management recommendations for AAA.
Who’s at risk?
Age is the most significant nonmodifiable risk factor, with AAA rupture uncommon in patients younger than 55 years.9 One retrospective study found the odds ratio (OR) for diagnosing AAA was 9.41 in adults ages 65 to 69 years (95% CI, 8.76-10.12; P < .0001) and 14.46 (95% CI, 13.45-15.55; P < .0001) in adults ages 70 to 74 years, compared to adults younger than 55 years.10
Smoking is the most potent modifiable risk factor for AAA. Among patients with AAA, > 90% have a history of smoking.4 The association between smoking and AAA is dose dependent, with an OR of 2.61 (95% CI, 2.47-2.74) in patients with a pack-per-year history < 5 years and 12.13 (95% CI, 11.66-12.61) in patients with a pack-per-year history > 35 years, compared to nonsmokers.10 The risk for AAA increases with smoking duration but decreases with cessation duration.4,10 Smoking cessation remains an important intervention, as active smokers have higher AAA rupture rates.11
Other risk factors for AAA include concomitant cardiovascular disease (CVD) such as coronary artery disease (CAD), cerebrovascular disease, atherosclerosis, dyslipidemia, and hypertension.10 Factors associated with reduced risk for AAA include African American race, Hispanic ethnicity, Asian ethnicity, diabetes, smoking cessation, consuming fruits and vegetables > 3 times per week, and exercising more than once per week.6,10
Prevalence declines but sex-based disparities in outcomes persist
The prevalence of AAA has declined in the United States and Europe in recent decades, correlating with declining rates of smoking.4,12 Reports published between 2011 and 2019 estimate that AAA prevalence in men older than 60 years has declined over time, with a prevalence of 1.2% to 3.3%.6 The prevalence of AAA has also decreased in women,6,13,14 estimated in 1 study to be as low as 0.74%.13 Similarly, deaths from ruptured AAA have declined markedly in the United States—by 70% between 1999 and 2016 according to 1 analysis.9
One striking difference in the male-female data is that although AAAs are more common in men, there is a 2- to 4-fold higher risk for rupture in women, who account for nearly half of all AAA-related deaths.9,10,15-17 The reasons for this heightened risk to women despite lower prevalence are not fully understood but are likely multifactorial and related to a general lack of screening for AAA in women, tendency for AAA to rupture at smaller diameters in women, rupture at an older age in women, and a history of worse surgical outcomes in women than men (though the gap in surgical outcomes appears to be closing).9,10,18
Continue to: While declines in AAA and AAA-related...
While declines in AAA and AAA-related death are largely attributed to lower smoking rates, other likely contributing factors include the implementation of screening programs, incidental detection during cross-sectional imaging, and improved surgical techniques and management of CV risk factors (eg, hypertension, hyperlipidemia).9,10
The benefits of screening older men
Randomized controlled trials (RCTs) have demonstrated the benefits of AAA screening programs. A meta-analysis of 4 populationbased RCTs of AAA screening in men ≥ 65 years demonstrated statistically significant reductions in AAA rupture (OR = 0.62; 95% CI, 0.55-0.70) and death from AAA (OR = 0.65; 95% CI, 0.57-0.74) over 12 to 15 years, with a number needed to screen (NNS) of 305 (95% CI, 248-411) to prevent 1 AAA-related death.18 The study also found screening decreases the rate of emergent surgeries for AAA (OR = 0.57; 95% CI, 0.48-0.68) while increasing the number of elective surgeries (OR = 1.44; 95% CI, 1.34-1.55) over 4 to 15 years.18
Only 1 study has demonstrated an improvement in all-cause mortality with screening programs, with a relatively small benefit (OR = 0.97; 95% CI, 0.94-0.99).19 Only 1 of the studies included women and, while underpowered, showed no difference in AAA-related death or rupture.20 Guidelines and recommendations of various countries and professional societies focus screening on subgroups at highest risk for AAA.4,6-8,18
Screening recommendations from USPSTF and others
The US Preventive Services Task Force (USPSTF) currently recommends one-time ultrasound screening for AAA in men ages 65 to 75 years who have ever smoked (commonly defined as having smoked > 100 cigarettes) in their lifetime.6 This grade “B” recommendation, initially made in 2005 and reaffirmed in the 2014 and 2019 USPSTF updates, recommends screening the highest-risk segment of the population (ie, older male smokers).
In men ages 65 to 75 years with no smoking history, rather than routine screening, the USPSTF recommends selectively offering screening based on the patient’s medical history, family history, risk factors, and personal values (with a “C” grade).6 The USPSTF continues to recommend against screening for AAA in women with no smoking history and no family history of AAA.6 According to the USPSTF, the evidence is insufficient to recommend for or against screening women ages 65 to 75 years who have ever smoked or have a family history of AAA (“I” statement).6
Continue to: One critique of the USPSTF recommendations
One critique of the USPSTF recommendations is that they fail to detect a significant portion of patients with AAA and AAA rupture. For example, in a retrospective analysis of 55,197 patients undergoing AAA repair, only 33% would have been detected by the USPSTF grade “B” recommendation to screen male smokers ages 65 to 75 years, and an analysis of AAA-related fatalities found 43% would be missed by USPSTF criteria.9,21
Screening guidelines from the Society for Vascular Surgery (SVS) are broader than those of the USPSTF, in an attempt to capture a larger percentage of the population at risk for AAA-related disease by extrapolating from epidemiologic data. The SVS guidelines include screening for women ages 65 to 75 years with a smoking history, screening men and women ages 65 to 75 years who have a first-degree relative with AAA, and consideration of screening patients older than 75 years if they are in good health and have a first-degree relative with AAA or a smoking history and have not been previously screened.4 However, these expanded recommendations are not supported by patient-oriented evidence.6
Attempts to broaden screening guidelines must be tempered by potential risks for harm, primarily overdiagnosis (ie, diagnosing AAAs that would not otherwise rise to clinical significance) and overtreatment (ie, resulting in unnecessary imaging, appointments, anxiety, or surgery). Negative psychological effects on quality of life after a diagnosis of AAA have not been shown to cause significant harm.6,18
A recent UK analysis found that screening programs for AAA in women modeled after those in men are not cost effective, with an NNS to prevent 1 death of 3900 in women vs 700 in men.15,18 Another recent trial of ultrasound screening in 5200 high-risk women ages 65 to 74 years found an AAA incidence of 0.29% (95% CI, 0.18%-0.48%) in which only 3 large aneurysms were identified.22
In the United States, rates of screening for AAA remain low.23 One study has shown electronic medical record–based reminders increased screening rates from 48% to 80%.24 Point-of-care bedside ultrasound performed by clinicians also could improve screening rates. Multiple studies have demonstrated that screening and diagnosis of AAA can be performed safely and effectively at the bedside by nonradiologists such as family physicians and emergency physicians.25-28 In 1 study, such exams added < 4 minutes to the patient encounter.26 Follow-up surveillance schedules for those identified as having a AAA are summarized in TABLE 2.4
Continue to: Management options
Management options: Immediate repair or surveillance?
After diagnosing AAA, important decisions must be made regarding management, including indications for surgical repair, appropriate follow-up surveillance, and medications for secondary prevention and cardiovascular risk reduction.
EVAR vs open repair
The 2 main surgical strategies for aneurysm repair are open repair and endovascular repair (EVAR). In the United States, EVAR is becoming the more common approach and was used to repair asymptomatic aneurysms in > 80% of patients and ruptured aneurysms in 50% of patients.6 There have been multiple RCTs assessing EVAR and open repair for large and small aneurysms.29-34 Findings across these studies consistently show EVAR is associated with lower immediate (ie, 30-day) morbidity and mortality but no longer-term survival benefit compared to open repair.
