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Goodbye CHADSVASc: Sex Complicates Stroke Risk Scoring in AF
The European Society of Cardiology (ESC) caused a stir when they recommended in their latest atrial fibrillation (AF) management guideline that gender no longer be included in the decision to initiate oral anticoagulation therapy.
The move aims to level the playing field between men and women and follows a more nuanced understanding of stroke risk in patients with AF, said experts. It also acknowledges the lack of evidence in people receiving cross-sex hormone therapy.
In any case, the guidelines, developed in collaboration with the European Association for Cardio-Thoracic Surgery and published by the European Heart Journal on August 30, simply follow 2023’s US recommendations, they added.
One Size Does Not Fit All
So, what to the ESC guidelines actually say?
They underline that, if left untreated, the risk for ischemic stroke is increased fivefold in patients with AF, and the “default approach should therefore be to provide oral anticoagulation to all eligible AF patients, except those at low risk for incident stroke or thromboembolism.”
However, the authors note that there is a lack of strong evidence on how to apply the current risk scores to help inform that decision in real-world patients.
Dipak Kotecha, MBChB, PhD, Professor of Cardiology at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, England, and senior author of the ESC guidelines, said in an interview that “the available scores have a relatively poor ability to accurately predict which patients will have a stroke or thromboembolic event.”
Instead, he said “a much better approach is for healthcare professionals to look at each patient’s individual risk factors, using the risk scores to identify those patients that might not benefit from oral anticoagulant therapy.”
For these guidelines, the authors therefore wanted to “move away from a one-size-fits-all” approach, Kotecha said, and instead ensure that more patients can benefit from the new range of direct oral anticoagulants (DOACs) that are easier to take and with much lower chance of side effects or major bleeding.
To achieve this, they separated their clinical recommendations from any particular risk score, and instead focused on the practicalities of implementation.
Risk Modifier Vs Risk Factor
To explain their decision the authors highlight that “the most popular risk score” is the CHA2DS2–VASc, which gives a point for female sex, alongside factors such as congestive heart failure, hypertension, and diabetes mellitus, and a sliding scale of points for increasing age.
Kotecha pointed out the score was developed before the DOACs were available and may not account for how risk factors have changed in recent decades.
The result is that CHA2DS2–VASc gives the same number of points to an individual with heart failure or prior transient ischemic attack as to a woman aged less than 65 years, “but the magnitude of increased risk is not the same,” Usha Beth Tedrow, MD, Associate Professor of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, said in an interview.
As far back as 2018, it was known that “female sex is a risk modifier, rather than a risk factor for stroke in atrial fibrillation,” noted Jose Joglar, MD, lead author of the 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation said in an interview.
A Danish national registry study involving 239,671 AF patients treated between 1997 and 2015, nearly half of whom were women, showed that, at a CHA2DS2–VASc score of 0, the “risk of stroke between men and women is absolutely the same,” he said.
“It is not until after a CHA2DS2–VASc score of 2 that the curves start to separate,” Joglar, Program Director, Clinical Cardiac Electrophysiology Fellowship Program, The University of Texas Southwestern Medical Center, Dallas, continued, “but by then you have already made the decision to anticoagulate.”
More recently, Kotecha and colleagues conducted a population cohort study of the electronic healthcare records of UK primary care patients treated between 2005 and 2020, and identified 78,852 with AF; more than a third were women.
Their analysis, published on September 1, showed that women had a lower adjusted rate of the primary composite outcome of all-cause mortality, ischemic stroke, or arterial thromboembolism, driven by a reduced mortality rate.
“Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation,” Kotecha and colleagues concluded.
Joglar clarified that “women are at increased risk for stroke than men” overall, but by the time that risk “becomes manifest, other risk factors have come into play, and they have already met the criteria for anticoagulation.”
The authors of the latest ESC guideline therefore concluded that the “inclusion of gender complicates clinical practice both for healthcare professionals and patients.” Their solution was to remove the question of gender for decisions over initiating oral anticoagulant therapy in clinical practice altogether.
This includes individuals who identify as transgender or are undergoing sex hormone therapy, as all the experts interviewed by Medscape Medical News agreed that there is currently insufficient evidence to know if that affects stroke risk.
Instead, guidelines state that the drugs are “recommended in those with a CHA2DS2-VA score of 2 or more and should be considered in those with a CHA2DS2-VA score of 1, following a patient-centered and shared care approach.”
“Dropping the gender part of the risk score is not really a substantial change” from previous ESC or other guidelines, as different points were required in the past to recommend anticoagulants for women and men, Kotecha said, adding that “making the approach easier for clinicians may avoid penalizing women as well as nonbinary and transgender patients.”
Anne B. Curtis, MD, SUNY Distinguished Professor, Department of Medicine, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo in New York, agreed.
Putting aside the question of female sex, she said that there are not a lot of people under the age of 65 years with “absolutely no risk factors,” and so, “if the only reason you would anticoagulate” someone of that age is because they are a woman that “doesn’t make a lot of sense to me.”
The ESC guidelines are “trying to say, ‘look at the other risk factors, and if anything is there, go ahead and anticoagulate,” Curtis said in an interview.
“It’s actually a very thoughtful decision,” Tedrow said, and not “intended to discount risk in women.” Rather, it’s a statement that acknowledges the problem of recommending anticoagulation therapy in women “for whom it is not appropriate.”
Joglar pointed out that that recommendation, although not characterized in the same way, was in fact included in the 2023 US guidelines.
“We wanted to use a more nuanced approach,” he said, and move away from using CHA2DS2–VASc as the prime determinant of whether to start oral anticoagulation and towards a magnitude risk assessment, in which female sex is seen as a risk modifier.
“The Europeans and the Americans are looking at the same data, so we often reach the same conclusions,” Joglar said, although “we sometimes use different wordings.”
Overall, Kotecha expressed the hope that the move “will lead to better implementation of guidelines, at the end of the day.”
“That’s all we can hope for: Patients will be offered a more individualized approach, leading to more appropriate use of treatment in the right patients.”
The newer direct oral anticoagulation is “a much simpler therapy,” he added. “There is very little monitoring, a similar risk of bleeding as aspirin, and yet the ability to largely prevent the high rate of stroke and thromboembolism associated with atrial fibrillation.”
“So, it’s a big ticket item for our communities and public health, particularly as atrial fibrillation is expected to double in prevalence in the next few decades and evidence is building that it can lead to vascular dementia in the long-term.”
No funding was declared. Kotecha declares relationships with Bayer, Protherics Medicines Development, Boston Scientific, Daiichi Sankyo, Boehringer Ingelheim, BMS-Pfizer Alliance, Amomed, MyoKardia. Curtis declared relationships with Janssen Pharmaceuticals, Medtronic, Abbott. Joglar declared no relevant relationships. Tedrow declared no relevant relationships.
A version of this article appeared on Medscape.com.
The European Society of Cardiology (ESC) caused a stir when they recommended in their latest atrial fibrillation (AF) management guideline that gender no longer be included in the decision to initiate oral anticoagulation therapy.
The move aims to level the playing field between men and women and follows a more nuanced understanding of stroke risk in patients with AF, said experts. It also acknowledges the lack of evidence in people receiving cross-sex hormone therapy.
In any case, the guidelines, developed in collaboration with the European Association for Cardio-Thoracic Surgery and published by the European Heart Journal on August 30, simply follow 2023’s US recommendations, they added.
One Size Does Not Fit All
So, what to the ESC guidelines actually say?
They underline that, if left untreated, the risk for ischemic stroke is increased fivefold in patients with AF, and the “default approach should therefore be to provide oral anticoagulation to all eligible AF patients, except those at low risk for incident stroke or thromboembolism.”
However, the authors note that there is a lack of strong evidence on how to apply the current risk scores to help inform that decision in real-world patients.
Dipak Kotecha, MBChB, PhD, Professor of Cardiology at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, England, and senior author of the ESC guidelines, said in an interview that “the available scores have a relatively poor ability to accurately predict which patients will have a stroke or thromboembolic event.”
Instead, he said “a much better approach is for healthcare professionals to look at each patient’s individual risk factors, using the risk scores to identify those patients that might not benefit from oral anticoagulant therapy.”
For these guidelines, the authors therefore wanted to “move away from a one-size-fits-all” approach, Kotecha said, and instead ensure that more patients can benefit from the new range of direct oral anticoagulants (DOACs) that are easier to take and with much lower chance of side effects or major bleeding.
To achieve this, they separated their clinical recommendations from any particular risk score, and instead focused on the practicalities of implementation.
Risk Modifier Vs Risk Factor
To explain their decision the authors highlight that “the most popular risk score” is the CHA2DS2–VASc, which gives a point for female sex, alongside factors such as congestive heart failure, hypertension, and diabetes mellitus, and a sliding scale of points for increasing age.
Kotecha pointed out the score was developed before the DOACs were available and may not account for how risk factors have changed in recent decades.
The result is that CHA2DS2–VASc gives the same number of points to an individual with heart failure or prior transient ischemic attack as to a woman aged less than 65 years, “but the magnitude of increased risk is not the same,” Usha Beth Tedrow, MD, Associate Professor of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, said in an interview.
As far back as 2018, it was known that “female sex is a risk modifier, rather than a risk factor for stroke in atrial fibrillation,” noted Jose Joglar, MD, lead author of the 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation said in an interview.
A Danish national registry study involving 239,671 AF patients treated between 1997 and 2015, nearly half of whom were women, showed that, at a CHA2DS2–VASc score of 0, the “risk of stroke between men and women is absolutely the same,” he said.
“It is not until after a CHA2DS2–VASc score of 2 that the curves start to separate,” Joglar, Program Director, Clinical Cardiac Electrophysiology Fellowship Program, The University of Texas Southwestern Medical Center, Dallas, continued, “but by then you have already made the decision to anticoagulate.”
More recently, Kotecha and colleagues conducted a population cohort study of the electronic healthcare records of UK primary care patients treated between 2005 and 2020, and identified 78,852 with AF; more than a third were women.
Their analysis, published on September 1, showed that women had a lower adjusted rate of the primary composite outcome of all-cause mortality, ischemic stroke, or arterial thromboembolism, driven by a reduced mortality rate.
“Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation,” Kotecha and colleagues concluded.
Joglar clarified that “women are at increased risk for stroke than men” overall, but by the time that risk “becomes manifest, other risk factors have come into play, and they have already met the criteria for anticoagulation.”
The authors of the latest ESC guideline therefore concluded that the “inclusion of gender complicates clinical practice both for healthcare professionals and patients.” Their solution was to remove the question of gender for decisions over initiating oral anticoagulant therapy in clinical practice altogether.
This includes individuals who identify as transgender or are undergoing sex hormone therapy, as all the experts interviewed by Medscape Medical News agreed that there is currently insufficient evidence to know if that affects stroke risk.
Instead, guidelines state that the drugs are “recommended in those with a CHA2DS2-VA score of 2 or more and should be considered in those with a CHA2DS2-VA score of 1, following a patient-centered and shared care approach.”
“Dropping the gender part of the risk score is not really a substantial change” from previous ESC or other guidelines, as different points were required in the past to recommend anticoagulants for women and men, Kotecha said, adding that “making the approach easier for clinicians may avoid penalizing women as well as nonbinary and transgender patients.”
Anne B. Curtis, MD, SUNY Distinguished Professor, Department of Medicine, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo in New York, agreed.
Putting aside the question of female sex, she said that there are not a lot of people under the age of 65 years with “absolutely no risk factors,” and so, “if the only reason you would anticoagulate” someone of that age is because they are a woman that “doesn’t make a lot of sense to me.”
The ESC guidelines are “trying to say, ‘look at the other risk factors, and if anything is there, go ahead and anticoagulate,” Curtis said in an interview.
“It’s actually a very thoughtful decision,” Tedrow said, and not “intended to discount risk in women.” Rather, it’s a statement that acknowledges the problem of recommending anticoagulation therapy in women “for whom it is not appropriate.”
Joglar pointed out that that recommendation, although not characterized in the same way, was in fact included in the 2023 US guidelines.
“We wanted to use a more nuanced approach,” he said, and move away from using CHA2DS2–VASc as the prime determinant of whether to start oral anticoagulation and towards a magnitude risk assessment, in which female sex is seen as a risk modifier.
“The Europeans and the Americans are looking at the same data, so we often reach the same conclusions,” Joglar said, although “we sometimes use different wordings.”
Overall, Kotecha expressed the hope that the move “will lead to better implementation of guidelines, at the end of the day.”
“That’s all we can hope for: Patients will be offered a more individualized approach, leading to more appropriate use of treatment in the right patients.”
The newer direct oral anticoagulation is “a much simpler therapy,” he added. “There is very little monitoring, a similar risk of bleeding as aspirin, and yet the ability to largely prevent the high rate of stroke and thromboembolism associated with atrial fibrillation.”
“So, it’s a big ticket item for our communities and public health, particularly as atrial fibrillation is expected to double in prevalence in the next few decades and evidence is building that it can lead to vascular dementia in the long-term.”
No funding was declared. Kotecha declares relationships with Bayer, Protherics Medicines Development, Boston Scientific, Daiichi Sankyo, Boehringer Ingelheim, BMS-Pfizer Alliance, Amomed, MyoKardia. Curtis declared relationships with Janssen Pharmaceuticals, Medtronic, Abbott. Joglar declared no relevant relationships. Tedrow declared no relevant relationships.
A version of this article appeared on Medscape.com.
The European Society of Cardiology (ESC) caused a stir when they recommended in their latest atrial fibrillation (AF) management guideline that gender no longer be included in the decision to initiate oral anticoagulation therapy.
The move aims to level the playing field between men and women and follows a more nuanced understanding of stroke risk in patients with AF, said experts. It also acknowledges the lack of evidence in people receiving cross-sex hormone therapy.
In any case, the guidelines, developed in collaboration with the European Association for Cardio-Thoracic Surgery and published by the European Heart Journal on August 30, simply follow 2023’s US recommendations, they added.
One Size Does Not Fit All
So, what to the ESC guidelines actually say?
They underline that, if left untreated, the risk for ischemic stroke is increased fivefold in patients with AF, and the “default approach should therefore be to provide oral anticoagulation to all eligible AF patients, except those at low risk for incident stroke or thromboembolism.”
However, the authors note that there is a lack of strong evidence on how to apply the current risk scores to help inform that decision in real-world patients.
Dipak Kotecha, MBChB, PhD, Professor of Cardiology at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, England, and senior author of the ESC guidelines, said in an interview that “the available scores have a relatively poor ability to accurately predict which patients will have a stroke or thromboembolic event.”
Instead, he said “a much better approach is for healthcare professionals to look at each patient’s individual risk factors, using the risk scores to identify those patients that might not benefit from oral anticoagulant therapy.”
For these guidelines, the authors therefore wanted to “move away from a one-size-fits-all” approach, Kotecha said, and instead ensure that more patients can benefit from the new range of direct oral anticoagulants (DOACs) that are easier to take and with much lower chance of side effects or major bleeding.
To achieve this, they separated their clinical recommendations from any particular risk score, and instead focused on the practicalities of implementation.
Risk Modifier Vs Risk Factor
To explain their decision the authors highlight that “the most popular risk score” is the CHA2DS2–VASc, which gives a point for female sex, alongside factors such as congestive heart failure, hypertension, and diabetes mellitus, and a sliding scale of points for increasing age.
Kotecha pointed out the score was developed before the DOACs were available and may not account for how risk factors have changed in recent decades.
The result is that CHA2DS2–VASc gives the same number of points to an individual with heart failure or prior transient ischemic attack as to a woman aged less than 65 years, “but the magnitude of increased risk is not the same,” Usha Beth Tedrow, MD, Associate Professor of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, said in an interview.
As far back as 2018, it was known that “female sex is a risk modifier, rather than a risk factor for stroke in atrial fibrillation,” noted Jose Joglar, MD, lead author of the 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation said in an interview.