EVAR procedures require ongoing long-term surveillance for endovascular leakage and other complications, resulting in an increased need for re-intervention.31,33,35 For these reasons, the National Institute for Health and Care Excellence (NICE) guidelines suggest open repair as the preferred modality.7 However, SVS and the American College of Cardiology Foundation/American Heart Association guidance support either EVAR or open repair, noting that open repair may be preferable in patients unable to engage in long-term follow-up surveillance.36
Indications for repair. In general, repair is indicated when an aneurysm reaches or exceeds 5.5 cm.4,7 Both SVS and NICE also recommend clinicians consider surgical repair of smaller, rapidly expanding aneurysms (> 1 cm over a 1-year period).4,7 Based on evidence suggesting a higher risk for rupture in women with smaller aneurysms,14,37 SVS recommends clinicians consider surgical repair in women with an AAA ≥ 5.0 cm. Several RCTs evaluating the benefits of immediate repair for smaller-sized aneurysms (4.0-5.5 cm) favored surveillance.38,39 Accepted indications for surgical repair are summarized in TABLE 3.4,7,34Surgical repair recommendations also are based on aneurysm morphology, which can be fusiform or saccular (FIGURE). More than 90% of AAAs are fusiform.40 Although saccular AAAs are less common, some studies suggest they are more prone to rupture than fusiform AAAs, and SVS guidelines suggest surgical repair of saccular aneurysms regardless of size.4,41,42
Perioperative and long-term risks. Both EVAR and open repair of AAA carry a high perioperative and long-term risk for death, as patients often have multiple comorbidities. A 2019 trial comparing EVAR to open repair with 14 years of follow-up reported death in 68% of patients in the EVAR group and 70% in the open repair group. 31 Among these deaths, 2.7% in the EVAR group and 3.7% in the open repair group were aneurysm related.31 The study also found a second surgical intervention was required in 19.8% of patients in the open repair group and 26.7% in the EVAR group.31
Continue to: When assessing perioperative risk...
When assessing perioperative risk, SVS guidelines recommend clinicians employ a shared decision-making approach with patients that incorporates Vascular Quality Initiative (VQI) mortality risk score.4 (VQI risk calculators are available at https://qxmd.com/vascular-study-group-new-england-decision-support-tools.43)
Medication management
Based on the close association of aortic aneurysm with atherosclerotic CVD (ASCVD), professional societies such as the European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) have suggested aortic aneurysm is equivalent to ASCVD and should be managed medically in a similar manner to peripheral arterial disease.44 Indeed, many patients with AAA may have concomitant CAD or other arterial vascular diseases (eg, carotid, lower extremity).
Statins. In its guidelines, the ESC/EAS consider patients with AAA at “very high risk” for adverse CV events and suggest pharmacotherapy with high-intensity statins, adding ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors if needed, to reduce low-density lipoprotein cholesterol ≥ 50% from baseline, with a goal of < 55 mg/dL.44 Statin therapy additionally lowers all-cause postoperative mortality in patients undergoing AAA repair but does not affect the rate of aneurysm expansion.45
Aspirin and other anticoagulants. Although aspirin therapy may be indicated for the secondary prevention of other cardiovascular events that may coexist with AAA, it does not appear to affect the rate of growth or prevent rupture of aneurysms.46,47 In addition to aspirin, anticoagulants such as clopidogrel, enoxaparin, and warfarin are not recommended when the presence of AAA is the only indication.4
Other medications. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and antibiotics (eg, doxycycline) have been studied as a treatment for AAA. However, none has shown benefit in reducing aneurysm growth or rupture and they are not recommended for that sole purpose.4,48
Metformin. There is a negative association between diabetes and AAA expansion and rupture. Several cohort studies have indicated that this may be an independent effect driven primarily by exposure to metformin. While it is not unreasonable to consider this another important indication for metformin use in patients with diabetes, RCT evidence has yet to establish a role for metformin in patients without diabetes who have AAA.48,49
ACKNOWLEDGEMENT
The authors thank Gwen Wilson, MLS, AHIP, for her assistance with the literature searches performed in the preparation of this manuscript.
CORRESPONDENCE
Nicholas LeFevre, MD, Family and Community Medicine, University of Missouri–Columbia School of Medicine, One Hospital Drive, M224 Medical Science Building, Columbia, MO 65212; [email protected]
1. CDC. Wide-ranging Online Data for Epidemiologic Research (WONDER) database. Accessed August 30, 2023. https://wonder.cdc.gov/ucd-icd10.html
2. Reimerink JJ, van der Laan MJ, Koelemay MJ, et al. Systematic review and meta-analysis of population-based mortality from ruptured abdominal aortic aneurysm. Br J Surg. 2013;100:1405-1413. doi: 10.1002/bjs.9235
3. Kent KC. Clinical practice. Abdominal aortic aneurysms. N Engl J Med. 2014;371:2101-2108. doi: 10.1056/NEJMcp1401430
4. Chaikof EL, Dalman RL, Eskandari MK, et al. The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J Vasc Surg. 2018;67:2-77.e2. doi: 10.1016/j.jvs.2017.10.044
5. Moll FL, Powell JT, Fraedrich G, et al. Management of abdominal aortic aneurysms clinical practice guidelines of the European society for vascular surgery. Eur J Vasc Endovasc Surg. 2011;41 suppl 1:S1-S58. doi: 10.1016/j.ejvs.2010.09.011
6. Owens DK, Davidson KW, Krist AH, et al; US Preventive Services Task Force. Screening for abdominal aortic aneurysm: US Preventive Services Task Force recommendation statement. JAMA. 2019;322:2211-2218. doi: 10.1001/jama.2019.18928
7. National Institute for Health and Care Excellence. Abdominal aortic aneurysm: diagnosis and management. NICE guideline [NG156]. March 19, 2020. Accessed June 30, 2023. www.nice.org.uk/guidance/ng156/chapter/recommendations
8. Canadian Task Force on Preventive Health Care. Recommendations on screening for abdominal aortic aneurysm in primary care. CMAJ. 2017;189:E1137-E1145. doi: 10.1503/cmaj.170118
9. Abdulameer H, Al Taii H, Al-Kindi SG, et al. Epidemiology of fatal ruptured aortic aneurysms in the United States (1999-2016). J Vasc Surg. 2019;69:378-384.e2. doi: 10.1016/j.jvs.2018.03.435
10. Kent KC, Zwolak RM, Egorova NN, et al. Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals. J Vasc Surg. 2010;52:539-548. doi: 10.1016/j.jvs.2010.05.090