A Danish national registry study involving 239,671 AF patients treated between 1997 and 2015, nearly half of whom were women, showed that, at a CHA2DS2–VASc score of 0, the “risk of stroke between men and women is absolutely the same,” he said.
“It is not until after a CHA2DS2–VASc score of 2 that the curves start to separate,” Joglar, Program Director, Clinical Cardiac Electrophysiology Fellowship Program, The University of Texas Southwestern Medical Center, Dallas, continued, “but by then you have already made the decision to anticoagulate.”
More recently, Kotecha and colleagues conducted a population cohort study of the electronic healthcare records of UK primary care patients treated between 2005 and 2020, and identified 78,852 with AF; more than a third were women.
Their analysis, published on September 1, showed that women had a lower adjusted rate of the primary composite outcome of all-cause mortality, ischemic stroke, or arterial thromboembolism, driven by a reduced mortality rate.
“Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation,” Kotecha and colleagues concluded.
Joglar clarified that “women are at increased risk for stroke than men” overall, but by the time that risk “becomes manifest, other risk factors have come into play, and they have already met the criteria for anticoagulation.”
The authors of the latest ESC guideline therefore concluded that the “inclusion of gender complicates clinical practice both for healthcare professionals and patients.” Their solution was to remove the question of gender for decisions over initiating oral anticoagulant therapy in clinical practice altogether.
This includes individuals who identify as transgender or are undergoing sex hormone therapy, as all the experts interviewed by Medscape Medical News agreed that there is currently insufficient evidence to know if that affects stroke risk.
Instead, guidelines state that the drugs are “recommended in those with a CHA2DS2-VA score of 2 or more and should be considered in those with a CHA2DS2-VA score of 1, following a patient-centered and shared care approach.”
“Dropping the gender part of the risk score is not really a substantial change” from previous ESC or other guidelines, as different points were required in the past to recommend anticoagulants for women and men, Kotecha said, adding that “making the approach easier for clinicians may avoid penalizing women as well as nonbinary and transgender patients.”
Anne B. Curtis, MD, SUNY Distinguished Professor, Department of Medicine, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo in New York, agreed.
Putting aside the question of female sex, she said that there are not a lot of people under the age of 65 years with “absolutely no risk factors,” and so, “if the only reason you would anticoagulate” someone of that age is because they are a woman that “doesn’t make a lot of sense to me.”
The ESC guidelines are “trying to say, ‘look at the other risk factors, and if anything is there, go ahead and anticoagulate,” Curtis said in an interview.
“It’s actually a very thoughtful decision,” Tedrow said, and not “intended to discount risk in women.” Rather, it’s a statement that acknowledges the problem of recommending anticoagulation therapy in women “for whom it is not appropriate.”
Joglar pointed out that that recommendation, although not characterized in the same way, was in fact included in the 2023 US guidelines.
“We wanted to use a more nuanced approach,” he said, and move away from using CHA2DS2–VASc as the prime determinant of whether to start oral anticoagulation and towards a magnitude risk assessment, in which female sex is seen as a risk modifier.
“The Europeans and the Americans are looking at the same data, so we often reach the same conclusions,” Joglar said, although “we sometimes use different wordings.”
Overall, Kotecha expressed the hope that the move “will lead to better implementation of guidelines, at the end of the day.”
“That’s all we can hope for: Patients will be offered a more individualized approach, leading to more appropriate use of treatment in the right patients.”
The newer direct oral anticoagulation is “a much simpler therapy,” he added. “There is very little monitoring, a similar risk of bleeding as aspirin, and yet the ability to largely prevent the high rate of stroke and thromboembolism associated with atrial fibrillation.”
“So, it’s a big ticket item for our communities and public health, particularly as atrial fibrillation is expected to double in prevalence in the next few decades and evidence is building that it can lead to vascular dementia in the long-term.”
No funding was declared. Kotecha declares relationships with Bayer, Protherics Medicines Development, Boston Scientific, Daiichi Sankyo, Boehringer Ingelheim, BMS-Pfizer Alliance, Amomed, MyoKardia. Curtis declared relationships with Janssen Pharmaceuticals, Medtronic, Abbott. Joglar declared no relevant relationships. Tedrow declared no relevant relationships.
A version of this article appeared on Medscape.com.
Fall Vaccine Updates From the Advisory Committee on Immunization Practices: New Recommendations
This transcript has been edited for clarity.
This episode of Medicine Matters reviews highlights from the Advisory Committee on Immunization Practices’ (ACIP’s) October 2024 meeting, with new recommendations for pneumococcal, COVID, and meningococcal B (Men B) vaccines, as well as a safety update for maternal RSV vaccination.
Pneumococcal Vaccination and New Lower Age-Based Recommendations
New age-based recommendation. ACIP has lowered the age for routine vaccination with the pneumococcal conjugate vaccine (PCV) from age 65 down to age 50, but only with PCV. Review of data revealed that more than half of those in the 50- to 64-year-old age group already had a risk indication to receive a PCV dose. In addition, rates of invasive pneumococcal disease peak at younger ages in Black patients compared with White patients. The rate of invasive pneumococcal disease (IPD) among Black adults aged 50 or older exceeds the average rate of IPD for all adults aged 65 or older. The goal of this age-based change is to reduce disease in demographic groups with the highest burden of disease.
The new expanded age-based recommendation applies only to vaccination with PCV. Conjugate vaccines trigger memory B-cell production and therefore induce greater long-term immunity. New research is now focusing on higher-valent PCV vaccines. Two 24-valent pneumococcal conjugate vaccines and one 31-valent pneumococcal conjugate vaccine are now in advanced stages of development.
Risk-based recommendation. A risk-based recommendation for ages 19 through 49 years still applies to those with certain medical conditions, including diabetes; chronic heart, lung, liver, or kidney disease; and also for those with immunocompromising conditions. Risk-based recommendations are harder to implement particularly because many vaccines are now administered in pharmacies and pharmacists don’t know the patients as well as their physicians do, so it’s harder for them to know who should get the vaccine if the recommendation is based on risk.
COVID-19 Vaccines With Additional Dose Recommendations
Everyone 6 months or older is recommended to receive a dose of the updated 2024-2025 COVID vaccine. An additional updated COVID vaccine dose is now recommended for everyone aged 65 or older, and for those aged 6 months or older with immunocompromising (moderate or severe) conditions. Review of data revealed that 1 in 6 patients hospitalized with COVID have an immunocompromising condition, and 70% of COVID hospitalizations are in those aged 65 or older. This older age group also has the highest death rates due to COVID-19. We know that vaccination protection wanes with time. Data from previous studies show that additional vaccine doses provide additional protection. Additional doses are now being recommended for those at highest risk.
Timing of additional doses. This second dose is recommended at 6 months after the last updated COVID-19 vaccine dose. However, the additional dose can be given as early as 2 months after the last dose. Those who recently had COVID-19 can wait 3 months before getting an additional vaccine dose. This flexibility allows patients to maximize additional protection by timing additional doses around travel and life events, such as weddings, family get-togethers, or chemotherapy.
Those with immunocompromising conditions may receive more doses. Patients with immunocompromising conditions can receive even more additional doses, if recommended by their physician, under shared clinical decision-making.
Meningococcal Vaccines
Meningococcal disease is rare but deadly. The disease can progress rapidly. As many as 10%-15% of people with meningococcal infection die, even with appropriate antibiotic therapy. And for those who survive, about 20% suffer long-term sequalae (cognitive deficits, hearing loss, limb amputations).
Aligning Men B vaccine dosing intervals. The new ACIP vote applies only to Men B vaccines, of which there are two: one by GSK (brand name Bexsero), and the other by Wyeth, a Pfizer subsidiary (brand name Trumenba). The two MenB vaccine products are not interchangeable. The same type of MenB vaccine has to be used to complete the series.
The MenB vaccines initially had different dosing schedules and now they don’t. ACIP voted to harmonize and align the dosing schedule for the two different MenB products to mirror recent FDA (Food and Drug Administration) labeling updates. So now the dosing recommendations for both MenB vaccines are the same: either two doses given 6 months apart to healthy adolescents and young adults, or a three-dose series given at zero, 1-2 months, and 6 months for those at high risk or for those who want to optimize rapid protection (for example, if they are starting the series within 6 months of going off to college). But understand that the current recommendation for MenB vaccination for healthy adolescents and young adults is based on shared clinical decision-making, preferably for those aged 16-18.
MenACWY. Two doses of MenACWY are routinely recommended, with the first dose at age 11-12 and a second dose at age 16. The MenACWY vaccines are interchangeable.
Implementation challenges and new pentavalent vaccines. Having to use the same MenB vaccine product for all doses in a patient’s series is difficult. It’s even more difficult when the patient needs both MenACWY and MenB vaccinations.
Adding to the complexity is a new pentavalent vaccine from Pfizer (brand name Penbraya) that combines MenACWY with the MenB vaccine. And another pentavalent vaccine version by GSK is up for regulatory decision in February 2025.
The work group did say that they plan to take a fresh look at the meningococcal vaccination schedule. Let’s hope it gets simpler, so more to come on that.
Respiratory Syncytial Virus (RSV) Vaccines
Current RSV vaccine recommendations for older adults. RSV vaccine has both age- and risk-based recommendations. Now, everyone aged 75 or older needs a dose of RSV vaccine. Adults aged 60-75 with risk factors for severe RSV are also recommended to receive a dose of RSV vaccine, but not adults without these risk factors. The conditions associated with increased risk for severe RSV disease include lung disease, heart disease, immune compromise, diabetes, obesity with BMI (body mass index) of 40 or higher, neurologic or neuromuscular conditions, chronic kidney disease, liver disorders, and hematologic disorders. Frailty, as well as living in a nursing home or other long-term care facility, are other risk factors for severe RSV disease. Those aged 60-75 without these risk factors are no longer recommended to receive it.
Three RSV vaccines. We now have three RSV vaccine to choose from. Two are protein subunit vaccines. One is by Pfizer (brand name Abrysvo) that does not contain an adjuvant. The other protein-based RSV vaccine by GSK (brand name Arexvy) does contain an adjuvant. The third RSV vaccine by Moderna (brand name mRESVIA) uses an mRNA platform, and durability of protection is still unclear. However, recent studies now suggest that the RSV protein subunit vaccines confer 36 months of protection rather than only 24 months.
All three RSV vaccines are licensed for those aged 60 or older. The age indication for GSK’s RSV vaccine, Arexvy, has already been lowered by the FDA to age 50. FDA recently lowered the age approval for Abrysvo to age 18 for those at high risk. However, ACIP has not yet expanded its age recommendations for getting these vaccines. One of the main hesitations is vaccine safety concerns. FDA›s safety update presented to ACIP still suggests an increased risk for Guillain-Barré syndrome with both protein-based RSV vaccines among those aged 65 or older. Fortunately, the risk is rare: less than 10 cases per million vaccinations.
RSV immunization for infant protection. RSV season starts in October and goes through March. We now have two new ways to protect babies. One is a maternal RSV vaccine, given at 32-36 weeks of pregnancy to moms who will deliver their babies during RSV season. But only Pfizer’s RSV vaccine (brand name Abrysvo, without an adjuvant) can be given during pregnancy.
A maternal RSV vaccine safety update, presented at ACIP, was reassuring. Abrysvo was not associated with increased risk for preterm birth or small gestational age at birth.
Nirsevimab, a long-acting monoclonal antibody, can be given to infants. Nirsevimab is indicated for all babies under 8 months of age entering their first RSV season.
People who received a maternal RSV vaccine during a previous pregnancy are not recommended to receive additional doses during subsequent pregnancies. However, infants born to women who were vaccinated during a prior pregnancy should receive nirsevimab.
Sandra Adamson Fryhofer, Adjunct Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia, has disclosed conflicts of interest with the American Medical Association, the Medical Association of Atlanta, ACIP, and Medscape.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
This episode of Medicine Matters reviews highlights from the Advisory Committee on Immunization Practices’ (ACIP’s) October 2024 meeting, with new recommendations for pneumococcal, COVID, and meningococcal B (Men B) vaccines, as well as a safety update for maternal RSV vaccination.
Pneumococcal Vaccination and New Lower Age-Based Recommendations
New age-based recommendation. ACIP has lowered the age for routine vaccination with the pneumococcal conjugate vaccine (PCV) from age 65 down to age 50, but only with PCV. Review of data revealed that more than half of those in the 50- to 64-year-old age group already had a risk indication to receive a PCV dose. In addition, rates of invasive pneumococcal disease peak at younger ages in Black patients compared with White patients. The rate of invasive pneumococcal disease (IPD) among Black adults aged 50 or older exceeds the average rate of IPD for all adults aged 65 or older. The goal of this age-based change is to reduce disease in demographic groups with the highest burden of disease.
The new expanded age-based recommendation applies only to vaccination with PCV. Conjugate vaccines trigger memory B-cell production and therefore induce greater long-term immunity. New research is now focusing on higher-valent PCV vaccines. Two 24-valent pneumococcal conjugate vaccines and one 31-valent pneumococcal conjugate vaccine are now in advanced stages of development.
Risk-based recommendation. A risk-based recommendation for ages 19 through 49 years still applies to those with certain medical conditions, including diabetes; chronic heart, lung, liver, or kidney disease; and also for those with immunocompromising conditions. Risk-based recommendations are harder to implement particularly because many vaccines are now administered in pharmacies and pharmacists don’t know the patients as well as their physicians do, so it’s harder for them to know who should get the vaccine if the recommendation is based on risk.
COVID-19 Vaccines With Additional Dose Recommendations
Everyone 6 months or older is recommended to receive a dose of the updated 2024-2025 COVID vaccine. An additional updated COVID vaccine dose is now recommended for everyone aged 65 or older, and for those aged 6 months or older with immunocompromising (moderate or severe) conditions. Review of data revealed that 1 in 6 patients hospitalized with COVID have an immunocompromising condition, and 70% of COVID hospitalizations are in those aged 65 or older. This older age group also has the highest death rates due to COVID-19. We know that vaccination protection wanes with time. Data from previous studies show that additional vaccine doses provide additional protection. Additional doses are now being recommended for those at highest risk.
Timing of additional doses. This second dose is recommended at 6 months after the last updated COVID-19 vaccine dose. However, the additional dose can be given as early as 2 months after the last dose. Those who recently had COVID-19 can wait 3 months before getting an additional vaccine dose. This flexibility allows patients to maximize additional protection by timing additional doses around travel and life events, such as weddings, family get-togethers, or chemotherapy.
Those with immunocompromising conditions may receive more doses. Patients with immunocompromising conditions can receive even more additional doses, if recommended by their physician, under shared clinical decision-making.
Meningococcal Vaccines
Meningococcal disease is rare but deadly. The disease can progress rapidly. As many as 10%-15% of people with meningococcal infection die, even with appropriate antibiotic therapy. And for those who survive, about 20% suffer long-term sequalae (cognitive deficits, hearing loss, limb amputations).
Aligning Men B vaccine dosing intervals. The new ACIP vote applies only to Men B vaccines, of which there are two: one by GSK (brand name Bexsero), and the other by Wyeth, a Pfizer subsidiary (brand name Trumenba). The two MenB vaccine products are not interchangeable. The same type of MenB vaccine has to be used to complete the series.
The MenB vaccines initially had different dosing schedules and now they don’t. ACIP voted to harmonize and align the dosing schedule for the two different MenB products to mirror recent FDA (Food and Drug Administration) labeling updates. So now the dosing recommendations for both MenB vaccines are the same: either two doses given 6 months apart to healthy adolescents and young adults, or a three-dose series given at zero, 1-2 months, and 6 months for those at high risk or for those who want to optimize rapid protection (for example, if they are starting the series within 6 months of going off to college). But understand that the current recommendation for MenB vaccination for healthy adolescents and young adults is based on shared clinical decision-making, preferably for those aged 16-18.