11. [No authors listed] Smoking, lung function and the prognosis of abdominal aortic aneurysm. The UK Small Aneurysm Trial Participants. Eur J Vasc Endovasc Surg. 2000;19:636-642. doi: 10.1053/ejvs.2000.1066
12. Oliver-Williams C, Sweeting MJ, Turton G, et al. Lessons learned about prevalence and growth rates of abdominal aortic aneurysms from a 25-year ultrasound population screening programme. Br J Surg. 2018;105:68-74. doi: 10.1002/bjs.10715
13. Ulug P, Powell JT, Sweeting MJ, et al. Meta-analysis of the current prevalence of screen-detected abdominal aortic aneurysm in women. Br J Surg. 2016;103:1097-1104. doi: 10.1002/bjs.10225
14. Chabok M, Nicolaides A, Aslam M, et al. Risk factors associated with increased prevalence of abdominal aortic aneurysm in women. Br J Surg. 2016;103:1132-1138. doi: 10.1002/bjs.10179
15. Sweeting, MJ, Masconi KL, Jones E, et al. Analysis of clinical benefit, harms, and cost-effectiveness of screening women for abdominal aortic aneurysm. Lancet. 2018;392:487-495. doi: 10.1016/S0140-6736(18)31222-4
16. Sweeting MJ, Thompson SG, Brown LC, et al; RESCAN collaborators. Meta-analysis of individual patient data to examine factors affecting growth and rupture of small abdominal aortic aneurysms. Br J Surg. 2012;99:655-665. doi: 10.1002/bjs.8707
17. Skibba AA, Evans JR, Hopkins SP, et al. Reconsidering gender relative to risk of rupture in the contemporary management of abdominal aortic aneurysms. J Vasc Surg. 2015;62:1429-1436. doi: 10.1016/j.jvs.2015.07.079
18. Guirguis-Blake JM, Beil TL, Senger CA, et al. Primary care screening for abdominal aortic aneurysm: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2019;322:2219-2238. doi: 10.1001/jama.2019.17021
19. Thompson SG, Ashton HA, Gao L, et al; Multicentre Aneurysm Screening Study (MASS) Group. Final follow-up of the Multicentre Aneurysm Screening Study (MASS) randomized trial of abdominal aortic aneurysm screening. Br J Surg. 2012;99:1649-1656. doi: 10.1002/bjs.8897
20. Ashton HA, Gao L, Kim LG, et al. Fifteen-year follow-up of a randomized clinical trial of ultrasonographic screening for abdominal aortic aneurysms. Br J Surg. 2007;94:696-701. doi: 10.1002/bjs.5780
21. Carnevale ML, Koleilat I, Lipsitz EC, et al. Extended screening guidelines for the diagnosis of abdominal aortic aneurysm. J Vasc Surg. 2020;72:1917-1926. doi: 10.1016/j.jvs.2020.03.047
22. Duncan A, Maslen C, Gibson C, et al. Ultrasound screening for abdominal aortic aneurysm in high-risk women. Br J Surg. 2021;108:1192-1198. doi: 10.1093/bjs/znab220
23. Shreibati JB, Baker LC, Hlatky MA, et al. Impact of the Screening Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act on abdominal ultrasonography use among Medicare beneficiaries. Arch Intern Med. 2012;172:1456-1462. doi: 10.1001/archinternmed.2012.4268
24. Hye RJ, Smith AE, Wong GH, et al. Leveraging the electronic medical record to implement an abdominal aortic aneurysm screening program. J Vasc Surg. 2014;59:1535-1542. doi: 10.1016/j.jvs.2013.12.016
25. Rubano E, Mehta N, Caputo W, et al., Systematic review: emergency department bedside ultrasonography for diagnosing suspected abdominal aortic aneurysm. Acad Emerg Med. 2013. 20:128-138. doi: 10.1111/acem.12080
26. Blois B. Office-based ultrasound screening for abdominal aortic aneurysm. Can Fam Physician. 2012;58:e172-e178.
27. Arnold MJ, Jonas CE, Carter RE. Point-of-care ultrasonography. Am Fam Physician. 2020;101:275-285.
28. Nixon G, Blattner K, Muirhead J, et al. Point-of-care ultrasound for FAST and AAA in rural New Zealand: quality and impact on patient care. Rural Remote Health. 2019;19:5027. doi: 10.22605/RRH5027
29. Lederle FA, Wilson SE, Johnson GR, et al. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1437-1444. doi: 10.1056/NEJMoa012573
30. Filardo G, Lederle FA, Ballard DJ, et al. Immediate open repair vs surveillance in patients with small abdominal aortic aneurysms: survival differences by aneurysm size. Mayo Clin Proc. 2013;88:910-919. doi: 10.1016/j.mayocp.2013.05.014
31. Lederle FA, Kyriakides TC, Stroupe KT, et al. Open versus endovascular repair of abdominal aortic aneurysm. N Engl J Med. 2019;380:2126-2135. doi: 10.1056/NEJMoa1715955
32. Patel R, Sweeting MJ, Powell JT, et al., Endovascular versus open repair of abdominal aortic aneurysm in 15-years’ follow-up of the UK endovascular aneurysm repair trial 1 (EVAR trial 1): a randomised controlled trial. Lancet. 2016;388:2366-2374. doi: 10.1016/S0140-6736(16)31135-7
33. van Schaik TG, Yeung KK, Verhagen HJ, et al. Long-term survival and secondary procedures after open or endovascular repair of abdominal aortic aneurysms. J Vasc Surg. 2017;66:1379-1389. doi: 10.1016/j.jvs.2017.05.122
34. Powell JT, Brady AR, Brown, LC, et al; United Kingdom Small Aneurysm Trial Participants. Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1445-1452. doi: 10.1056/NEJMoa013527
35. Paravastu SC, Jayarajasingam R, Cottam R, et al. Endovascular repair of abdominal aortic aneurysm. Cochrane Database Syst Rev. 2014:CD004178. doi: 10.1002/14651858.CD004178.pub2
36. Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;58:2020-2045. doi: 10.1016/j.jacc.2011.08.023
37. Bhak RH, Wininger M, Johnson GR, et al. Factors associated with small abdominal aortic aneurysm expansion rate. JAMA Surg. 2015;150:44-50. doi: 10.1001/jamasurg.2014.2025
38. Ouriel K, Clair DG, Kent KC, et al; Positive Impact of Endovascular Options for treating Aneurysms Early (PIVOTAL) Investigators. Endovascular repair compared with surveillance for patients with small abdominal aortic aneurysms. J Vasc Surg. 2010;51:1081-1087. doi: 10.1016/j.jvs.2009.10.113
39. Cao P, De Rango P, Verzini F, et al. Comparison of surveillance versus aortic endografting for small aneurysm repair (CAESAR): results from a randomised trial. Eur J Vasc Endovasc Surg. 2011;41:13-25. doi: 10.1016/j.ejvs.2010.08.026
40. Karthaus EG, Tong TML, Vahl A, et al; Dutch Society of Vascular Surgery, the Steering Committee of the Dutch Surgical Aneurysm Audit and the Dutch Institute for Clinical Auditing. Saccular abdominal aortic aneurysms: patient characteristics, clinical presentation, treatment, and outcomes in the Netherlands. Ann Surg. 2019;270:852-858. doi: 10.1097/SLA.0000000000003529
41. Nathan DP, Xu C, Pouch AM, et al. Increased wall stress of saccular versus fusiform aneurysms of the descending thoracic aorta. Ann Vasc Surg. 2011;25:1129-2237. doi: 10.1016/j.avsg.2011.07.008
42. Durojaye MS, Adeniyi TO, Alagbe OA. Multiple saccular aneurysms of the abdominal aorta: a case report and short review of risk factors for rupture on CT Scan. Ann Ib Postgrad Med. 2020;18:178-180.