MenACWY. Two doses of MenACWY are routinely recommended, with the first dose at age 11-12 and a second dose at age 16. The MenACWY vaccines are interchangeable.
Implementation challenges and new pentavalent vaccines. Having to use the same MenB vaccine product for all doses in a patient’s series is difficult. It’s even more difficult when the patient needs both MenACWY and MenB vaccinations.
Adding to the complexity is a new pentavalent vaccine from Pfizer (brand name Penbraya) that combines MenACWY with the MenB vaccine. And another pentavalent vaccine version by GSK is up for regulatory decision in February 2025.
The work group did say that they plan to take a fresh look at the meningococcal vaccination schedule. Let’s hope it gets simpler, so more to come on that.
Respiratory Syncytial Virus (RSV) Vaccines
Current RSV vaccine recommendations for older adults. RSV vaccine has both age- and risk-based recommendations. Now, everyone aged 75 or older needs a dose of RSV vaccine. Adults aged 60-75 with risk factors for severe RSV are also recommended to receive a dose of RSV vaccine, but not adults without these risk factors. The conditions associated with increased risk for severe RSV disease include lung disease, heart disease, immune compromise, diabetes, obesity with BMI (body mass index) of 40 or higher, neurologic or neuromuscular conditions, chronic kidney disease, liver disorders, and hematologic disorders. Frailty, as well as living in a nursing home or other long-term care facility, are other risk factors for severe RSV disease. Those aged 60-75 without these risk factors are no longer recommended to receive it.
Three RSV vaccines. We now have three RSV vaccine to choose from. Two are protein subunit vaccines. One is by Pfizer (brand name Abrysvo) that does not contain an adjuvant. The other protein-based RSV vaccine by GSK (brand name Arexvy) does contain an adjuvant. The third RSV vaccine by Moderna (brand name mRESVIA) uses an mRNA platform, and durability of protection is still unclear. However, recent studies now suggest that the RSV protein subunit vaccines confer 36 months of protection rather than only 24 months.
All three RSV vaccines are licensed for those aged 60 or older. The age indication for GSK’s RSV vaccine, Arexvy, has already been lowered by the FDA to age 50. FDA recently lowered the age approval for Abrysvo to age 18 for those at high risk. However, ACIP has not yet expanded its age recommendations for getting these vaccines. One of the main hesitations is vaccine safety concerns. FDA›s safety update presented to ACIP still suggests an increased risk for Guillain-Barré syndrome with both protein-based RSV vaccines among those aged 65 or older. Fortunately, the risk is rare: less than 10 cases per million vaccinations.
RSV immunization for infant protection. RSV season starts in October and goes through March. We now have two new ways to protect babies. One is a maternal RSV vaccine, given at 32-36 weeks of pregnancy to moms who will deliver their babies during RSV season. But only Pfizer’s RSV vaccine (brand name Abrysvo, without an adjuvant) can be given during pregnancy.
A maternal RSV vaccine safety update, presented at ACIP, was reassuring. Abrysvo was not associated with increased risk for preterm birth or small gestational age at birth.
Nirsevimab, a long-acting monoclonal antibody, can be given to infants. Nirsevimab is indicated for all babies under 8 months of age entering their first RSV season.
People who received a maternal RSV vaccine during a previous pregnancy are not recommended to receive additional doses during subsequent pregnancies. However, infants born to women who were vaccinated during a prior pregnancy should receive nirsevimab.
Sandra Adamson Fryhofer, Adjunct Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia, has disclosed conflicts of interest with the American Medical Association, the Medical Association of Atlanta, ACIP, and Medscape.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
This episode of Medicine Matters reviews highlights from the Advisory Committee on Immunization Practices’ (ACIP’s) October 2024 meeting, with new recommendations for pneumococcal, COVID, and meningococcal B (Men B) vaccines, as well as a safety update for maternal RSV vaccination.
Pneumococcal Vaccination and New Lower Age-Based Recommendations
New age-based recommendation. ACIP has lowered the age for routine vaccination with the pneumococcal conjugate vaccine (PCV) from age 65 down to age 50, but only with PCV. Review of data revealed that more than half of those in the 50- to 64-year-old age group already had a risk indication to receive a PCV dose. In addition, rates of invasive pneumococcal disease peak at younger ages in Black patients compared with White patients. The rate of invasive pneumococcal disease (IPD) among Black adults aged 50 or older exceeds the average rate of IPD for all adults aged 65 or older. The goal of this age-based change is to reduce disease in demographic groups with the highest burden of disease.
The new expanded age-based recommendation applies only to vaccination with PCV. Conjugate vaccines trigger memory B-cell production and therefore induce greater long-term immunity. New research is now focusing on higher-valent PCV vaccines. Two 24-valent pneumococcal conjugate vaccines and one 31-valent pneumococcal conjugate vaccine are now in advanced stages of development.
Risk-based recommendation. A risk-based recommendation for ages 19 through 49 years still applies to those with certain medical conditions, including diabetes; chronic heart, lung, liver, or kidney disease; and also for those with immunocompromising conditions. Risk-based recommendations are harder to implement particularly because many vaccines are now administered in pharmacies and pharmacists don’t know the patients as well as their physicians do, so it’s harder for them to know who should get the vaccine if the recommendation is based on risk.
COVID-19 Vaccines With Additional Dose Recommendations
Everyone 6 months or older is recommended to receive a dose of the updated 2024-2025 COVID vaccine. An additional updated COVID vaccine dose is now recommended for everyone aged 65 or older, and for those aged 6 months or older with immunocompromising (moderate or severe) conditions. Review of data revealed that 1 in 6 patients hospitalized with COVID have an immunocompromising condition, and 70% of COVID hospitalizations are in those aged 65 or older. This older age group also has the highest death rates due to COVID-19. We know that vaccination protection wanes with time. Data from previous studies show that additional vaccine doses provide additional protection. Additional doses are now being recommended for those at highest risk.
Timing of additional doses. This second dose is recommended at 6 months after the last updated COVID-19 vaccine dose. However, the additional dose can be given as early as 2 months after the last dose. Those who recently had COVID-19 can wait 3 months before getting an additional vaccine dose. This flexibility allows patients to maximize additional protection by timing additional doses around travel and life events, such as weddings, family get-togethers, or chemotherapy.
Those with immunocompromising conditions may receive more doses. Patients with immunocompromising conditions can receive even more additional doses, if recommended by their physician, under shared clinical decision-making.
Meningococcal Vaccines
Meningococcal disease is rare but deadly. The disease can progress rapidly. As many as 10%-15% of people with meningococcal infection die, even with appropriate antibiotic therapy. And for those who survive, about 20% suffer long-term sequalae (cognitive deficits, hearing loss, limb amputations).
Aligning Men B vaccine dosing intervals. The new ACIP vote applies only to Men B vaccines, of which there are two: one by GSK (brand name Bexsero), and the other by Wyeth, a Pfizer subsidiary (brand name Trumenba). The two MenB vaccine products are not interchangeable. The same type of MenB vaccine has to be used to complete the series.
The MenB vaccines initially had different dosing schedules and now they don’t. ACIP voted to harmonize and align the dosing schedule for the two different MenB products to mirror recent FDA (Food and Drug Administration) labeling updates. So now the dosing recommendations for both MenB vaccines are the same: either two doses given 6 months apart to healthy adolescents and young adults, or a three-dose series given at zero, 1-2 months, and 6 months for those at high risk or for those who want to optimize rapid protection (for example, if they are starting the series within 6 months of going off to college). But understand that the current recommendation for MenB vaccination for healthy adolescents and young adults is based on shared clinical decision-making, preferably for those aged 16-18.
MenACWY. Two doses of MenACWY are routinely recommended, with the first dose at age 11-12 and a second dose at age 16. The MenACWY vaccines are interchangeable.
Implementation challenges and new pentavalent vaccines. Having to use the same MenB vaccine product for all doses in a patient’s series is difficult. It’s even more difficult when the patient needs both MenACWY and MenB vaccinations.
Adding to the complexity is a new pentavalent vaccine from Pfizer (brand name Penbraya) that combines MenACWY with the MenB vaccine. And another pentavalent vaccine version by GSK is up for regulatory decision in February 2025.
The work group did say that they plan to take a fresh look at the meningococcal vaccination schedule. Let’s hope it gets simpler, so more to come on that.
Respiratory Syncytial Virus (RSV) Vaccines
Current RSV vaccine recommendations for older adults. RSV vaccine has both age- and risk-based recommendations. Now, everyone aged 75 or older needs a dose of RSV vaccine. Adults aged 60-75 with risk factors for severe RSV are also recommended to receive a dose of RSV vaccine, but not adults without these risk factors. The conditions associated with increased risk for severe RSV disease include lung disease, heart disease, immune compromise, diabetes, obesity with BMI (body mass index) of 40 or higher, neurologic or neuromuscular conditions, chronic kidney disease, liver disorders, and hematologic disorders. Frailty, as well as living in a nursing home or other long-term care facility, are other risk factors for severe RSV disease. Those aged 60-75 without these risk factors are no longer recommended to receive it.
Three RSV vaccines. We now have three RSV vaccine to choose from. Two are protein subunit vaccines. One is by Pfizer (brand name Abrysvo) that does not contain an adjuvant. The other protein-based RSV vaccine by GSK (brand name Arexvy) does contain an adjuvant. The third RSV vaccine by Moderna (brand name mRESVIA) uses an mRNA platform, and durability of protection is still unclear. However, recent studies now suggest that the RSV protein subunit vaccines confer 36 months of protection rather than only 24 months.
All three RSV vaccines are licensed for those aged 60 or older. The age indication for GSK’s RSV vaccine, Arexvy, has already been lowered by the FDA to age 50. FDA recently lowered the age approval for Abrysvo to age 18 for those at high risk. However, ACIP has not yet expanded its age recommendations for getting these vaccines. One of the main hesitations is vaccine safety concerns. FDA›s safety update presented to ACIP still suggests an increased risk for Guillain-Barré syndrome with both protein-based RSV vaccines among those aged 65 or older. Fortunately, the risk is rare: less than 10 cases per million vaccinations.
RSV immunization for infant protection. RSV season starts in October and goes through March. We now have two new ways to protect babies. One is a maternal RSV vaccine, given at 32-36 weeks of pregnancy to moms who will deliver their babies during RSV season. But only Pfizer’s RSV vaccine (brand name Abrysvo, without an adjuvant) can be given during pregnancy.
A maternal RSV vaccine safety update, presented at ACIP, was reassuring. Abrysvo was not associated with increased risk for preterm birth or small gestational age at birth.
Nirsevimab, a long-acting monoclonal antibody, can be given to infants. Nirsevimab is indicated for all babies under 8 months of age entering their first RSV season.
People who received a maternal RSV vaccine during a previous pregnancy are not recommended to receive additional doses during subsequent pregnancies. However, infants born to women who were vaccinated during a prior pregnancy should receive nirsevimab.
Sandra Adamson Fryhofer, Adjunct Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia, has disclosed conflicts of interest with the American Medical Association, the Medical Association of Atlanta, ACIP, and Medscape.
A version of this article first appeared on Medscape.com.
ASA Releases New Primary Stroke Prevention Guideline
The first update in a decade, the 2024 Guideline for the Primary Prevention of Stroke, replaces the 2014 version and is intended to be a resource for clinicians to help them implement a variety of prevention strategies in patients with no previous history of stroke. It aligns with the American Heart Association’s Life’s Essential 8.
“This guideline is an important and timely update from 2014 for multiple reasons. First, there have been groundbreaking clinical trials that have been published with new medications to not only treat the target disease [including] diabetes/obesity and high cholesterol], but also lower the risk of stroke and heart disease,” said chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
It was published online on October 21 in Stroke.
Up to 80% of Strokes Preventable
Estimates show that every year in the United States, more than 500,000 individuals have a first stroke. However, the guideline authors noted that up to 80% of strokes may be preventable. As a result, they called for better primary stroke prevention that includes improved screening and lifestyle changes.
This includes adoption of the Mediterranean diet, which has been shown to significantly reduce stroke risk, especially when supplemented with consumption of nuts and olive oil.
The guideline recommendations also emphasize the need for physical activity, which is “essential” for cardiovascular health and stroke reduction. The authors underscored this point and provided a new recommendation to screen for sedentary behavior and advise patients to avoid inactivity and engage in regular moderate to vigorous physical activity.
Another new recommendation is based on “robust” data that glucagon-like peptide 1 receptor agonists (GLP-1s) significantly improve the management of type 2 diabetes, weight loss, and lower the risk for cardiovascular disease. As a result, guideline authors called for the use of GLP-1s in patients with diabetes and high cardiovascular risk or established cardiovascular disease.
“The glucagon-like peptide receptor agonists have been shown to not only drastically reduce blood sugars in patients with diabetes, but they also lead to significant weight loss in these patients, which has many downstream benefits. Together, this reduces the risk of stroke and other complications of diabetes,” said Bushnell.
She also noted that another drug class introduced since the 2014 guidelines were published, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven to be highly effective in lowering low-density lipoprotein cholesterol. These medications have also been shown to reduce the risk for stroke.
At Least Two Meds Needed to Reduce BP
Effective blood pressure (BP) management is crucial for stroke prevention. Randomized controlled trials show that a single antihypertensive medication helps only about 30% of participants reach their BP target.
Most patients only achieve the desired BP target with two to three medications. In line with these data, the committee recommends using at least two antihypertensives for primary stroke prevention in most patients who require BP-lowering medications for hypertension.
In patients with antiphospholipid syndrome or systemic lupus erythematosus and no history of stroke or unprovoked venous thromboembolism, the authors recommended antiplatelet therapy to prevent stroke. They added that patients with antiphospholipid syndrome who have had a prior unprovoked venous thrombosis will likely benefit from vitamin K antagonist therapy (target international normalized ratio, 2-3) over direct oral anticoagulants.
Emphasis on Women’s Health
Preventing pregnancy-related stroke is achieved primarily by managing hypertension, the guideline authors noted. They recommended treating verified systolic BP over 160 mm Hg or diastolic BP over 110 mm Hg during pregnancy and up to 6 weeks postpartum to lower the risk for fatal maternal intracerebral hemorrhage.
They noted that adverse pregnancy outcomes are also common and linked to chronic hypertension, which increases stroke risk later in life. Therefore, they recommended screening for these outcomes to assess and manage vascular risk factors. The guideline includes a screening tool to help with this in clinical practice.
Endometriosis, premature ovarian failure (before age 40 years), and early-onset menopause (before age 45 years) are all associated with increased stroke risk. As a result, the guideline authors said screening for all three of these conditions is a “reasonable step in the evaluation and management of vascular risk factors in these individuals to reduce stroke risk.”
Finally, the guideline authors addressed primary stroke prevention in transgender individuals, noting that transgender women undergoing estrogen therapy for gender affirmation are at increased risk. They emphasized that evaluating and modifying risk factors could be beneficial for reducing stroke risk in this patient population.
Challenges Lie Ahead
Now that the guideline has been published, the challenge lies in determining how best to implement “its screening recommendations in primary care and other practices when these clinicians are already pushed to see as many patients as possible,” Bushnell said.
Development of screening tools that can be easily incorporated into the clinic visit or the electronic health record, as well as additional personnel to provide counseling, are probably needed to disseminate them, she added.
Bushnell also emphasized that the guideline includes a strong focus on social determinants of health and related social needs.
“We worked hard to use inclusive language and to consider populations historically excluded from research. In acknowledging that social determinants of health including access to healthcare, access to education, economic stability, neighborhood and geographic location, and social and community context have a tremendous influence on stroke risk, we describe how these factors are closely tied to the prevalence and management of many medical risks like obesity, hypertension, and diabetes.
“Our recommendations offer practical steps for screening and addressing essential health-related social needs, including access to nutritious food, stable housing, and reliable transportation, within clinical practice. By considering these factors more comprehensively, we believe we can make meaningful strides toward reducing the disparities in stroke risk,” said Bushnell.
A version of this article appeared on Medscape.com.
The first update in a decade, the 2024 Guideline for the Primary Prevention of Stroke, replaces the 2014 version and is intended to be a resource for clinicians to help them implement a variety of prevention strategies in patients with no previous history of stroke. It aligns with the American Heart Association’s Life’s Essential 8.
“This guideline is an important and timely update from 2014 for multiple reasons. First, there have been groundbreaking clinical trials that have been published with new medications to not only treat the target disease [including] diabetes/obesity and high cholesterol], but also lower the risk of stroke and heart disease,” said chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
It was published online on October 21 in Stroke.
Up to 80% of Strokes Preventable
Estimates show that every year in the United States, more than 500,000 individuals have a first stroke. However, the guideline authors noted that up to 80% of strokes may be preventable. As a result, they called for better primary stroke prevention that includes improved screening and lifestyle changes.
This includes adoption of the Mediterranean diet, which has been shown to significantly reduce stroke risk, especially when supplemented with consumption of nuts and olive oil.
The guideline recommendations also emphasize the need for physical activity, which is “essential” for cardiovascular health and stroke reduction. The authors underscored this point and provided a new recommendation to screen for sedentary behavior and advise patients to avoid inactivity and engage in regular moderate to vigorous physical activity.
Another new recommendation is based on “robust” data that glucagon-like peptide 1 receptor agonists (GLP-1s) significantly improve the management of type 2 diabetes, weight loss, and lower the risk for cardiovascular disease. As a result, guideline authors called for the use of GLP-1s in patients with diabetes and high cardiovascular risk or established cardiovascular disease.
“The glucagon-like peptide receptor agonists have been shown to not only drastically reduce blood sugars in patients with diabetes, but they also lead to significant weight loss in these patients, which has many downstream benefits. Together, this reduces the risk of stroke and other complications of diabetes,” said Bushnell.
She also noted that another drug class introduced since the 2014 guidelines were published, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven to be highly effective in lowering low-density lipoprotein cholesterol. These medications have also been shown to reduce the risk for stroke.
At Least Two Meds Needed to Reduce BP
Effective blood pressure (BP) management is crucial for stroke prevention. Randomized controlled trials show that a single antihypertensive medication helps only about 30% of participants reach their BP target.
Most patients only achieve the desired BP target with two to three medications. In line with these data, the committee recommends using at least two antihypertensives for primary stroke prevention in most patients who require BP-lowering medications for hypertension.
In patients with antiphospholipid syndrome or systemic lupus erythematosus and no history of stroke or unprovoked venous thromboembolism, the authors recommended antiplatelet therapy to prevent stroke. They added that patients with antiphospholipid syndrome who have had a prior unprovoked venous thrombosis will likely benefit from vitamin K antagonist therapy (target international normalized ratio, 2-3) over direct oral anticoagulants.
Emphasis on Women’s Health
Preventing pregnancy-related stroke is achieved primarily by managing hypertension, the guideline authors noted. They recommended treating verified systolic BP over 160 mm Hg or diastolic BP over 110 mm Hg during pregnancy and up to 6 weeks postpartum to lower the risk for fatal maternal intracerebral hemorrhage.
They noted that adverse pregnancy outcomes are also common and linked to chronic hypertension, which increases stroke risk later in life. Therefore, they recommended screening for these outcomes to assess and manage vascular risk factors. The guideline includes a screening tool to help with this in clinical practice.
Endometriosis, premature ovarian failure (before age 40 years), and early-onset menopause (before age 45 years) are all associated with increased stroke risk. As a result, the guideline authors said screening for all three of these conditions is a “reasonable step in the evaluation and management of vascular risk factors in these individuals to reduce stroke risk.”
Finally, the guideline authors addressed primary stroke prevention in transgender individuals, noting that transgender women undergoing estrogen therapy for gender affirmation are at increased risk. They emphasized that evaluating and modifying risk factors could be beneficial for reducing stroke risk in this patient population.
Challenges Lie Ahead
Now that the guideline has been published, the challenge lies in determining how best to implement “its screening recommendations in primary care and other practices when these clinicians are already pushed to see as many patients as possible,” Bushnell said.
Development of screening tools that can be easily incorporated into the clinic visit or the electronic health record, as well as additional personnel to provide counseling, are probably needed to disseminate them, she added.
Bushnell also emphasized that the guideline includes a strong focus on social determinants of health and related social needs.
“We worked hard to use inclusive language and to consider populations historically excluded from research. In acknowledging that social determinants of health including access to healthcare, access to education, economic stability, neighborhood and geographic location, and social and community context have a tremendous influence on stroke risk, we describe how these factors are closely tied to the prevalence and management of many medical risks like obesity, hypertension, and diabetes.
“Our recommendations offer practical steps for screening and addressing essential health-related social needs, including access to nutritious food, stable housing, and reliable transportation, within clinical practice. By considering these factors more comprehensively, we believe we can make meaningful strides toward reducing the disparities in stroke risk,” said Bushnell.
A version of this article appeared on Medscape.com.
The first update in a decade, the 2024 Guideline for the Primary Prevention of Stroke, replaces the 2014 version and is intended to be a resource for clinicians to help them implement a variety of prevention strategies in patients with no previous history of stroke. It aligns with the American Heart Association’s Life’s Essential 8.
“This guideline is an important and timely update from 2014 for multiple reasons. First, there have been groundbreaking clinical trials that have been published with new medications to not only treat the target disease [including] diabetes/obesity and high cholesterol], but also lower the risk of stroke and heart disease,” said chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
It was published online on October 21 in Stroke.
Up to 80% of Strokes Preventable
Estimates show that every year in the United States, more than 500,000 individuals have a first stroke. However, the guideline authors noted that up to 80% of strokes may be preventable. As a result, they called for better primary stroke prevention that includes improved screening and lifestyle changes.
This includes adoption of the Mediterranean diet, which has been shown to significantly reduce stroke risk, especially when supplemented with consumption of nuts and olive oil.
The guideline recommendations also emphasize the need for physical activity, which is “essential” for cardiovascular health and stroke reduction. The authors underscored this point and provided a new recommendation to screen for sedentary behavior and advise patients to avoid inactivity and engage in regular moderate to vigorous physical activity.
Another new recommendation is based on “robust” data that glucagon-like peptide 1 receptor agonists (GLP-1s) significantly improve the management of type 2 diabetes, weight loss, and lower the risk for cardiovascular disease. As a result, guideline authors called for the use of GLP-1s in patients with diabetes and high cardiovascular risk or established cardiovascular disease.
“The glucagon-like peptide receptor agonists have been shown to not only drastically reduce blood sugars in patients with diabetes, but they also lead to significant weight loss in these patients, which has many downstream benefits. Together, this reduces the risk of stroke and other complications of diabetes,” said Bushnell.
She also noted that another drug class introduced since the 2014 guidelines were published, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven to be highly effective in lowering low-density lipoprotein cholesterol. These medications have also been shown to reduce the risk for stroke.
At Least Two Meds Needed to Reduce BP
Effective blood pressure (BP) management is crucial for stroke prevention. Randomized controlled trials show that a single antihypertensive medication helps only about 30% of participants reach their BP target.
Most patients only achieve the desired BP target with two to three medications. In line with these data, the committee recommends using at least two antihypertensives for primary stroke prevention in most patients who require BP-lowering medications for hypertension.
In patients with antiphospholipid syndrome or systemic lupus erythematosus and no history of stroke or unprovoked venous thromboembolism, the authors recommended antiplatelet therapy to prevent stroke. They added that patients with antiphospholipid syndrome who have had a prior unprovoked venous thrombosis will likely benefit from vitamin K antagonist therapy (target international normalized ratio, 2-3) over direct oral anticoagulants.
Emphasis on Women’s Health
Preventing pregnancy-related stroke is achieved primarily by managing hypertension, the guideline authors noted. They recommended treating verified systolic BP over 160 mm Hg or diastolic BP over 110 mm Hg during pregnancy and up to 6 weeks postpartum to lower the risk for fatal maternal intracerebral hemorrhage.
They noted that adverse pregnancy outcomes are also common and linked to chronic hypertension, which increases stroke risk later in life. Therefore, they recommended screening for these outcomes to assess and manage vascular risk factors. The guideline includes a screening tool to help with this in clinical practice.
Endometriosis, premature ovarian failure (before age 40 years), and early-onset menopause (before age 45 years) are all associated with increased stroke risk. As a result, the guideline authors said screening for all three of these conditions is a “reasonable step in the evaluation and management of vascular risk factors in these individuals to reduce stroke risk.”
Finally, the guideline authors addressed primary stroke prevention in transgender individuals, noting that transgender women undergoing estrogen therapy for gender affirmation are at increased risk. They emphasized that evaluating and modifying risk factors could be beneficial for reducing stroke risk in this patient population.
Challenges Lie Ahead
Now that the guideline has been published, the challenge lies in determining how best to implement “its screening recommendations in primary care and other practices when these clinicians are already pushed to see as many patients as possible,” Bushnell said.
Development of screening tools that can be easily incorporated into the clinic visit or the electronic health record, as well as additional personnel to provide counseling, are probably needed to disseminate them, she added.
Bushnell also emphasized that the guideline includes a strong focus on social determinants of health and related social needs.
“We worked hard to use inclusive language and to consider populations historically excluded from research. In acknowledging that social determinants of health including access to healthcare, access to education, economic stability, neighborhood and geographic location, and social and community context have a tremendous influence on stroke risk, we describe how these factors are closely tied to the prevalence and management of many medical risks like obesity, hypertension, and diabetes.
“Our recommendations offer practical steps for screening and addressing essential health-related social needs, including access to nutritious food, stable housing, and reliable transportation, within clinical practice. By considering these factors more comprehensively, we believe we can make meaningful strides toward reducing the disparities in stroke risk,” said Bushnell.
A version of this article appeared on Medscape.com.
AHS White Paper Guides Treatment of Posttraumatic Headache in Youth
The guidance document, the first of its kind, covers risk factors for prolonged recovery, along with pharmacologic and nonpharmacologic management strategies, and supports an emphasis on multidisciplinary care, lead author Carlyn Patterson Gentile, MD, PhD, attending physician in the Division of Neurology at Children’s Hospital of Philadelphia in Pennsylvania, and colleagues reported.
“There are no guidelines to inform the management of posttraumatic headache in youth, but multiple studies have been conducted over the past 2 decades,” the authors wrote in Headache. “This white paper aims to provide a thorough review of the current literature, identify gaps in knowledge, and provide a road map for [posttraumatic headache] management in youth based on available evidence and expert opinion.”
Clarity for an Underrecognized Issue
According to Russell Lonser, MD, professor and chair of neurological surgery at Ohio State University, Columbus, the white paper is important because it offers concrete guidance for health care providers who may be less familiar with posttraumatic headache in youth.
“It brings together all of the previous literature ... in a very well-written way,” Dr. Lonser said in an interview. “More than anything, it could reassure [providers] that they shouldn’t be hunting down potentially magical cures, and reassure them in symptomatic management.”
Meeryo C. Choe, MD, associate clinical professor of pediatric neurology at UCLA Health in Calabasas, California, said the paper also helps shine a light on what may be a more common condition than the public suspects.
“While the media focuses on the effects of concussion in professional sports athletes, the biggest population of athletes is in our youth population,” Dr. Choe said in a written comment. “Almost 25 million children participate in sports throughout the country, and yet we lack guidelines on how to treat posttraumatic headache which can often develop into persistent postconcussive symptoms.”
This white paper, she noted, builds on Dr. Gentile’s 2021 systematic review, introduces new management recommendations, and aligns with the latest consensus statement from the Concussion in Sport Group.
Risk Factors
The white paper first emphasizes the importance of early identification of youth at high risk for prolonged recovery from posttraumatic headache. Risk factors include female sex, adolescent age, a high number of acute symptoms following the initial injury, and social determinants of health.
“I agree that it is important to identify these patients early to improve the recovery trajectory,” Dr. Choe said.
Identifying these individuals quickly allows for timely intervention with both pharmacologic and nonpharmacologic therapies, Dr. Gentile and colleagues noted, potentially mitigating persistent symptoms. Clinicians are encouraged to perform thorough initial assessments to identify these risk factors and initiate early, personalized management plans.
Initial Management of Acute Posttraumatic Headache
For the initial management of acute posttraumatic headache, the white paper recommends a scheduled dosing regimen of simple analgesics. Ibuprofen at a dosage of 10 mg/kg every 6-8 hours (up to a maximum of 600 mg per dose) combined with acetaminophen has shown the best evidence for efficacy. Provided the patient is clinically stable, this regimen should be initiated within 48 hours of the injury and maintained with scheduled dosing for 3-10 days.
If effective, these medications can subsequently be used on an as-needed basis. Careful usage of analgesics is crucial, the white paper cautions, as overadministration can lead to medication-overuse headaches, complicating the recovery process.
Secondary Treatment Options
In cases where first-line oral medications are ineffective, the AHS white paper outlines several secondary treatment options. These include acute intravenous therapies such as ketorolac, dopamine receptor antagonists, and intravenous fluids. Nerve blocks and oral corticosteroid bridges may also be considered.
The white paper stresses the importance of individualized treatment plans that consider the specific needs and responses of each patient, noting that the evidence supporting these approaches is primarily derived from retrospective studies and case reports.
“Patient preferences should be factored in,” said Sean Rose, MD, pediatric neurologist and codirector of the Complex Concussion Clinic at Nationwide Children’s Hospital, Columbus, Ohio.
Supplements and Preventive Measures
For adolescents and young adults at high risk of prolonged posttraumatic headache, the white paper suggests the use of riboflavin and magnesium supplements. Small randomized clinical trials suggest that these supplements may aid in speeding recovery when administered for 1-2 weeks within 48 hours of injury.
If significant headache persists after 2 weeks, a regimen of riboflavin 400 mg daily and magnesium 400-500 mg nightly can be trialed for 6-8 weeks, in line with recommendations for migraine prevention. Additionally, melatonin at a dose of 3-5 mg nightly for an 8-week course may be considered for patients experiencing comorbid sleep disturbances.
Targeted Preventative Therapy
The white paper emphasizes the importance of targeting preventative therapy to the primary headache phenotype.
For instance, patients presenting with a migraine phenotype, or those with a personal or family history of migraines, may be most likely to respond to medications proven effective in migraine prevention, such as amitriptyline, topiramate, and propranolol.
“Most research evidence [for treating posttraumatic headache in youth] is still based on the treatment of migraine,” Dr. Rose pointed out in a written comment.
Dr. Gentile and colleagues recommend initiating preventive therapies 4-6 weeks post injury if headaches are not improving, occur more than 1-2 days per week, or significantly impact daily functioning.
Specialist Referrals and Physical Activity
Referral to a headache specialist is advised for patients who do not respond to first-line acute and preventive therapies. Specialists can offer advanced diagnostic and therapeutic options, the authors noted, ensuring a comprehensive approach to managing posttraumatic headache.
The white paper also recommends noncontact, sub–symptom threshold aerobic physical activity and activities of daily living after an initial 24-48 hour period of symptom-limited cognitive and physical rest. Engaging in these activities may promote faster recovery and help patients gradually return to their normal routines.
“This has been a shift in the concussion treatment approach over the last decade, and is one of the most important interventions we can recommend as physicians,” Dr. Choe noted. “This is where pediatricians and emergency department physicians seeing children acutely can really make a difference in the recovery trajectory for a child after a concussion. ‘Cocoon therapy’ has been proven not only to not work, but be detrimental to recovery.”
Nonpharmacologic Interventions
Based on clinical assessment, nonpharmacologic interventions may also be considered, according to the white paper. These interventions include cervico-vestibular therapy, which addresses neck and balance issues, and cognitive-behavioral therapy, which helps manage the psychological aspects of chronic headache. Dr. Gentile and colleagues highlighted the potential benefits of a collaborative care model that incorporates these nonpharmacologic interventions alongside pharmacologic treatments, providing a holistic approach to posttraumatic headache management.