43. Bertges DJ, Neal D, Schanzer A, et al. The Vascular Quality Initiative Cardiac Risk Index for prediction of myocardial infarction after vascular surgery. J Vasc Surg. 2016;64:1411-1421.e4. doi: 10.1016/j.jvs.2016.04.045
44. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111-188. doi: 10.1093/eurheartj/ehz455
45. Twine CP, Williams IM. Systematic review and meta-analysis of the effects of statin therapy on abdominal aortic aneurysms. Br J Surg. 2011;98:346-353. doi: 10.1002/bjs.7343
46. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140:e596-e646. doi: 10.1161/CIR.0000000000000678
47. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2014;35:2873-2926. doi: 10.1093/eurheartj/ehu281
48. Lederle FA, Noorbaloochi S, Nugent S, et al. Multicentre study of abdominal aortic aneurysm measurement and enlargement. Br J Surg. 2015;102:1480-1487. doi: 10.1002/bjs.9895
49. Itoga NK, Rothenberg KA, Suarez P, et al. Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population. J Vasc Surg. 2019;69:710-716.e3. doi: 10.1016/j.jvs.2018.06.19
Ruptured abdominal aortic aneurysms (AAAs) caused about 6000 deaths annually in the United States between 2014 and 20201 and are associated with a pooled mortality rate of 81%.2 They result from a distinct degenerative process of the layers of the aortic wall.2 An AAA is defined as an abdominal aorta whose dilation is > 50% normal (more commonly, a diameter > 3 cm).3,4 The risk for rupture correlates closely with size; most ruptures occur in aneurysms > 5.5 cm3,4 (TABLE 15).
Most AAAs are asymptomatic and often go undetected until rupture, resulting in poor outcomes. Because of a low and declining prevalence of AAA and ruptured AAA in developed countries, screening recommendations target high-risk groups rather than the general population.4,6-8 This review summarizes risk factors, prevalence, and current evidence-based screening and management recommendations for AAA.
Who’s at risk?
Age is the most significant nonmodifiable risk factor, with AAA rupture uncommon in patients younger than 55 years.9 One retrospective study found the odds ratio (OR) for diagnosing AAA was 9.41 in adults ages 65 to 69 years (95% CI, 8.76-10.12; P < .0001) and 14.46 (95% CI, 13.45-15.55; P < .0001) in adults ages 70 to 74 years, compared to adults younger than 55 years.10
Smoking is the most potent modifiable risk factor for AAA. Among patients with AAA, > 90% have a history of smoking.4 The association between smoking and AAA is dose dependent, with an OR of 2.61 (95% CI, 2.47-2.74) in patients with a pack-per-year history < 5 years and 12.13 (95% CI, 11.66-12.61) in patients with a pack-per-year history > 35 years, compared to nonsmokers.10 The risk for AAA increases with smoking duration but decreases with cessation duration.4,10 Smoking cessation remains an important intervention, as active smokers have higher AAA rupture rates.11
Other risk factors for AAA include concomitant cardiovascular disease (CVD) such as coronary artery disease (CAD), cerebrovascular disease, atherosclerosis, dyslipidemia, and hypertension.10 Factors associated with reduced risk for AAA include African American race, Hispanic ethnicity, Asian ethnicity, diabetes, smoking cessation, consuming fruits and vegetables > 3 times per week, and exercising more than once per week.6,10
Prevalence declines but sex-based disparities in outcomes persist
The prevalence of AAA has declined in the United States and Europe in recent decades, correlating with declining rates of smoking.4,12 Reports published between 2011 and 2019 estimate that AAA prevalence in men older than 60 years has declined over time, with a prevalence of 1.2% to 3.3%.6 The prevalence of AAA has also decreased in women,6,13,14 estimated in 1 study to be as low as 0.74%.13 Similarly, deaths from ruptured AAA have declined markedly in the United States—by 70% between 1999 and 2016 according to 1 analysis.9
One striking difference in the male-female data is that although AAAs are more common in men, there is a 2- to 4-fold higher risk for rupture in women, who account for nearly half of all AAA-related deaths.9,10,15-17 The reasons for this heightened risk to women despite lower prevalence are not fully understood but are likely multifactorial and related to a general lack of screening for AAA in women, tendency for AAA to rupture at smaller diameters in women, rupture at an older age in women, and a history of worse surgical outcomes in women than men (though the gap in surgical outcomes appears to be closing).9,10,18
Continue to: While declines in AAA and AAA-related...
While declines in AAA and AAA-related death are largely attributed to lower smoking rates, other likely contributing factors include the implementation of screening programs, incidental detection during cross-sectional imaging, and improved surgical techniques and management of CV risk factors (eg, hypertension, hyperlipidemia).9,10
The benefits of screening older men
Randomized controlled trials (RCTs) have demonstrated the benefits of AAA screening programs. A meta-analysis of 4 populationbased RCTs of AAA screening in men ≥ 65 years demonstrated statistically significant reductions in AAA rupture (OR = 0.62; 95% CI, 0.55-0.70) and death from AAA (OR = 0.65; 95% CI, 0.57-0.74) over 12 to 15 years, with a number needed to screen (NNS) of 305 (95% CI, 248-411) to prevent 1 AAA-related death.18 The study also found screening decreases the rate of emergent surgeries for AAA (OR = 0.57; 95% CI, 0.48-0.68) while increasing the number of elective surgeries (OR = 1.44; 95% CI, 1.34-1.55) over 4 to 15 years.18
Only 1 study has demonstrated an improvement in all-cause mortality with screening programs, with a relatively small benefit (OR = 0.97; 95% CI, 0.94-0.99).19 Only 1 of the studies included women and, while underpowered, showed no difference in AAA-related death or rupture.20 Guidelines and recommendations of various countries and professional societies focus screening on subgroups at highest risk for AAA.4,6-8,18
Screening recommendations from USPSTF and others
The US Preventive Services Task Force (USPSTF) currently recommends one-time ultrasound screening for AAA in men ages 65 to 75 years who have ever smoked (commonly defined as having smoked > 100 cigarettes) in their lifetime.6 This grade “B” recommendation, initially made in 2005 and reaffirmed in the 2014 and 2019 USPSTF updates, recommends screening the highest-risk segment of the population (ie, older male smokers).
In men ages 65 to 75 years with no smoking history, rather than routine screening, the USPSTF recommends selectively offering screening based on the patient’s medical history, family history, risk factors, and personal values (with a “C” grade).6 The USPSTF continues to recommend against screening for AAA in women with no smoking history and no family history of AAA.6 According to the USPSTF, the evidence is insufficient to recommend for or against screening women ages 65 to 75 years who have ever smoked or have a family history of AAA (“I” statement).6
Continue to: One critique of the USPSTF recommendations
One critique of the USPSTF recommendations is that they fail to detect a significant portion of patients with AAA and AAA rupture. For example, in a retrospective analysis of 55,197 patients undergoing AAA repair, only 33% would have been detected by the USPSTF grade “B” recommendation to screen male smokers ages 65 to 75 years, and an analysis of AAA-related fatalities found 43% would be missed by USPSTF criteria.9,21
Screening guidelines from the Society for Vascular Surgery (SVS) are broader than those of the USPSTF, in an attempt to capture a larger percentage of the population at risk for AAA-related disease by extrapolating from epidemiologic data. The SVS guidelines include screening for women ages 65 to 75 years with a smoking history, screening men and women ages 65 to 75 years who have a first-degree relative with AAA, and consideration of screening patients older than 75 years if they are in good health and have a first-degree relative with AAA or a smoking history and have not been previously screened.4 However, these expanded recommendations are not supported by patient-oriented evidence.6
Attempts to broaden screening guidelines must be tempered by potential risks for harm, primarily overdiagnosis (ie, diagnosing AAAs that would not otherwise rise to clinical significance) and overtreatment (ie, resulting in unnecessary imaging, appointments, anxiety, or surgery). Negative psychological effects on quality of life after a diagnosis of AAA have not been shown to cause significant harm.6,18
A recent UK analysis found that screening programs for AAA in women modeled after those in men are not cost effective, with an NNS to prevent 1 death of 3900 in women vs 700 in men.15,18 Another recent trial of ultrasound screening in 5200 high-risk women ages 65 to 74 years found an AAA incidence of 0.29% (95% CI, 0.18%-0.48%) in which only 3 large aneurysms were identified.22
In the United States, rates of screening for AAA remain low.23 One study has shown electronic medical record–based reminders increased screening rates from 48% to 80%.24 Point-of-care bedside ultrasound performed by clinicians also could improve screening rates. Multiple studies have demonstrated that screening and diagnosis of AAA can be performed safely and effectively at the bedside by nonradiologists such as family physicians and emergency physicians.25-28 In 1 study, such exams added < 4 minutes to the patient encounter.26 Follow-up surveillance schedules for those identified as having a AAA are summarized in TABLE 2.4
Continue to: Management options
Management options: Immediate repair or surveillance?