“Persisting headaches after concussion are often driven by multiple factors,” Dr. Rose said. “Multidisciplinary concussion clinics can offer multiple treatment approaches such as behavioral, physical therapy, exercise, and medication options.”
Unmet Needs
The white paper concludes by calling for high-quality prospective cohort studies and placebo-controlled, randomized, controlled trials to further advance the understanding and treatment of posttraumatic headache in children.
Dr. Lonser, Dr. Choe, and Dr. Rose all agreed.
“More focused treatment trials are needed to gauge efficacy in children with headache after concussion,” Dr. Rose said.
Specifically, Dr. Gentile and colleagues underscored the need to standardize data collection via common elements, which could improve the ability to compare results across studies and develop more effective treatments. In addition, research into the underlying pathophysiology of posttraumatic headache is crucial for identifying new therapeutic targets and clinical and biological markers that can personalize patient care.
They also stressed the importance of exploring the impact of health disparities and social determinants on posttraumatic headache outcomes, aiming to develop interventions that are equitable and accessible to all patient populations.The white paper was approved by the AHS, and supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke K23 NS124986. The authors disclosed relationships with Eli Lilly, Pfizer, Amgen, and others. The interviewees disclosed no conflicts of interest.
The guidance document, the first of its kind, covers risk factors for prolonged recovery, along with pharmacologic and nonpharmacologic management strategies, and supports an emphasis on multidisciplinary care, lead author Carlyn Patterson Gentile, MD, PhD, attending physician in the Division of Neurology at Children’s Hospital of Philadelphia in Pennsylvania, and colleagues reported.
“There are no guidelines to inform the management of posttraumatic headache in youth, but multiple studies have been conducted over the past 2 decades,” the authors wrote in Headache. “This white paper aims to provide a thorough review of the current literature, identify gaps in knowledge, and provide a road map for [posttraumatic headache] management in youth based on available evidence and expert opinion.”
Clarity for an Underrecognized Issue
According to Russell Lonser, MD, professor and chair of neurological surgery at Ohio State University, Columbus, the white paper is important because it offers concrete guidance for health care providers who may be less familiar with posttraumatic headache in youth.
“It brings together all of the previous literature ... in a very well-written way,” Dr. Lonser said in an interview. “More than anything, it could reassure [providers] that they shouldn’t be hunting down potentially magical cures, and reassure them in symptomatic management.”
Meeryo C. Choe, MD, associate clinical professor of pediatric neurology at UCLA Health in Calabasas, California, said the paper also helps shine a light on what may be a more common condition than the public suspects.
“While the media focuses on the effects of concussion in professional sports athletes, the biggest population of athletes is in our youth population,” Dr. Choe said in a written comment. “Almost 25 million children participate in sports throughout the country, and yet we lack guidelines on how to treat posttraumatic headache which can often develop into persistent postconcussive symptoms.”
This white paper, she noted, builds on Dr. Gentile’s 2021 systematic review, introduces new management recommendations, and aligns with the latest consensus statement from the Concussion in Sport Group.
Risk Factors
The white paper first emphasizes the importance of early identification of youth at high risk for prolonged recovery from posttraumatic headache. Risk factors include female sex, adolescent age, a high number of acute symptoms following the initial injury, and social determinants of health.
“I agree that it is important to identify these patients early to improve the recovery trajectory,” Dr. Choe said.
Identifying these individuals quickly allows for timely intervention with both pharmacologic and nonpharmacologic therapies, Dr. Gentile and colleagues noted, potentially mitigating persistent symptoms. Clinicians are encouraged to perform thorough initial assessments to identify these risk factors and initiate early, personalized management plans.
Initial Management of Acute Posttraumatic Headache
For the initial management of acute posttraumatic headache, the white paper recommends a scheduled dosing regimen of simple analgesics. Ibuprofen at a dosage of 10 mg/kg every 6-8 hours (up to a maximum of 600 mg per dose) combined with acetaminophen has shown the best evidence for efficacy. Provided the patient is clinically stable, this regimen should be initiated within 48 hours of the injury and maintained with scheduled dosing for 3-10 days.
If effective, these medications can subsequently be used on an as-needed basis. Careful usage of analgesics is crucial, the white paper cautions, as overadministration can lead to medication-overuse headaches, complicating the recovery process.
Secondary Treatment Options
In cases where first-line oral medications are ineffective, the AHS white paper outlines several secondary treatment options. These include acute intravenous therapies such as ketorolac, dopamine receptor antagonists, and intravenous fluids. Nerve blocks and oral corticosteroid bridges may also be considered.
The white paper stresses the importance of individualized treatment plans that consider the specific needs and responses of each patient, noting that the evidence supporting these approaches is primarily derived from retrospective studies and case reports.
“Patient preferences should be factored in,” said Sean Rose, MD, pediatric neurologist and codirector of the Complex Concussion Clinic at Nationwide Children’s Hospital, Columbus, Ohio.
Supplements and Preventive Measures
For adolescents and young adults at high risk of prolonged posttraumatic headache, the white paper suggests the use of riboflavin and magnesium supplements. Small randomized clinical trials suggest that these supplements may aid in speeding recovery when administered for 1-2 weeks within 48 hours of injury.
If significant headache persists after 2 weeks, a regimen of riboflavin 400 mg daily and magnesium 400-500 mg nightly can be trialed for 6-8 weeks, in line with recommendations for migraine prevention. Additionally, melatonin at a dose of 3-5 mg nightly for an 8-week course may be considered for patients experiencing comorbid sleep disturbances.
Targeted Preventative Therapy
The white paper emphasizes the importance of targeting preventative therapy to the primary headache phenotype.
For instance, patients presenting with a migraine phenotype, or those with a personal or family history of migraines, may be most likely to respond to medications proven effective in migraine prevention, such as amitriptyline, topiramate, and propranolol.
“Most research evidence [for treating posttraumatic headache in youth] is still based on the treatment of migraine,” Dr. Rose pointed out in a written comment.
Dr. Gentile and colleagues recommend initiating preventive therapies 4-6 weeks post injury if headaches are not improving, occur more than 1-2 days per week, or significantly impact daily functioning.
Specialist Referrals and Physical Activity
Referral to a headache specialist is advised for patients who do not respond to first-line acute and preventive therapies. Specialists can offer advanced diagnostic and therapeutic options, the authors noted, ensuring a comprehensive approach to managing posttraumatic headache.
The white paper also recommends noncontact, sub–symptom threshold aerobic physical activity and activities of daily living after an initial 24-48 hour period of symptom-limited cognitive and physical rest. Engaging in these activities may promote faster recovery and help patients gradually return to their normal routines.
“This has been a shift in the concussion treatment approach over the last decade, and is one of the most important interventions we can recommend as physicians,” Dr. Choe noted. “This is where pediatricians and emergency department physicians seeing children acutely can really make a difference in the recovery trajectory for a child after a concussion. ‘Cocoon therapy’ has been proven not only to not work, but be detrimental to recovery.”
Nonpharmacologic Interventions
Based on clinical assessment, nonpharmacologic interventions may also be considered, according to the white paper. These interventions include cervico-vestibular therapy, which addresses neck and balance issues, and cognitive-behavioral therapy, which helps manage the psychological aspects of chronic headache. Dr. Gentile and colleagues highlighted the potential benefits of a collaborative care model that incorporates these nonpharmacologic interventions alongside pharmacologic treatments, providing a holistic approach to posttraumatic headache management.
“Persisting headaches after concussion are often driven by multiple factors,” Dr. Rose said. “Multidisciplinary concussion clinics can offer multiple treatment approaches such as behavioral, physical therapy, exercise, and medication options.”
Unmet Needs
The white paper concludes by calling for high-quality prospective cohort studies and placebo-controlled, randomized, controlled trials to further advance the understanding and treatment of posttraumatic headache in children.
Dr. Lonser, Dr. Choe, and Dr. Rose all agreed.
“More focused treatment trials are needed to gauge efficacy in children with headache after concussion,” Dr. Rose said.
Specifically, Dr. Gentile and colleagues underscored the need to standardize data collection via common elements, which could improve the ability to compare results across studies and develop more effective treatments. In addition, research into the underlying pathophysiology of posttraumatic headache is crucial for identifying new therapeutic targets and clinical and biological markers that can personalize patient care.
They also stressed the importance of exploring the impact of health disparities and social determinants on posttraumatic headache outcomes, aiming to develop interventions that are equitable and accessible to all patient populations.The white paper was approved by the AHS, and supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke K23 NS124986. The authors disclosed relationships with Eli Lilly, Pfizer, Amgen, and others. The interviewees disclosed no conflicts of interest.
The guidance document, the first of its kind, covers risk factors for prolonged recovery, along with pharmacologic and nonpharmacologic management strategies, and supports an emphasis on multidisciplinary care, lead author Carlyn Patterson Gentile, MD, PhD, attending physician in the Division of Neurology at Children’s Hospital of Philadelphia in Pennsylvania, and colleagues reported.
“There are no guidelines to inform the management of posttraumatic headache in youth, but multiple studies have been conducted over the past 2 decades,” the authors wrote in Headache. “This white paper aims to provide a thorough review of the current literature, identify gaps in knowledge, and provide a road map for [posttraumatic headache] management in youth based on available evidence and expert opinion.”
Clarity for an Underrecognized Issue
According to Russell Lonser, MD, professor and chair of neurological surgery at Ohio State University, Columbus, the white paper is important because it offers concrete guidance for health care providers who may be less familiar with posttraumatic headache in youth.
“It brings together all of the previous literature ... in a very well-written way,” Dr. Lonser said in an interview. “More than anything, it could reassure [providers] that they shouldn’t be hunting down potentially magical cures, and reassure them in symptomatic management.”
Meeryo C. Choe, MD, associate clinical professor of pediatric neurology at UCLA Health in Calabasas, California, said the paper also helps shine a light on what may be a more common condition than the public suspects.
“While the media focuses on the effects of concussion in professional sports athletes, the biggest population of athletes is in our youth population,” Dr. Choe said in a written comment. “Almost 25 million children participate in sports throughout the country, and yet we lack guidelines on how to treat posttraumatic headache which can often develop into persistent postconcussive symptoms.”
This white paper, she noted, builds on Dr. Gentile’s 2021 systematic review, introduces new management recommendations, and aligns with the latest consensus statement from the Concussion in Sport Group.
Risk Factors
The white paper first emphasizes the importance of early identification of youth at high risk for prolonged recovery from posttraumatic headache. Risk factors include female sex, adolescent age, a high number of acute symptoms following the initial injury, and social determinants of health.
“I agree that it is important to identify these patients early to improve the recovery trajectory,” Dr. Choe said.
Identifying these individuals quickly allows for timely intervention with both pharmacologic and nonpharmacologic therapies, Dr. Gentile and colleagues noted, potentially mitigating persistent symptoms. Clinicians are encouraged to perform thorough initial assessments to identify these risk factors and initiate early, personalized management plans.
Initial Management of Acute Posttraumatic Headache
For the initial management of acute posttraumatic headache, the white paper recommends a scheduled dosing regimen of simple analgesics. Ibuprofen at a dosage of 10 mg/kg every 6-8 hours (up to a maximum of 600 mg per dose) combined with acetaminophen has shown the best evidence for efficacy. Provided the patient is clinically stable, this regimen should be initiated within 48 hours of the injury and maintained with scheduled dosing for 3-10 days.
If effective, these medications can subsequently be used on an as-needed basis. Careful usage of analgesics is crucial, the white paper cautions, as overadministration can lead to medication-overuse headaches, complicating the recovery process.
Secondary Treatment Options
In cases where first-line oral medications are ineffective, the AHS white paper outlines several secondary treatment options. These include acute intravenous therapies such as ketorolac, dopamine receptor antagonists, and intravenous fluids. Nerve blocks and oral corticosteroid bridges may also be considered.
The white paper stresses the importance of individualized treatment plans that consider the specific needs and responses of each patient, noting that the evidence supporting these approaches is primarily derived from retrospective studies and case reports.
“Patient preferences should be factored in,” said Sean Rose, MD, pediatric neurologist and codirector of the Complex Concussion Clinic at Nationwide Children’s Hospital, Columbus, Ohio.
Supplements and Preventive Measures
For adolescents and young adults at high risk of prolonged posttraumatic headache, the white paper suggests the use of riboflavin and magnesium supplements. Small randomized clinical trials suggest that these supplements may aid in speeding recovery when administered for 1-2 weeks within 48 hours of injury.
If significant headache persists after 2 weeks, a regimen of riboflavin 400 mg daily and magnesium 400-500 mg nightly can be trialed for 6-8 weeks, in line with recommendations for migraine prevention. Additionally, melatonin at a dose of 3-5 mg nightly for an 8-week course may be considered for patients experiencing comorbid sleep disturbances.
Targeted Preventative Therapy
The white paper emphasizes the importance of targeting preventative therapy to the primary headache phenotype.
For instance, patients presenting with a migraine phenotype, or those with a personal or family history of migraines, may be most likely to respond to medications proven effective in migraine prevention, such as amitriptyline, topiramate, and propranolol.
“Most research evidence [for treating posttraumatic headache in youth] is still based on the treatment of migraine,” Dr. Rose pointed out in a written comment.
Dr. Gentile and colleagues recommend initiating preventive therapies 4-6 weeks post injury if headaches are not improving, occur more than 1-2 days per week, or significantly impact daily functioning.
Specialist Referrals and Physical Activity
Referral to a headache specialist is advised for patients who do not respond to first-line acute and preventive therapies. Specialists can offer advanced diagnostic and therapeutic options, the authors noted, ensuring a comprehensive approach to managing posttraumatic headache.
The white paper also recommends noncontact, sub–symptom threshold aerobic physical activity and activities of daily living after an initial 24-48 hour period of symptom-limited cognitive and physical rest. Engaging in these activities may promote faster recovery and help patients gradually return to their normal routines.
“This has been a shift in the concussion treatment approach over the last decade, and is one of the most important interventions we can recommend as physicians,” Dr. Choe noted. “This is where pediatricians and emergency department physicians seeing children acutely can really make a difference in the recovery trajectory for a child after a concussion. ‘Cocoon therapy’ has been proven not only to not work, but be detrimental to recovery.”
Nonpharmacologic Interventions
Based on clinical assessment, nonpharmacologic interventions may also be considered, according to the white paper. These interventions include cervico-vestibular therapy, which addresses neck and balance issues, and cognitive-behavioral therapy, which helps manage the psychological aspects of chronic headache. Dr. Gentile and colleagues highlighted the potential benefits of a collaborative care model that incorporates these nonpharmacologic interventions alongside pharmacologic treatments, providing a holistic approach to posttraumatic headache management.
“Persisting headaches after concussion are often driven by multiple factors,” Dr. Rose said. “Multidisciplinary concussion clinics can offer multiple treatment approaches such as behavioral, physical therapy, exercise, and medication options.”
Unmet Needs
The white paper concludes by calling for high-quality prospective cohort studies and placebo-controlled, randomized, controlled trials to further advance the understanding and treatment of posttraumatic headache in children.
Dr. Lonser, Dr. Choe, and Dr. Rose all agreed.
“More focused treatment trials are needed to gauge efficacy in children with headache after concussion,” Dr. Rose said.
Specifically, Dr. Gentile and colleagues underscored the need to standardize data collection via common elements, which could improve the ability to compare results across studies and develop more effective treatments. In addition, research into the underlying pathophysiology of posttraumatic headache is crucial for identifying new therapeutic targets and clinical and biological markers that can personalize patient care.