After diagnosing AAA, important decisions must be made regarding management, including indications for surgical repair, appropriate follow-up surveillance, and medications for secondary prevention and cardiovascular risk reduction.
EVAR vs open repair
The 2 main surgical strategies for aneurysm repair are open repair and endovascular repair (EVAR). In the United States, EVAR is becoming the more common approach and was used to repair asymptomatic aneurysms in > 80% of patients and ruptured aneurysms in 50% of patients.6 There have been multiple RCTs assessing EVAR and open repair for large and small aneurysms.29-34 Findings across these studies consistently show EVAR is associated with lower immediate (ie, 30-day) morbidity and mortality but no longer-term survival benefit compared to open repair.
EVAR procedures require ongoing long-term surveillance for endovascular leakage and other complications, resulting in an increased need for re-intervention.31,33,35 For these reasons, the National Institute for Health and Care Excellence (NICE) guidelines suggest open repair as the preferred modality.7 However, SVS and the American College of Cardiology Foundation/American Heart Association guidance support either EVAR or open repair, noting that open repair may be preferable in patients unable to engage in long-term follow-up surveillance.36
Indications for repair. In general, repair is indicated when an aneurysm reaches or exceeds 5.5 cm.4,7 Both SVS and NICE also recommend clinicians consider surgical repair of smaller, rapidly expanding aneurysms (> 1 cm over a 1-year period).4,7 Based on evidence suggesting a higher risk for rupture in women with smaller aneurysms,14,37 SVS recommends clinicians consider surgical repair in women with an AAA ≥ 5.0 cm. Several RCTs evaluating the benefits of immediate repair for smaller-sized aneurysms (4.0-5.5 cm) favored surveillance.38,39 Accepted indications for surgical repair are summarized in TABLE 3.4,7,34Surgical repair recommendations also are based on aneurysm morphology, which can be fusiform or saccular (FIGURE). More than 90% of AAAs are fusiform.40 Although saccular AAAs are less common, some studies suggest they are more prone to rupture than fusiform AAAs, and SVS guidelines suggest surgical repair of saccular aneurysms regardless of size.4,41,42
Perioperative and long-term risks. Both EVAR and open repair of AAA carry a high perioperative and long-term risk for death, as patients often have multiple comorbidities. A 2019 trial comparing EVAR to open repair with 14 years of follow-up reported death in 68% of patients in the EVAR group and 70% in the open repair group. 31 Among these deaths, 2.7% in the EVAR group and 3.7% in the open repair group were aneurysm related.31 The study also found a second surgical intervention was required in 19.8% of patients in the open repair group and 26.7% in the EVAR group.31
Continue to: When assessing perioperative risk...
When assessing perioperative risk, SVS guidelines recommend clinicians employ a shared decision-making approach with patients that incorporates Vascular Quality Initiative (VQI) mortality risk score.4 (VQI risk calculators are available at https://qxmd.com/vascular-study-group-new-england-decision-support-tools.43)
Medication management
Based on the close association of aortic aneurysm with atherosclerotic CVD (ASCVD), professional societies such as the European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) have suggested aortic aneurysm is equivalent to ASCVD and should be managed medically in a similar manner to peripheral arterial disease.44 Indeed, many patients with AAA may have concomitant CAD or other arterial vascular diseases (eg, carotid, lower extremity).
Statins. In its guidelines, the ESC/EAS consider patients with AAA at “very high risk” for adverse CV events and suggest pharmacotherapy with high-intensity statins, adding ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors if needed, to reduce low-density lipoprotein cholesterol ≥ 50% from baseline, with a goal of < 55 mg/dL.44 Statin therapy additionally lowers all-cause postoperative mortality in patients undergoing AAA repair but does not affect the rate of aneurysm expansion.45
Aspirin and other anticoagulants. Although aspirin therapy may be indicated for the secondary prevention of other cardiovascular events that may coexist with AAA, it does not appear to affect the rate of growth or prevent rupture of aneurysms.46,47 In addition to aspirin, anticoagulants such as clopidogrel, enoxaparin, and warfarin are not recommended when the presence of AAA is the only indication.4
Other medications. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and antibiotics (eg, doxycycline) have been studied as a treatment for AAA. However, none has shown benefit in reducing aneurysm growth or rupture and they are not recommended for that sole purpose.4,48
Metformin. There is a negative association between diabetes and AAA expansion and rupture. Several cohort studies have indicated that this may be an independent effect driven primarily by exposure to metformin. While it is not unreasonable to consider this another important indication for metformin use in patients with diabetes, RCT evidence has yet to establish a role for metformin in patients without diabetes who have AAA.48,49
ACKNOWLEDGEMENT
The authors thank Gwen Wilson, MLS, AHIP, for her assistance with the literature searches performed in the preparation of this manuscript.
CORRESPONDENCE
Nicholas LeFevre, MD, Family and Community Medicine, University of Missouri–Columbia School of Medicine, One Hospital Drive, M224 Medical Science Building, Columbia, MO 65212; [email protected]
Ruptured abdominal aortic aneurysms (AAAs) caused about 6000 deaths annually in the United States between 2014 and 20201 and are associated with a pooled mortality rate of 81%.2 They result from a distinct degenerative process of the layers of the aortic wall.2 An AAA is defined as an abdominal aorta whose dilation is > 50% normal (more commonly, a diameter > 3 cm).3,4 The risk for rupture correlates closely with size; most ruptures occur in aneurysms > 5.5 cm3,4 (TABLE 15).
Most AAAs are asymptomatic and often go undetected until rupture, resulting in poor outcomes. Because of a low and declining prevalence of AAA and ruptured AAA in developed countries, screening recommendations target high-risk groups rather than the general population.4,6-8 This review summarizes risk factors, prevalence, and current evidence-based screening and management recommendations for AAA.
Who’s at risk?