They also stressed the importance of exploring the impact of health disparities and social determinants on posttraumatic headache outcomes, aiming to develop interventions that are equitable and accessible to all patient populations.The white paper was approved by the AHS, and supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke K23 NS124986. The authors disclosed relationships with Eli Lilly, Pfizer, Amgen, and others. The interviewees disclosed no conflicts of interest.
FROM HEADACHE
New Guidance on Genetic Testing for Kidney Disease
A new consensus statement recommended genetic testing for all categories of kidney diseases whenever a genetic cause is suspected and offered guidance on who to test, which tests are the most useful, and how to talk to patients about results.
The statement, published online in the American Journal of Kidney Diseases, is the work of four dozen authors — including patients, nephrologists, experts in clinical and laboratory genetics, kidney pathology, genetic counseling, and ethics. The experts were brought together by the National Kidney Foundation (NKF) with the goal of broadening use and understanding of the tests.
About 10% or more of kidney diseases in adults and 70% of selected chronic kidney diseases (CKDs) in children have genetic causes. But nephrologists have reported a lack of education about genetic testing, and other barriers to wider use, including limited access to testing, cost, insurance coverage, and a small number of genetic counselors who are versed in kidney genetics.
Genetic testing “in the kidney field is a little less developed than in other fields,” said co–lead author Nora Franceschini, MD, MPH, a professor of epidemiology at the University of North Carolina Gillings School of Global Public Health, Chapel Hill, and a nephrologist who studies the genetic epidemiology of hypertension and kidney and cardiovascular diseases.
There are already many known variants that play a role in various kidney diseases and more are on the horizon, Dr. Franceschini told this news organization. More genetic tests will be available in the near future. “The workforce needs to be prepared,” she said.
The statement is an initial step that gets clinicians thinking about testing in a more systematic way, said Dr. Franceschini. “Genetic testing is just another test that physicians can use to complete the story when evaluating patients.
“I think clinicians are ready to implement” testing, said Dr. Franceschini. “We just need to have better guidance.”
Who, When, What to Test
The NKF statement is not the first to try to address gaps in use and knowledge. A European Renal Association Working Group published guidelines in 2022.
The NKF Working Group came up with 56 recommendations and separate algorithms to guide testing for adult and pediatric individuals who are considered at-risk (and currently asymptomatic) and for those who already have clinical disease.
Testing can help determine a cause if there’s an atypical clinical presentation, and it can help avoid biopsies, said the group. Tests can also guide choice of therapy.
For at-risk individuals, there are two broad situations in which testing might be considered: In family members of a patient who already has kidney disease and in potential kidney donors. But testing at-risk children younger than 18 years should only be done if there is an intervention available that could prevent, treat, or slow progression of disease, said the authors.
For patients with an established genetic diagnosis, at-risk family members should be tested with the known single-gene variant diagnostic instead of a broad panel, said the group.
Single-gene variant testing is most appropriate in situations when clinical disease is already evident or when there is known genetic disease in the family, according to the NKF panel. A large diagnostic panel that covers the many common genetic causes of kidney disease is recommended for the majority of patients.
The group recommended that apolipoprotein L1 (APOL1) testing should be included in gene panels for CKD, and it should be offered to any patient “with clinical findings suggestive of APOL1-association nephropathy, regardless of race and ethnicity.”
High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and are found in one out of seven individuals of African ancestry, which means the focus has largely been on testing those with that ancestry.
However, with many unknowns about APOL1, the NKF panel did not want to “profile” individuals and suggest that testing should not be based on skin color or race/ethnicity, said Dr. Franceschini.
In addition, only about 10% of those with the variant develop disease, so testing is not currently warranted for those who do not already have kidney disease, said the group.
They also recommended against the use of polygenic risk scores, saying that there are not enough data from diverse populations in genome-wide association studies for kidney disease or on their clinical utility.
More Education Needed; Many Barriers
The authors acknowledged that nephrologists generally receive little education in genetics and lack support for interpreting and discussing results.
“Nephrologists should be provided with training and best practice resources to interpret genetic testing and discuss the results with individuals and their families,” they wrote, adding that there’s a need for genomic medicine boards at academic centers that would be available to help nephrologists interpret results and plot clinical management.
The group did not, however, cite some of the other barriers to adoption of testing, including a limited number of sites offering testing, cost, and lack of insurance coverage for the diagnostics.
Medicare may cover genetic testing for kidney disease when an individual has symptoms and there is a Food and Drug Administration–approved test. Joseph Vassalotti, MD, chief medical officer for the NKF, said private insurance may cover the testing if the nephrologist deems it medically necessary, but that he usually confirms coverage before initiating testing. The often-used Renasight panel, which tests for 385 genes related to kidney diseases, costs $300-$400 out of pocket, Dr. Vassalotti told this news organization.
In a survey of 149 nephrologists conducted in 2021, both users (46%) and nonusers of the tests (69%) said that high cost was the most significant perceived barrier to implementing widespread testing. A third of users and almost two thirds of nonusers said that poor availability or lack of ease of testing was the second most significant barrier.
Clinics that test for kidney genes “are largely confined to large academic centers and some specialty clinics,” said Dominic Raj, MD, the Bert B. Brooks chair, and Divya Shankaranarayanan, MD, director of the Kidney Precision Medicine Clinic, both at George Washington University School of Medicine & Health Sciences, Washington, DC, in an email.
Testing is also limited by cultural barriers, lack of genetic literacy, and patients’ concerns that a positive result could lead to a loss of health insurance coverage, said Dr. Raj and Dr. Shankaranarayanan.
Paper Will Help Expand Use
A lack of consensus has also held back expansion. The new statement “may lead to increased and possibly judicious utilization of genetic testing in nephrology practices,” said Dr. Raj and Dr. Shankaranarayanan. “Most importantly, the panel has given specific guidance as to what type of genetic test platform is likely to yield the best and most cost-effective yield.”
The most effective use is “in monogenic kidney diseases and to a lesser extent in oligogenic kidney disease,” said Dr. Raj and Dr. Shankaranarayanan, adding that testing is of less-certain utility in polygenic kidney diseases, “where complex genetic and epigenetic factors determine the phenotype.”
Genetic testing might be especially useful “in atypical clinical presentations” and can help clinicians avoid unnecessary expensive and extensive investigations when multiple organ systems are involved, they said.
“Most importantly, [testing] might prevent unnecessary and potentially harmful treatment and enable targeted specific treatment, when available,” said Dr. Raj and Dr. Shankaranarayanan.
Dr. Franceschini and Dr. Shankaranarayanan reported no relevant financial relationships. Dr. Raj disclosed that he received consulting fees and honoraria from Novo Nordisk and is a national leader for the company’s Zeus trial, studying whether ziltivekimab reduces the risk for cardiovascular events in cardiovascular disease, CKD, and inflammation. He also participated in a study of Natera’s Renasight, a 385-gene panel for kidney disease.
A version of this article first appeared on Medscape.com.
A new consensus statement recommended genetic testing for all categories of kidney diseases whenever a genetic cause is suspected and offered guidance on who to test, which tests are the most useful, and how to talk to patients about results.
The statement, published online in the American Journal of Kidney Diseases, is the work of four dozen authors — including patients, nephrologists, experts in clinical and laboratory genetics, kidney pathology, genetic counseling, and ethics. The experts were brought together by the National Kidney Foundation (NKF) with the goal of broadening use and understanding of the tests.
About 10% or more of kidney diseases in adults and 70% of selected chronic kidney diseases (CKDs) in children have genetic causes. But nephrologists have reported a lack of education about genetic testing, and other barriers to wider use, including limited access to testing, cost, insurance coverage, and a small number of genetic counselors who are versed in kidney genetics.
Genetic testing “in the kidney field is a little less developed than in other fields,” said co–lead author Nora Franceschini, MD, MPH, a professor of epidemiology at the University of North Carolina Gillings School of Global Public Health, Chapel Hill, and a nephrologist who studies the genetic epidemiology of hypertension and kidney and cardiovascular diseases.
There are already many known variants that play a role in various kidney diseases and more are on the horizon, Dr. Franceschini told this news organization. More genetic tests will be available in the near future. “The workforce needs to be prepared,” she said.
The statement is an initial step that gets clinicians thinking about testing in a more systematic way, said Dr. Franceschini. “Genetic testing is just another test that physicians can use to complete the story when evaluating patients.
“I think clinicians are ready to implement” testing, said Dr. Franceschini. “We just need to have better guidance.”
Who, When, What to Test
The NKF statement is not the first to try to address gaps in use and knowledge. A European Renal Association Working Group published guidelines in 2022.
The NKF Working Group came up with 56 recommendations and separate algorithms to guide testing for adult and pediatric individuals who are considered at-risk (and currently asymptomatic) and for those who already have clinical disease.
Testing can help determine a cause if there’s an atypical clinical presentation, and it can help avoid biopsies, said the group. Tests can also guide choice of therapy.
For at-risk individuals, there are two broad situations in which testing might be considered: In family members of a patient who already has kidney disease and in potential kidney donors. But testing at-risk children younger than 18 years should only be done if there is an intervention available that could prevent, treat, or slow progression of disease, said the authors.
For patients with an established genetic diagnosis, at-risk family members should be tested with the known single-gene variant diagnostic instead of a broad panel, said the group.
Single-gene variant testing is most appropriate in situations when clinical disease is already evident or when there is known genetic disease in the family, according to the NKF panel. A large diagnostic panel that covers the many common genetic causes of kidney disease is recommended for the majority of patients.
The group recommended that apolipoprotein L1 (APOL1) testing should be included in gene panels for CKD, and it should be offered to any patient “with clinical findings suggestive of APOL1-association nephropathy, regardless of race and ethnicity.”
High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and are found in one out of seven individuals of African ancestry, which means the focus has largely been on testing those with that ancestry.
However, with many unknowns about APOL1, the NKF panel did not want to “profile” individuals and suggest that testing should not be based on skin color or race/ethnicity, said Dr. Franceschini.
In addition, only about 10% of those with the variant develop disease, so testing is not currently warranted for those who do not already have kidney disease, said the group.
They also recommended against the use of polygenic risk scores, saying that there are not enough data from diverse populations in genome-wide association studies for kidney disease or on their clinical utility.
More Education Needed; Many Barriers
The authors acknowledged that nephrologists generally receive little education in genetics and lack support for interpreting and discussing results.
“Nephrologists should be provided with training and best practice resources to interpret genetic testing and discuss the results with individuals and their families,” they wrote, adding that there’s a need for genomic medicine boards at academic centers that would be available to help nephrologists interpret results and plot clinical management.
The group did not, however, cite some of the other barriers to adoption of testing, including a limited number of sites offering testing, cost, and lack of insurance coverage for the diagnostics.
Medicare may cover genetic testing for kidney disease when an individual has symptoms and there is a Food and Drug Administration–approved test. Joseph Vassalotti, MD, chief medical officer for the NKF, said private insurance may cover the testing if the nephrologist deems it medically necessary, but that he usually confirms coverage before initiating testing. The often-used Renasight panel, which tests for 385 genes related to kidney diseases, costs $300-$400 out of pocket, Dr. Vassalotti told this news organization.
In a survey of 149 nephrologists conducted in 2021, both users (46%) and nonusers of the tests (69%) said that high cost was the most significant perceived barrier to implementing widespread testing. A third of users and almost two thirds of nonusers said that poor availability or lack of ease of testing was the second most significant barrier.
Clinics that test for kidney genes “are largely confined to large academic centers and some specialty clinics,” said Dominic Raj, MD, the Bert B. Brooks chair, and Divya Shankaranarayanan, MD, director of the Kidney Precision Medicine Clinic, both at George Washington University School of Medicine & Health Sciences, Washington, DC, in an email.
Testing is also limited by cultural barriers, lack of genetic literacy, and patients’ concerns that a positive result could lead to a loss of health insurance coverage, said Dr. Raj and Dr. Shankaranarayanan.
Paper Will Help Expand Use
A lack of consensus has also held back expansion. The new statement “may lead to increased and possibly judicious utilization of genetic testing in nephrology practices,” said Dr. Raj and Dr. Shankaranarayanan. “Most importantly, the panel has given specific guidance as to what type of genetic test platform is likely to yield the best and most cost-effective yield.”
The most effective use is “in monogenic kidney diseases and to a lesser extent in oligogenic kidney disease,” said Dr. Raj and Dr. Shankaranarayanan, adding that testing is of less-certain utility in polygenic kidney diseases, “where complex genetic and epigenetic factors determine the phenotype.”
Genetic testing might be especially useful “in atypical clinical presentations” and can help clinicians avoid unnecessary expensive and extensive investigations when multiple organ systems are involved, they said.
“Most importantly, [testing] might prevent unnecessary and potentially harmful treatment and enable targeted specific treatment, when available,” said Dr. Raj and Dr. Shankaranarayanan.
Dr. Franceschini and Dr. Shankaranarayanan reported no relevant financial relationships. Dr. Raj disclosed that he received consulting fees and honoraria from Novo Nordisk and is a national leader for the company’s Zeus trial, studying whether ziltivekimab reduces the risk for cardiovascular events in cardiovascular disease, CKD, and inflammation. He also participated in a study of Natera’s Renasight, a 385-gene panel for kidney disease.
A version of this article first appeared on Medscape.com.
A new consensus statement recommended genetic testing for all categories of kidney diseases whenever a genetic cause is suspected and offered guidance on who to test, which tests are the most useful, and how to talk to patients about results.
The statement, published online in the American Journal of Kidney Diseases, is the work of four dozen authors — including patients, nephrologists, experts in clinical and laboratory genetics, kidney pathology, genetic counseling, and ethics. The experts were brought together by the National Kidney Foundation (NKF) with the goal of broadening use and understanding of the tests.
About 10% or more of kidney diseases in adults and 70% of selected chronic kidney diseases (CKDs) in children have genetic causes. But nephrologists have reported a lack of education about genetic testing, and other barriers to wider use, including limited access to testing, cost, insurance coverage, and a small number of genetic counselors who are versed in kidney genetics.
Genetic testing “in the kidney field is a little less developed than in other fields,” said co–lead author Nora Franceschini, MD, MPH, a professor of epidemiology at the University of North Carolina Gillings School of Global Public Health, Chapel Hill, and a nephrologist who studies the genetic epidemiology of hypertension and kidney and cardiovascular diseases.
There are already many known variants that play a role in various kidney diseases and more are on the horizon, Dr. Franceschini told this news organization. More genetic tests will be available in the near future. “The workforce needs to be prepared,” she said.
The statement is an initial step that gets clinicians thinking about testing in a more systematic way, said Dr. Franceschini. “Genetic testing is just another test that physicians can use to complete the story when evaluating patients.
“I think clinicians are ready to implement” testing, said Dr. Franceschini. “We just need to have better guidance.”
Who, When, What to Test
The NKF statement is not the first to try to address gaps in use and knowledge. A European Renal Association Working Group published guidelines in 2022.
The NKF Working Group came up with 56 recommendations and separate algorithms to guide testing for adult and pediatric individuals who are considered at-risk (and currently asymptomatic) and for those who already have clinical disease.
Testing can help determine a cause if there’s an atypical clinical presentation, and it can help avoid biopsies, said the group. Tests can also guide choice of therapy.
For at-risk individuals, there are two broad situations in which testing might be considered: In family members of a patient who already has kidney disease and in potential kidney donors. But testing at-risk children younger than 18 years should only be done if there is an intervention available that could prevent, treat, or slow progression of disease, said the authors.
For patients with an established genetic diagnosis, at-risk family members should be tested with the known single-gene variant diagnostic instead of a broad panel, said the group.
Single-gene variant testing is most appropriate in situations when clinical disease is already evident or when there is known genetic disease in the family, according to the NKF panel. A large diagnostic panel that covers the many common genetic causes of kidney disease is recommended for the majority of patients.
The group recommended that apolipoprotein L1 (APOL1) testing should be included in gene panels for CKD, and it should be offered to any patient “with clinical findings suggestive of APOL1-association nephropathy, regardless of race and ethnicity.”