Age is the most significant nonmodifiable risk factor, with AAA rupture uncommon in patients younger than 55 years.9 One retrospective study found the odds ratio (OR) for diagnosing AAA was 9.41 in adults ages 65 to 69 years (95% CI, 8.76-10.12; P < .0001) and 14.46 (95% CI, 13.45-15.55; P < .0001) in adults ages 70 to 74 years, compared to adults younger than 55 years.10
Smoking is the most potent modifiable risk factor for AAA. Among patients with AAA, > 90% have a history of smoking.4 The association between smoking and AAA is dose dependent, with an OR of 2.61 (95% CI, 2.47-2.74) in patients with a pack-per-year history < 5 years and 12.13 (95% CI, 11.66-12.61) in patients with a pack-per-year history > 35 years, compared to nonsmokers.10 The risk for AAA increases with smoking duration but decreases with cessation duration.4,10 Smoking cessation remains an important intervention, as active smokers have higher AAA rupture rates.11
Other risk factors for AAA include concomitant cardiovascular disease (CVD) such as coronary artery disease (CAD), cerebrovascular disease, atherosclerosis, dyslipidemia, and hypertension.10 Factors associated with reduced risk for AAA include African American race, Hispanic ethnicity, Asian ethnicity, diabetes, smoking cessation, consuming fruits and vegetables > 3 times per week, and exercising more than once per week.6,10
Prevalence declines but sex-based disparities in outcomes persist
The prevalence of AAA has declined in the United States and Europe in recent decades, correlating with declining rates of smoking.4,12 Reports published between 2011 and 2019 estimate that AAA prevalence in men older than 60 years has declined over time, with a prevalence of 1.2% to 3.3%.6 The prevalence of AAA has also decreased in women,6,13,14 estimated in 1 study to be as low as 0.74%.13 Similarly, deaths from ruptured AAA have declined markedly in the United States—by 70% between 1999 and 2016 according to 1 analysis.9
One striking difference in the male-female data is that although AAAs are more common in men, there is a 2- to 4-fold higher risk for rupture in women, who account for nearly half of all AAA-related deaths.9,10,15-17 The reasons for this heightened risk to women despite lower prevalence are not fully understood but are likely multifactorial and related to a general lack of screening for AAA in women, tendency for AAA to rupture at smaller diameters in women, rupture at an older age in women, and a history of worse surgical outcomes in women than men (though the gap in surgical outcomes appears to be closing).9,10,18
Continue to: While declines in AAA and AAA-related...
While declines in AAA and AAA-related death are largely attributed to lower smoking rates, other likely contributing factors include the implementation of screening programs, incidental detection during cross-sectional imaging, and improved surgical techniques and management of CV risk factors (eg, hypertension, hyperlipidemia).9,10
The benefits of screening older men
Randomized controlled trials (RCTs) have demonstrated the benefits of AAA screening programs. A meta-analysis of 4 populationbased RCTs of AAA screening in men ≥ 65 years demonstrated statistically significant reductions in AAA rupture (OR = 0.62; 95% CI, 0.55-0.70) and death from AAA (OR = 0.65; 95% CI, 0.57-0.74) over 12 to 15 years, with a number needed to screen (NNS) of 305 (95% CI, 248-411) to prevent 1 AAA-related death.18 The study also found screening decreases the rate of emergent surgeries for AAA (OR = 0.57; 95% CI, 0.48-0.68) while increasing the number of elective surgeries (OR = 1.44; 95% CI, 1.34-1.55) over 4 to 15 years.18
Only 1 study has demonstrated an improvement in all-cause mortality with screening programs, with a relatively small benefit (OR = 0.97; 95% CI, 0.94-0.99).19 Only 1 of the studies included women and, while underpowered, showed no difference in AAA-related death or rupture.20 Guidelines and recommendations of various countries and professional societies focus screening on subgroups at highest risk for AAA.4,6-8,18
Screening recommendations from USPSTF and others
The US Preventive Services Task Force (USPSTF) currently recommends one-time ultrasound screening for AAA in men ages 65 to 75 years who have ever smoked (commonly defined as having smoked > 100 cigarettes) in their lifetime.6 This grade “B” recommendation, initially made in 2005 and reaffirmed in the 2014 and 2019 USPSTF updates, recommends screening the highest-risk segment of the population (ie, older male smokers).
In men ages 65 to 75 years with no smoking history, rather than routine screening, the USPSTF recommends selectively offering screening based on the patient’s medical history, family history, risk factors, and personal values (with a “C” grade).6 The USPSTF continues to recommend against screening for AAA in women with no smoking history and no family history of AAA.6 According to the USPSTF, the evidence is insufficient to recommend for or against screening women ages 65 to 75 years who have ever smoked or have a family history of AAA (“I” statement).6
Continue to: One critique of the USPSTF recommendations
One critique of the USPSTF recommendations is that they fail to detect a significant portion of patients with AAA and AAA rupture. For example, in a retrospective analysis of 55,197 patients undergoing AAA repair, only 33% would have been detected by the USPSTF grade “B” recommendation to screen male smokers ages 65 to 75 years, and an analysis of AAA-related fatalities found 43% would be missed by USPSTF criteria.9,21
Screening guidelines from the Society for Vascular Surgery (SVS) are broader than those of the USPSTF, in an attempt to capture a larger percentage of the population at risk for AAA-related disease by extrapolating from epidemiologic data. The SVS guidelines include screening for women ages 65 to 75 years with a smoking history, screening men and women ages 65 to 75 years who have a first-degree relative with AAA, and consideration of screening patients older than 75 years if they are in good health and have a first-degree relative with AAA or a smoking history and have not been previously screened.4 However, these expanded recommendations are not supported by patient-oriented evidence.6
Attempts to broaden screening guidelines must be tempered by potential risks for harm, primarily overdiagnosis (ie, diagnosing AAAs that would not otherwise rise to clinical significance) and overtreatment (ie, resulting in unnecessary imaging, appointments, anxiety, or surgery). Negative psychological effects on quality of life after a diagnosis of AAA have not been shown to cause significant harm.6,18
A recent UK analysis found that screening programs for AAA in women modeled after those in men are not cost effective, with an NNS to prevent 1 death of 3900 in women vs 700 in men.15,18 Another recent trial of ultrasound screening in 5200 high-risk women ages 65 to 74 years found an AAA incidence of 0.29% (95% CI, 0.18%-0.48%) in which only 3 large aneurysms were identified.22
In the United States, rates of screening for AAA remain low.23 One study has shown electronic medical record–based reminders increased screening rates from 48% to 80%.24 Point-of-care bedside ultrasound performed by clinicians also could improve screening rates. Multiple studies have demonstrated that screening and diagnosis of AAA can be performed safely and effectively at the bedside by nonradiologists such as family physicians and emergency physicians.25-28 In 1 study, such exams added < 4 minutes to the patient encounter.26 Follow-up surveillance schedules for those identified as having a AAA are summarized in TABLE 2.4
Continue to: Management options
Management options: Immediate repair or surveillance?
After diagnosing AAA, important decisions must be made regarding management, including indications for surgical repair, appropriate follow-up surveillance, and medications for secondary prevention and cardiovascular risk reduction.
EVAR vs open repair
The 2 main surgical strategies for aneurysm repair are open repair and endovascular repair (EVAR). In the United States, EVAR is becoming the more common approach and was used to repair asymptomatic aneurysms in > 80% of patients and ruptured aneurysms in 50% of patients.6 There have been multiple RCTs assessing EVAR and open repair for large and small aneurysms.29-34 Findings across these studies consistently show EVAR is associated with lower immediate (ie, 30-day) morbidity and mortality but no longer-term survival benefit compared to open repair.