High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and are found in one out of seven individuals of African ancestry, which means the focus has largely been on testing those with that ancestry.
However, with many unknowns about APOL1, the NKF panel did not want to “profile” individuals and suggest that testing should not be based on skin color or race/ethnicity, said Dr. Franceschini.
In addition, only about 10% of those with the variant develop disease, so testing is not currently warranted for those who do not already have kidney disease, said the group.
They also recommended against the use of polygenic risk scores, saying that there are not enough data from diverse populations in genome-wide association studies for kidney disease or on their clinical utility.
More Education Needed; Many Barriers
The authors acknowledged that nephrologists generally receive little education in genetics and lack support for interpreting and discussing results.
“Nephrologists should be provided with training and best practice resources to interpret genetic testing and discuss the results with individuals and their families,” they wrote, adding that there’s a need for genomic medicine boards at academic centers that would be available to help nephrologists interpret results and plot clinical management.
The group did not, however, cite some of the other barriers to adoption of testing, including a limited number of sites offering testing, cost, and lack of insurance coverage for the diagnostics.
Medicare may cover genetic testing for kidney disease when an individual has symptoms and there is a Food and Drug Administration–approved test. Joseph Vassalotti, MD, chief medical officer for the NKF, said private insurance may cover the testing if the nephrologist deems it medically necessary, but that he usually confirms coverage before initiating testing. The often-used Renasight panel, which tests for 385 genes related to kidney diseases, costs $300-$400 out of pocket, Dr. Vassalotti told this news organization.
In a survey of 149 nephrologists conducted in 2021, both users (46%) and nonusers of the tests (69%) said that high cost was the most significant perceived barrier to implementing widespread testing. A third of users and almost two thirds of nonusers said that poor availability or lack of ease of testing was the second most significant barrier.
Clinics that test for kidney genes “are largely confined to large academic centers and some specialty clinics,” said Dominic Raj, MD, the Bert B. Brooks chair, and Divya Shankaranarayanan, MD, director of the Kidney Precision Medicine Clinic, both at George Washington University School of Medicine & Health Sciences, Washington, DC, in an email.
Testing is also limited by cultural barriers, lack of genetic literacy, and patients’ concerns that a positive result could lead to a loss of health insurance coverage, said Dr. Raj and Dr. Shankaranarayanan.
Paper Will Help Expand Use
A lack of consensus has also held back expansion. The new statement “may lead to increased and possibly judicious utilization of genetic testing in nephrology practices,” said Dr. Raj and Dr. Shankaranarayanan. “Most importantly, the panel has given specific guidance as to what type of genetic test platform is likely to yield the best and most cost-effective yield.”
The most effective use is “in monogenic kidney diseases and to a lesser extent in oligogenic kidney disease,” said Dr. Raj and Dr. Shankaranarayanan, adding that testing is of less-certain utility in polygenic kidney diseases, “where complex genetic and epigenetic factors determine the phenotype.”
Genetic testing might be especially useful “in atypical clinical presentations” and can help clinicians avoid unnecessary expensive and extensive investigations when multiple organ systems are involved, they said.
“Most importantly, [testing] might prevent unnecessary and potentially harmful treatment and enable targeted specific treatment, when available,” said Dr. Raj and Dr. Shankaranarayanan.
Dr. Franceschini and Dr. Shankaranarayanan reported no relevant financial relationships. Dr. Raj disclosed that he received consulting fees and honoraria from Novo Nordisk and is a national leader for the company’s Zeus trial, studying whether ziltivekimab reduces the risk for cardiovascular events in cardiovascular disease, CKD, and inflammation. He also participated in a study of Natera’s Renasight, a 385-gene panel for kidney disease.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF KIDNEY DISEASES
New ACOG Guidance Advises Clinicians on Cannabis Use for Gynecologic Pain
An increasing proportion of people are using cannabis products for pain, including that associated with gynecologic conditions, according to new guidance from the American College of Obstetricians and Gynecologists. The organization published its first guidance in July on the use of cannabis products for gynecologic pain.
“Many of our patients are using these products and many of our members are getting questions from their patients asking whether they should be using them,” Kimberly Gecsi, MD, a professor of ob.gyn. at Medical College of Wisconsin and Froedtert Health in Milwaukee, Wisconsin, and one of the document’s coauthors, said in an interview.* “We want ACOG members to walk away with some understanding that their patients are using these products, what the different products are, and the current state of the science so they can guide their patients about the potential advantages as well as the potential risks.”
Use of cannabis in the past month in the United States rose 38.2% between 2015 and 2019, according to the National Survey on Drug Use and Health. Other research using data from that survey found that US use of cannabis for medicinal purposes more than doubled, from 1.2% to 2.5% between 2013-2014 and 2019-2020, and use in states where it was legalized increased fourfold. Though little data exist on its use for gynecologic pain, at least one peer-reviewed online survey found that 61% of those who had never used it and 90% of those who had ever used it were willing to consider its use for gynecologic pain.
In assessing the current evidence, the researchers excluded studies looking at use of cannabis to manage symptoms related to cancer, obstetrics, or gynecologic malignancy. Of the remaining evidence, however, “there just isn’t enough data on gynecologic pain to really have tipped the scale toward a recommendation,” Dr. Gecsi said.
The consensus recommendations therefore state that current data are not sufficient to recommend or discourage use of cannabis products to treat pain linked to gynecologic conditions. Yet the potential for benefit suggests that “if they are already using these products, there’s no need to discourage them, especially if the patients feel they are getting some benefit from them,” Dr. Gecsi said.
The guidance also highlights the importance of clinicians being aware that their patients may be using these products and being prepared to discuss with them the limited data available as well as the theoretical benefits and potential negative effects for adult patients. In adolescent patients, however, the increased risk of negative cognitive effects and psychotic conditions currently appears to outweigh the theoretical benefits. Use of cannabis products in teens should therefore not be recommended until more data is available on the short-term and long-term effects of its use on adolescent brain development, the authors wrote.
Josephine Urbina, MD, MAS, an assistant professor of ob.gyn. and reproductive sciences at the University of California, San Francisco, said that the guidance confirms what most ob.gyns. suspected regarding the lack of data to support or refute the use of cannabis.
“Patients usually see cannabis as a last resort to control their pain,” Dr. Urbina added. “It seems that this decision to start using cannabis isn’t one that’s taken lightly, and they’re usually at their wits’ end. Some patients use cannabis as an adjunct so that they don’t have to rely on stronger pain medications like opioids, which we all know have a proven track record for being addicting.”
The ACOG guidance notes limited survey data suggesting that cannabis may help reduce patients’ use of opioids for pain relief, though there’s not enough data to confirm this potential benefit. The authors also highlight the limited data suggesting that PEA-transpolydatin may be effective for relieving pain related to primary dysmenorrhea, endometriosis, and chronic pelvic pain, but, again, there’s not yet enough data to formally recommend its use.
Current treatments for pain from gynecologic conditions depend on the cause of the pain, Dr. Gecsi said. One of the more common causes of pain, for example, is endometriosis, which can be treated with medications, including hormonal ones, or with surgery.
Other first-line treatments for pain, can include nonsteroidal anti-inflammatory drug and, for more complex cases, gonadotropin-releasing hormone agonists, antidepressants, and anticonvulsants. “Nonpharmacological treatments like physical therapy, acupuncture, cognitive-behavioral therapy and lifestyle changes, including diet and exercise, can also be beneficial,” Dr. Urbina added.
The new guidance also attempts to clarify the confusing legal landscape associated with cannabis use. In addition to the patchwork of state laws, federal distinctions in cannabis legality have been shifting in recent years. The 2018 Farm Bill defined any product with 0.3% or less tetrahydrocannabinol (THC) as hemp, which is now legal and commercially available in all states. That change introduced a wide range of topical and edible cannabidiol products to the market, even in states where marijuana is otherwise still illegal.
Products with a THC concentration greater than 0.3%, however, remain classified as a Schedule I drug, though the Justice Department proposed a rule in May to change that classification to Schedule III, which includes drugs such as ketamine, anabolic steroids, testosterone, and Tylenol with codeine. The guidance also includes a box of definitions for different types of cannabis products and differences in bioavailability, time to onset of effects, and duration of effects for different routes of exposure.
Kiran Kavipurapu, DO, JD, MPH, an assistant clinical professor and ob.gyn. residency program director at the University of California, Los Angeles, said the increasing availability and legalization of cannabis has meant that more patients are coming to their doctors’ offices having already tried it for medicinal purposes.
“Cannabis use discussions are often initiated by patients who are either inquiring about its benefits or because they have already tried it and want a physician to weigh in,” Dr. Kavipurapu said in an interview. “Over the past 5 years or so, this has become an increasingly common topic along with discussion of herbal or naturopathic remedies to supplement treatment of gynecologic conditions.”
Yet stigma about its use can lead patients to feel hesitant about bringing it up, Dr. Kavipurapu added. “I think it is necessary for clinicians to create a safe environment for patients to discuss their use of any and all therapies or supplements so their physician can assess for potential drug interactions or other harmful effects,” he said.
Dr. Gecsi agreed that this need to reassure patients was an important aspect of ACOG’s new guidance. Clinicians “should make sure that they strive to always foster a relationship with their patients where their patients can feel safe sharing their use and other things going on in their lives without feeling like they’re going to get in trouble,. Our job is not to put our patients at risk for any kind of legal or criminal problems.”
Meanwhile, the legal restrictions on cannabis remain a substantial barrier to the additional research that’s needed to make more informed recommendations about its use to patients, Dr. Gecsi said. But the inadequate amount of research goes beyond the challenges of studying cannabis in particular, Dr. Urbina noted.
“The paucity of research in women’s health, particularly in the realm of sexual and reproductive health care, underscores the urgent need to prioritize this topic in order to ensure comprehensive and equitable healthcare for women,” Dr. Urbina said. Underrepresentation of women’s health issues in clinical studies has led to knowledge gaps and “suboptimal treatment options for conditions unique to or more prevalent among women,” and it’s another reason for the lack of robust data on cannabis use for gynecologic-related pain.
“Prioritizing research in women’s health is essential to developing effective interventions, understanding gender-specific responses to treatments, and addressing the complex interplay of biological, social, and psychological factors affecting women’s well-being,” Dr. Urbina said. “Furthermore, advancing reproductive health research supports women’s reproductive autonomy, empowering them with the knowledge and resources to make informed decisions about their bodies and lives. By investing in robust, inclusive research, we can close existing gaps, improve health outcomes, and promote gender equity in healthcare — something that has been long overdue in this country.”
The guidance did not use external funding. Dr. Gecsi, Dr. Urbina, and Dr. Kavipurapu had no disclosures.
*This story was corrected on July 25, 2024.
An increasing proportion of people are using cannabis products for pain, including that associated with gynecologic conditions, according to new guidance from the American College of Obstetricians and Gynecologists. The organization published its first guidance in July on the use of cannabis products for gynecologic pain.
“Many of our patients are using these products and many of our members are getting questions from their patients asking whether they should be using them,” Kimberly Gecsi, MD, a professor of ob.gyn. at Medical College of Wisconsin and Froedtert Health in Milwaukee, Wisconsin, and one of the document’s coauthors, said in an interview.* “We want ACOG members to walk away with some understanding that their patients are using these products, what the different products are, and the current state of the science so they can guide their patients about the potential advantages as well as the potential risks.”
Use of cannabis in the past month in the United States rose 38.2% between 2015 and 2019, according to the National Survey on Drug Use and Health. Other research using data from that survey found that US use of cannabis for medicinal purposes more than doubled, from 1.2% to 2.5% between 2013-2014 and 2019-2020, and use in states where it was legalized increased fourfold. Though little data exist on its use for gynecologic pain, at least one peer-reviewed online survey found that 61% of those who had never used it and 90% of those who had ever used it were willing to consider its use for gynecologic pain.
In assessing the current evidence, the researchers excluded studies looking at use of cannabis to manage symptoms related to cancer, obstetrics, or gynecologic malignancy. Of the remaining evidence, however, “there just isn’t enough data on gynecologic pain to really have tipped the scale toward a recommendation,” Dr. Gecsi said.
The consensus recommendations therefore state that current data are not sufficient to recommend or discourage use of cannabis products to treat pain linked to gynecologic conditions. Yet the potential for benefit suggests that “if they are already using these products, there’s no need to discourage them, especially if the patients feel they are getting some benefit from them,” Dr. Gecsi said.
The guidance also highlights the importance of clinicians being aware that their patients may be using these products and being prepared to discuss with them the limited data available as well as the theoretical benefits and potential negative effects for adult patients. In adolescent patients, however, the increased risk of negative cognitive effects and psychotic conditions currently appears to outweigh the theoretical benefits. Use of cannabis products in teens should therefore not be recommended until more data is available on the short-term and long-term effects of its use on adolescent brain development, the authors wrote.
Josephine Urbina, MD, MAS, an assistant professor of ob.gyn. and reproductive sciences at the University of California, San Francisco, said that the guidance confirms what most ob.gyns. suspected regarding the lack of data to support or refute the use of cannabis.
“Patients usually see cannabis as a last resort to control their pain,” Dr. Urbina added. “It seems that this decision to start using cannabis isn’t one that’s taken lightly, and they’re usually at their wits’ end. Some patients use cannabis as an adjunct so that they don’t have to rely on stronger pain medications like opioids, which we all know have a proven track record for being addicting.”
The ACOG guidance notes limited survey data suggesting that cannabis may help reduce patients’ use of opioids for pain relief, though there’s not enough data to confirm this potential benefit. The authors also highlight the limited data suggesting that PEA-transpolydatin may be effective for relieving pain related to primary dysmenorrhea, endometriosis, and chronic pelvic pain, but, again, there’s not yet enough data to formally recommend its use.
Current treatments for pain from gynecologic conditions depend on the cause of the pain, Dr. Gecsi said. One of the more common causes of pain, for example, is endometriosis, which can be treated with medications, including hormonal ones, or with surgery.
Other first-line treatments for pain, can include nonsteroidal anti-inflammatory drug and, for more complex cases, gonadotropin-releasing hormone agonists, antidepressants, and anticonvulsants. “Nonpharmacological treatments like physical therapy, acupuncture, cognitive-behavioral therapy and lifestyle changes, including diet and exercise, can also be beneficial,” Dr. Urbina added.
The new guidance also attempts to clarify the confusing legal landscape associated with cannabis use. In addition to the patchwork of state laws, federal distinctions in cannabis legality have been shifting in recent years. The 2018 Farm Bill defined any product with 0.3% or less tetrahydrocannabinol (THC) as hemp, which is now legal and commercially available in all states. That change introduced a wide range of topical and edible cannabidiol products to the market, even in states where marijuana is otherwise still illegal.
Products with a THC concentration greater than 0.3%, however, remain classified as a Schedule I drug, though the Justice Department proposed a rule in May to change that classification to Schedule III, which includes drugs such as ketamine, anabolic steroids, testosterone, and Tylenol with codeine. The guidance also includes a box of definitions for different types of cannabis products and differences in bioavailability, time to onset of effects, and duration of effects for different routes of exposure.
Kiran Kavipurapu, DO, JD, MPH, an assistant clinical professor and ob.gyn. residency program director at the University of California, Los Angeles, said the increasing availability and legalization of cannabis has meant that more patients are coming to their doctors’ offices having already tried it for medicinal purposes.
“Cannabis use discussions are often initiated by patients who are either inquiring about its benefits or because they have already tried it and want a physician to weigh in,” Dr. Kavipurapu said in an interview. “Over the past 5 years or so, this has become an increasingly common topic along with discussion of herbal or naturopathic remedies to supplement treatment of gynecologic conditions.”
Yet stigma about its use can lead patients to feel hesitant about bringing it up, Dr. Kavipurapu added. “I think it is necessary for clinicians to create a safe environment for patients to discuss their use of any and all therapies or supplements so their physician can assess for potential drug interactions or other harmful effects,” he said.