EVAR procedures require ongoing long-term surveillance for endovascular leakage and other complications, resulting in an increased need for re-intervention.31,33,35 For these reasons, the National Institute for Health and Care Excellence (NICE) guidelines suggest open repair as the preferred modality.7 However, SVS and the American College of Cardiology Foundation/American Heart Association guidance support either EVAR or open repair, noting that open repair may be preferable in patients unable to engage in long-term follow-up surveillance.36
Indications for repair. In general, repair is indicated when an aneurysm reaches or exceeds 5.5 cm.4,7 Both SVS and NICE also recommend clinicians consider surgical repair of smaller, rapidly expanding aneurysms (> 1 cm over a 1-year period).4,7 Based on evidence suggesting a higher risk for rupture in women with smaller aneurysms,14,37 SVS recommends clinicians consider surgical repair in women with an AAA ≥ 5.0 cm. Several RCTs evaluating the benefits of immediate repair for smaller-sized aneurysms (4.0-5.5 cm) favored surveillance.38,39 Accepted indications for surgical repair are summarized in TABLE 3.4,7,34Surgical repair recommendations also are based on aneurysm morphology, which can be fusiform or saccular (FIGURE). More than 90% of AAAs are fusiform.40 Although saccular AAAs are less common, some studies suggest they are more prone to rupture than fusiform AAAs, and SVS guidelines suggest surgical repair of saccular aneurysms regardless of size.4,41,42
Perioperative and long-term risks. Both EVAR and open repair of AAA carry a high perioperative and long-term risk for death, as patients often have multiple comorbidities. A 2019 trial comparing EVAR to open repair with 14 years of follow-up reported death in 68% of patients in the EVAR group and 70% in the open repair group. 31 Among these deaths, 2.7% in the EVAR group and 3.7% in the open repair group were aneurysm related.31 The study also found a second surgical intervention was required in 19.8% of patients in the open repair group and 26.7% in the EVAR group.31
Continue to: When assessing perioperative risk...
When assessing perioperative risk, SVS guidelines recommend clinicians employ a shared decision-making approach with patients that incorporates Vascular Quality Initiative (VQI) mortality risk score.4 (VQI risk calculators are available at https://qxmd.com/vascular-study-group-new-england-decision-support-tools.43)
Medication management
Based on the close association of aortic aneurysm with atherosclerotic CVD (ASCVD), professional societies such as the European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) have suggested aortic aneurysm is equivalent to ASCVD and should be managed medically in a similar manner to peripheral arterial disease.44 Indeed, many patients with AAA may have concomitant CAD or other arterial vascular diseases (eg, carotid, lower extremity).
Statins. In its guidelines, the ESC/EAS consider patients with AAA at “very high risk” for adverse CV events and suggest pharmacotherapy with high-intensity statins, adding ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors if needed, to reduce low-density lipoprotein cholesterol ≥ 50% from baseline, with a goal of < 55 mg/dL.44 Statin therapy additionally lowers all-cause postoperative mortality in patients undergoing AAA repair but does not affect the rate of aneurysm expansion.45
Aspirin and other anticoagulants. Although aspirin therapy may be indicated for the secondary prevention of other cardiovascular events that may coexist with AAA, it does not appear to affect the rate of growth or prevent rupture of aneurysms.46,47 In addition to aspirin, anticoagulants such as clopidogrel, enoxaparin, and warfarin are not recommended when the presence of AAA is the only indication.4
Other medications. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and antibiotics (eg, doxycycline) have been studied as a treatment for AAA. However, none has shown benefit in reducing aneurysm growth or rupture and they are not recommended for that sole purpose.4,48
Metformin. There is a negative association between diabetes and AAA expansion and rupture. Several cohort studies have indicated that this may be an independent effect driven primarily by exposure to metformin. While it is not unreasonable to consider this another important indication for metformin use in patients with diabetes, RCT evidence has yet to establish a role for metformin in patients without diabetes who have AAA.48,49
ACKNOWLEDGEMENT
The authors thank Gwen Wilson, MLS, AHIP, for her assistance with the literature searches performed in the preparation of this manuscript.
CORRESPONDENCE
Nicholas LeFevre, MD, Family and Community Medicine, University of Missouri–Columbia School of Medicine, One Hospital Drive, M224 Medical Science Building, Columbia, MO 65212; [email protected]
1. CDC. Wide-ranging Online Data for Epidemiologic Research (WONDER) database. Accessed August 30, 2023. https://wonder.cdc.gov/ucd-icd10.html
2. Reimerink JJ, van der Laan MJ, Koelemay MJ, et al. Systematic review and meta-analysis of population-based mortality from ruptured abdominal aortic aneurysm. Br J Surg. 2013;100:1405-1413. doi: 10.1002/bjs.9235
3. Kent KC. Clinical practice. Abdominal aortic aneurysms. N Engl J Med. 2014;371:2101-2108. doi: 10.1056/NEJMcp1401430
4. Chaikof EL, Dalman RL, Eskandari MK, et al. The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J Vasc Surg. 2018;67:2-77.e2. doi: 10.1016/j.jvs.2017.10.044
5. Moll FL, Powell JT, Fraedrich G, et al. Management of abdominal aortic aneurysms clinical practice guidelines of the European society for vascular surgery. Eur J Vasc Endovasc Surg. 2011;41 suppl 1:S1-S58. doi: 10.1016/j.ejvs.2010.09.011
6. Owens DK, Davidson KW, Krist AH, et al; US Preventive Services Task Force. Screening for abdominal aortic aneurysm: US Preventive Services Task Force recommendation statement. JAMA. 2019;322:2211-2218. doi: 10.1001/jama.2019.18928
7. National Institute for Health and Care Excellence. Abdominal aortic aneurysm: diagnosis and management. NICE guideline [NG156]. March 19, 2020. Accessed June 30, 2023. www.nice.org.uk/guidance/ng156/chapter/recommendations
8. Canadian Task Force on Preventive Health Care. Recommendations on screening for abdominal aortic aneurysm in primary care. CMAJ. 2017;189:E1137-E1145. doi: 10.1503/cmaj.170118
9. Abdulameer H, Al Taii H, Al-Kindi SG, et al. Epidemiology of fatal ruptured aortic aneurysms in the United States (1999-2016). J Vasc Surg. 2019;69:378-384.e2. doi: 10.1016/j.jvs.2018.03.435
10. Kent KC, Zwolak RM, Egorova NN, et al. Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals. J Vasc Surg. 2010;52:539-548. doi: 10.1016/j.jvs.2010.05.090
11. [No authors listed] Smoking, lung function and the prognosis of abdominal aortic aneurysm. The UK Small Aneurysm Trial Participants. Eur J Vasc Endovasc Surg. 2000;19:636-642. doi: 10.1053/ejvs.2000.1066
12. Oliver-Williams C, Sweeting MJ, Turton G, et al. Lessons learned about prevalence and growth rates of abdominal aortic aneurysms from a 25-year ultrasound population screening programme. Br J Surg. 2018;105:68-74. doi: 10.1002/bjs.10715
13. Ulug P, Powell JT, Sweeting MJ, et al. Meta-analysis of the current prevalence of screen-detected abdominal aortic aneurysm in women. Br J Surg. 2016;103:1097-1104. doi: 10.1002/bjs.10225
14. Chabok M, Nicolaides A, Aslam M, et al. Risk factors associated with increased prevalence of abdominal aortic aneurysm in women. Br J Surg. 2016;103:1132-1138. doi: 10.1002/bjs.10179
15. Sweeting, MJ, Masconi KL, Jones E, et al. Analysis of clinical benefit, harms, and cost-effectiveness of screening women for abdominal aortic aneurysm. Lancet. 2018;392:487-495. doi: 10.1016/S0140-6736(18)31222-4
16. Sweeting MJ, Thompson SG, Brown LC, et al; RESCAN collaborators. Meta-analysis of individual patient data to examine factors affecting growth and rupture of small abdominal aortic aneurysms. Br J Surg. 2012;99:655-665. doi: 10.1002/bjs.8707
17. Skibba AA, Evans JR, Hopkins SP, et al. Reconsidering gender relative to risk of rupture in the contemporary management of abdominal aortic aneurysms. J Vasc Surg. 2015;62:1429-1436. doi: 10.1016/j.jvs.2015.07.079
18. Guirguis-Blake JM, Beil TL, Senger CA, et al. Primary care screening for abdominal aortic aneurysm: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2019;322:2219-2238. doi: 10.1001/jama.2019.17021
19. Thompson SG, Ashton HA, Gao L, et al; Multicentre Aneurysm Screening Study (MASS) Group. Final follow-up of the Multicentre Aneurysm Screening Study (MASS) randomized trial of abdominal aortic aneurysm screening. Br J Surg. 2012;99:1649-1656. doi: 10.1002/bjs.8897
20. Ashton HA, Gao L, Kim LG, et al. Fifteen-year follow-up of a randomized clinical trial of ultrasonographic screening for abdominal aortic aneurysms. Br J Surg. 2007;94:696-701. doi: 10.1002/bjs.5780
21. Carnevale ML, Koleilat I, Lipsitz EC, et al. Extended screening guidelines for the diagnosis of abdominal aortic aneurysm. J Vasc Surg. 2020;72:1917-1926. doi: 10.1016/j.jvs.2020.03.047
22. Duncan A, Maslen C, Gibson C, et al. Ultrasound screening for abdominal aortic aneurysm in high-risk women. Br J Surg. 2021;108:1192-1198. doi: 10.1093/bjs/znab220
23. Shreibati JB, Baker LC, Hlatky MA, et al. Impact of the Screening Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act on abdominal ultrasonography use among Medicare beneficiaries. Arch Intern Med. 2012;172:1456-1462. doi: 10.1001/archinternmed.2012.4268
24. Hye RJ, Smith AE, Wong GH, et al. Leveraging the electronic medical record to implement an abdominal aortic aneurysm screening program. J Vasc Surg. 2014;59:1535-1542. doi: 10.1016/j.jvs.2013.12.016
25. Rubano E, Mehta N, Caputo W, et al., Systematic review: emergency department bedside ultrasonography for diagnosing suspected abdominal aortic aneurysm. Acad Emerg Med. 2013. 20:128-138. doi: 10.1111/acem.12080
26. Blois B. Office-based ultrasound screening for abdominal aortic aneurysm. Can Fam Physician. 2012;58:e172-e178.
27. Arnold MJ, Jonas CE, Carter RE. Point-of-care ultrasonography. Am Fam Physician. 2020;101:275-285.
28. Nixon G, Blattner K, Muirhead J, et al. Point-of-care ultrasound for FAST and AAA in rural New Zealand: quality and impact on patient care. Rural Remote Health. 2019;19:5027. doi: 10.22605/RRH5027
29. Lederle FA, Wilson SE, Johnson GR, et al. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1437-1444. doi: 10.1056/NEJMoa012573
30. Filardo G, Lederle FA, Ballard DJ, et al. Immediate open repair vs surveillance in patients with small abdominal aortic aneurysms: survival differences by aneurysm size. Mayo Clin Proc. 2013;88:910-919. doi: 10.1016/j.mayocp.2013.05.014
31. Lederle FA, Kyriakides TC, Stroupe KT, et al. Open versus endovascular repair of abdominal aortic aneurysm. N Engl J Med. 2019;380:2126-2135. doi: 10.1056/NEJMoa1715955
32. Patel R, Sweeting MJ, Powell JT, et al., Endovascular versus open repair of abdominal aortic aneurysm in 15-years’ follow-up of the UK endovascular aneurysm repair trial 1 (EVAR trial 1): a randomised controlled trial. Lancet. 2016;388:2366-2374. doi: 10.1016/S0140-6736(16)31135-7
33. van Schaik TG, Yeung KK, Verhagen HJ, et al. Long-term survival and secondary procedures after open or endovascular repair of abdominal aortic aneurysms. J Vasc Surg. 2017;66:1379-1389. doi: 10.1016/j.jvs.2017.05.122
34. Powell JT, Brady AR, Brown, LC, et al; United Kingdom Small Aneurysm Trial Participants. Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1445-1452. doi: 10.1056/NEJMoa013527
35. Paravastu SC, Jayarajasingam R, Cottam R, et al. Endovascular repair of abdominal aortic aneurysm. Cochrane Database Syst Rev. 2014:CD004178. doi: 10.1002/14651858.CD004178.pub2
36. Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;58:2020-2045. doi: 10.1016/j.jacc.2011.08.023
37. Bhak RH, Wininger M, Johnson GR, et al. Factors associated with small abdominal aortic aneurysm expansion rate. JAMA Surg. 2015;150:44-50. doi: 10.1001/jamasurg.2014.2025
38. Ouriel K, Clair DG, Kent KC, et al; Positive Impact of Endovascular Options for treating Aneurysms Early (PIVOTAL) Investigators. Endovascular repair compared with surveillance for patients with small abdominal aortic aneurysms. J Vasc Surg. 2010;51:1081-1087. doi: 10.1016/j.jvs.2009.10.113
39. Cao P, De Rango P, Verzini F, et al. Comparison of surveillance versus aortic endografting for small aneurysm repair (CAESAR): results from a randomised trial. Eur J Vasc Endovasc Surg. 2011;41:13-25. doi: 10.1016/j.ejvs.2010.08.026
40. Karthaus EG, Tong TML, Vahl A, et al; Dutch Society of Vascular Surgery, the Steering Committee of the Dutch Surgical Aneurysm Audit and the Dutch Institute for Clinical Auditing. Saccular abdominal aortic aneurysms: patient characteristics, clinical presentation, treatment, and outcomes in the Netherlands. Ann Surg. 2019;270:852-858. doi: 10.1097/SLA.0000000000003529
41. Nathan DP, Xu C, Pouch AM, et al. Increased wall stress of saccular versus fusiform aneurysms of the descending thoracic aorta. Ann Vasc Surg. 2011;25:1129-2237. doi: 10.1016/j.avsg.2011.07.008
42. Durojaye MS, Adeniyi TO, Alagbe OA. Multiple saccular aneurysms of the abdominal aorta: a case report and short review of risk factors for rupture on CT Scan. Ann Ib Postgrad Med. 2020;18:178-180.
43. Bertges DJ, Neal D, Schanzer A, et al. The Vascular Quality Initiative Cardiac Risk Index for prediction of myocardial infarction after vascular surgery. J Vasc Surg. 2016;64:1411-1421.e4. doi: 10.1016/j.jvs.2016.04.045
44. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111-188. doi: 10.1093/eurheartj/ehz455
45. Twine CP, Williams IM. Systematic review and meta-analysis of the effects of statin therapy on abdominal aortic aneurysms. Br J Surg. 2011;98:346-353. doi: 10.1002/bjs.7343
46. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140:e596-e646. doi: 10.1161/CIR.0000000000000678
47. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2014;35:2873-2926. doi: 10.1093/eurheartj/ehu281
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49. Itoga NK, Rothenberg KA, Suarez P, et al. Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population. J Vasc Surg. 2019;69:710-716.e3. doi: 10.1016/j.jvs.2018.06.19
PRACTICE RECOMMENDATIONS
› Perform a one-time abdominal aortic aneurysm (AAA) screening ultrasound in men ages 65 to 75 years who have ever smoked. B
› Consider performing a one-time AAA screening ultrasound in women ages 65 to 75 years who have ever smoked. C
› Prescribe high-intensity statin therapy for men and women with atherosclerotic AAA. A
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