Dr. Gecsi agreed that this need to reassure patients was an important aspect of ACOG’s new guidance. Clinicians “should make sure that they strive to always foster a relationship with their patients where their patients can feel safe sharing their use and other things going on in their lives without feeling like they’re going to get in trouble,. Our job is not to put our patients at risk for any kind of legal or criminal problems.”
Meanwhile, the legal restrictions on cannabis remain a substantial barrier to the additional research that’s needed to make more informed recommendations about its use to patients, Dr. Gecsi said. But the inadequate amount of research goes beyond the challenges of studying cannabis in particular, Dr. Urbina noted.
“The paucity of research in women’s health, particularly in the realm of sexual and reproductive health care, underscores the urgent need to prioritize this topic in order to ensure comprehensive and equitable healthcare for women,” Dr. Urbina said. Underrepresentation of women’s health issues in clinical studies has led to knowledge gaps and “suboptimal treatment options for conditions unique to or more prevalent among women,” and it’s another reason for the lack of robust data on cannabis use for gynecologic-related pain.
“Prioritizing research in women’s health is essential to developing effective interventions, understanding gender-specific responses to treatments, and addressing the complex interplay of biological, social, and psychological factors affecting women’s well-being,” Dr. Urbina said. “Furthermore, advancing reproductive health research supports women’s reproductive autonomy, empowering them with the knowledge and resources to make informed decisions about their bodies and lives. By investing in robust, inclusive research, we can close existing gaps, improve health outcomes, and promote gender equity in healthcare — something that has been long overdue in this country.”
The guidance did not use external funding. Dr. Gecsi, Dr. Urbina, and Dr. Kavipurapu had no disclosures.
*This story was corrected on July 25, 2024.
An increasing proportion of people are using cannabis products for pain, including that associated with gynecologic conditions, according to new guidance from the American College of Obstetricians and Gynecologists. The organization published its first guidance in July on the use of cannabis products for gynecologic pain.
“Many of our patients are using these products and many of our members are getting questions from their patients asking whether they should be using them,” Kimberly Gecsi, MD, a professor of ob.gyn. at Medical College of Wisconsin and Froedtert Health in Milwaukee, Wisconsin, and one of the document’s coauthors, said in an interview.* “We want ACOG members to walk away with some understanding that their patients are using these products, what the different products are, and the current state of the science so they can guide their patients about the potential advantages as well as the potential risks.”
Use of cannabis in the past month in the United States rose 38.2% between 2015 and 2019, according to the National Survey on Drug Use and Health. Other research using data from that survey found that US use of cannabis for medicinal purposes more than doubled, from 1.2% to 2.5% between 2013-2014 and 2019-2020, and use in states where it was legalized increased fourfold. Though little data exist on its use for gynecologic pain, at least one peer-reviewed online survey found that 61% of those who had never used it and 90% of those who had ever used it were willing to consider its use for gynecologic pain.
In assessing the current evidence, the researchers excluded studies looking at use of cannabis to manage symptoms related to cancer, obstetrics, or gynecologic malignancy. Of the remaining evidence, however, “there just isn’t enough data on gynecologic pain to really have tipped the scale toward a recommendation,” Dr. Gecsi said.
The consensus recommendations therefore state that current data are not sufficient to recommend or discourage use of cannabis products to treat pain linked to gynecologic conditions. Yet the potential for benefit suggests that “if they are already using these products, there’s no need to discourage them, especially if the patients feel they are getting some benefit from them,” Dr. Gecsi said.
The guidance also highlights the importance of clinicians being aware that their patients may be using these products and being prepared to discuss with them the limited data available as well as the theoretical benefits and potential negative effects for adult patients. In adolescent patients, however, the increased risk of negative cognitive effects and psychotic conditions currently appears to outweigh the theoretical benefits. Use of cannabis products in teens should therefore not be recommended until more data is available on the short-term and long-term effects of its use on adolescent brain development, the authors wrote.
Josephine Urbina, MD, MAS, an assistant professor of ob.gyn. and reproductive sciences at the University of California, San Francisco, said that the guidance confirms what most ob.gyns. suspected regarding the lack of data to support or refute the use of cannabis.
“Patients usually see cannabis as a last resort to control their pain,” Dr. Urbina added. “It seems that this decision to start using cannabis isn’t one that’s taken lightly, and they’re usually at their wits’ end. Some patients use cannabis as an adjunct so that they don’t have to rely on stronger pain medications like opioids, which we all know have a proven track record for being addicting.”
The ACOG guidance notes limited survey data suggesting that cannabis may help reduce patients’ use of opioids for pain relief, though there’s not enough data to confirm this potential benefit. The authors also highlight the limited data suggesting that PEA-transpolydatin may be effective for relieving pain related to primary dysmenorrhea, endometriosis, and chronic pelvic pain, but, again, there’s not yet enough data to formally recommend its use.
Current treatments for pain from gynecologic conditions depend on the cause of the pain, Dr. Gecsi said. One of the more common causes of pain, for example, is endometriosis, which can be treated with medications, including hormonal ones, or with surgery.
Other first-line treatments for pain, can include nonsteroidal anti-inflammatory drug and, for more complex cases, gonadotropin-releasing hormone agonists, antidepressants, and anticonvulsants. “Nonpharmacological treatments like physical therapy, acupuncture, cognitive-behavioral therapy and lifestyle changes, including diet and exercise, can also be beneficial,” Dr. Urbina added.
The new guidance also attempts to clarify the confusing legal landscape associated with cannabis use. In addition to the patchwork of state laws, federal distinctions in cannabis legality have been shifting in recent years. The 2018 Farm Bill defined any product with 0.3% or less tetrahydrocannabinol (THC) as hemp, which is now legal and commercially available in all states. That change introduced a wide range of topical and edible cannabidiol products to the market, even in states where marijuana is otherwise still illegal.
Products with a THC concentration greater than 0.3%, however, remain classified as a Schedule I drug, though the Justice Department proposed a rule in May to change that classification to Schedule III, which includes drugs such as ketamine, anabolic steroids, testosterone, and Tylenol with codeine. The guidance also includes a box of definitions for different types of cannabis products and differences in bioavailability, time to onset of effects, and duration of effects for different routes of exposure.
Kiran Kavipurapu, DO, JD, MPH, an assistant clinical professor and ob.gyn. residency program director at the University of California, Los Angeles, said the increasing availability and legalization of cannabis has meant that more patients are coming to their doctors’ offices having already tried it for medicinal purposes.
“Cannabis use discussions are often initiated by patients who are either inquiring about its benefits or because they have already tried it and want a physician to weigh in,” Dr. Kavipurapu said in an interview. “Over the past 5 years or so, this has become an increasingly common topic along with discussion of herbal or naturopathic remedies to supplement treatment of gynecologic conditions.”
Yet stigma about its use can lead patients to feel hesitant about bringing it up, Dr. Kavipurapu added. “I think it is necessary for clinicians to create a safe environment for patients to discuss their use of any and all therapies or supplements so their physician can assess for potential drug interactions or other harmful effects,” he said.
Dr. Gecsi agreed that this need to reassure patients was an important aspect of ACOG’s new guidance. Clinicians “should make sure that they strive to always foster a relationship with their patients where their patients can feel safe sharing their use and other things going on in their lives without feeling like they’re going to get in trouble,. Our job is not to put our patients at risk for any kind of legal or criminal problems.”
Meanwhile, the legal restrictions on cannabis remain a substantial barrier to the additional research that’s needed to make more informed recommendations about its use to patients, Dr. Gecsi said. But the inadequate amount of research goes beyond the challenges of studying cannabis in particular, Dr. Urbina noted.
“The paucity of research in women’s health, particularly in the realm of sexual and reproductive health care, underscores the urgent need to prioritize this topic in order to ensure comprehensive and equitable healthcare for women,” Dr. Urbina said. Underrepresentation of women’s health issues in clinical studies has led to knowledge gaps and “suboptimal treatment options for conditions unique to or more prevalent among women,” and it’s another reason for the lack of robust data on cannabis use for gynecologic-related pain.
“Prioritizing research in women’s health is essential to developing effective interventions, understanding gender-specific responses to treatments, and addressing the complex interplay of biological, social, and psychological factors affecting women’s well-being,” Dr. Urbina said. “Furthermore, advancing reproductive health research supports women’s reproductive autonomy, empowering them with the knowledge and resources to make informed decisions about their bodies and lives. By investing in robust, inclusive research, we can close existing gaps, improve health outcomes, and promote gender equity in healthcare — something that has been long overdue in this country.”
The guidance did not use external funding. Dr. Gecsi, Dr. Urbina, and Dr. Kavipurapu had no disclosures.
*This story was corrected on July 25, 2024.
‘Therapeutic Continuums’ Guide Systemic Sclerosis Treatment in Updated EULAR Recommendations
VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.
“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.
“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.
Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
‘Therapeutic Continuums’ Aid Disease Management
Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.
A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”
Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”
He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.
The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”
Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”
Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.
To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.
The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.
He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”
For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
Systemic Sclerosis Research Agenda and Recommendations Align
Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.
“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”
In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”
“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
Remission Elusive but Getting Closer
In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.
Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.
Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”
Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.
Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.
“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”
Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.
“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.
“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.
Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
‘Therapeutic Continuums’ Aid Disease Management
Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.
A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”
Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”
He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.
The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”
Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”
Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.
To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.
The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.
He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”
For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
Systemic Sclerosis Research Agenda and Recommendations Align
Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.
“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”
In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”
“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
Remission Elusive but Getting Closer
In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.
Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.
Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”
Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.
Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.
“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”
Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.
“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.
“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.
Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
‘Therapeutic Continuums’ Aid Disease Management
Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.
A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”
Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”
He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.
The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”
Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”
Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.
To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.
The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.
He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”
For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
Systemic Sclerosis Research Agenda and Recommendations Align
Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.
“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”
In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”
“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
Remission Elusive but Getting Closer
In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.
Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.
Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”
Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.
Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.
“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”
Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM EULAR 2024
Updated Guideline Reflects New Drugs for Type 2 Diabetes
Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.
The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.
Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
New Drugs
The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).
Recommendations
The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.
SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.
Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.
Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.
Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.
The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).
Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
Considerations for Practice
Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.
The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.
The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.
The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.
The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.
Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
New Drugs
The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).
Recommendations
The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.
SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.
Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.
Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.
Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.
The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).
Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
Considerations for Practice
Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.
The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.
The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.
The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.
The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.
Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
New Drugs
The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).
Recommendations
The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.
SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.
Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.
Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.
Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.
The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).
Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
Considerations for Practice
Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.
The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.
The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.
The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Acute Sore Throat in Primary Care: When to Reach for the Antibiotics
This transcript has been edited for clarity.
There is a helpful consensus from experts on the best management of patients with acute sore throat. This is a common problem in primary care, and one for which there is a lot of evidence, opinion, and ultimately overprescribing of antibiotics. This consensus presents a pragmatic clinical approach aimed at decreasing overprescribing, yet detecting which patients are likely to benefit from treatment with antibiotics.
Let’s first go over the evidence that forms the basis for the recommendations, then the recommended approach. First, a sore throat can be caused by many different viruses, as well as group A streptococcus (GAS), the group C streptococcus S dysgalactiae, and fusobacterium. We sometimes think of throat cultures as telling us the definitive etiology of a sore throat. In fact, children commonly are colonized with GAS even when not infected — 35% of the time, when GAS is detected on throat swab in a child, GAS is not the cause of the sore throat. Very few adults are colonized with GAS.
Sore throats are usually self-limited, whether they are treated with antibiotics or not, but occasionally complications can occur. Suppurative complications include peritonsillar abscess, sinusitis and sepsis. Nonsuppurative complications are primarily glomerulonephritis and rheumatic fever, which can lead to rheumatic heart disease.
Antibiotics. Antibiotics have three potential benefits in acute sore throat: to reduce the risk of developing rheumatic heart disease, reduce the duration and severity of symptoms, and treat suppurative complications. The risk for rheumatic heart disease has almost vanished in high-income countries, but not in low-income countries. Thus, antibiotic treatment of acute sore throat due to GAS may benefit those in living in, and those who recently emigrated from, low-income countries.
Patients with suppurative complications should be identified because antibiotics are important for this group. Although antibiotics are prescribed primarily to prevent rheumatic fever in this population, they may be mildly helpful in reducing a patient’s symptoms.
Testing. The sensitivity and specificity of high-quality point-of-care tests (POCTs) are on par with those of cultures, with the advantage that the results are available within minutes. Negative tests reduce unneeded antibiotic prescriptions.
Given this evidence, the authors recommend an approach that puts a lot of emphasis on two major things: the risk for rheumatic fever, and clinical assessment. On the basis of these factors, a decision is made about the utility of POCTs and treatment with antibiotics for GAS. The risk for rheumatic fever is based on epidemiology: If the patient is in a low-income country or has recently immigrated from one, then the risk is high, and if not, the risk is low.
Complicated vs uncomplicated? This is determined by clinical assessment of the severity of the patient’s illness, including general appearance. Uncomplicated sore throat means that the patient:
- Is not getting worse after 3 days of illness
- Has a duration of illness ≤ 5 days or is getting better after day 5
- Has mild to moderate symptom severity (bilateral throat pain, the ability to open the mouth fully, and absence of a sandpaper or scarlatiniform rash or strawberry tongue)
For patients with uncomplicated sore throat and low risk for rheumatic fever, the main goals are to reduce antibiotic use and provide symptomatic relief. For these patients, an assessment such as the Centor score can be done. Those with a low Centor score (0-2) can be treated with analgesics and there is no need for a POCT.
In patients with a higher Centor score, the consensus gives two choices: They can either be tested (and treated if the testing is positive), or it is reasonable to forgo testing and use a wait-and-see strategy, with reevaluation if they are getting worse after day 3 or not improving after day 5 days of their illness. Illnesses that last longer than 5 days with sore throat and fatigue should prompt consideration of alternative diagnoses, such as infectious mononucleosis.
For patients with potentially complicated sore throat — including indicators such as worsening symptoms after 3 days or worsening after initiation of antibiotics, inability to open the mouth fully, unilateral neck pain or swelling, or rigors — should undergo a careful evaluation. The need for further testing in these patients, including labs and imaging, should be decided on a case-by-case basis. If the patient appears seriously ill, don’t rely solely on POCT for GAS, but think about other diagnoses.
Rheumatic fever. The approach is very different in patients at high risk for rheumatic fever. POCT for GAS is recommended irrespective of their clinical score, and antibiotics should be prescribed if it’s positive for GAS. If a POCT is unavailable, then the consensus recommends prescribing antibiotics for all high-risk patients who have acute sore throat.
This approach is sensible and puts a lot of emphasis on clinical evaluation, though it should be noted that this approach is considerably different from that in the 2012 Infectious Diseases Society of America guidelines.
Dr. Skolnik, professor, Department of Family Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
There is a helpful consensus from experts on the best management of patients with acute sore throat. This is a common problem in primary care, and one for which there is a lot of evidence, opinion, and ultimately overprescribing of antibiotics. This consensus presents a pragmatic clinical approach aimed at decreasing overprescribing, yet detecting which patients are likely to benefit from treatment with antibiotics.
Let’s first go over the evidence that forms the basis for the recommendations, then the recommended approach. First, a sore throat can be caused by many different viruses, as well as group A streptococcus (GAS), the group C streptococcus S dysgalactiae, and fusobacterium. We sometimes think of throat cultures as telling us the definitive etiology of a sore throat. In fact, children commonly are colonized with GAS even when not infected — 35% of the time, when GAS is detected on throat swab in a child, GAS is not the cause of the sore throat. Very few adults are colonized with GAS.
Sore throats are usually self-limited, whether they are treated with antibiotics or not, but occasionally complications can occur. Suppurative complications include peritonsillar abscess, sinusitis and sepsis. Nonsuppurative complications are primarily glomerulonephritis and rheumatic fever, which can lead to rheumatic heart disease.
Antibiotics. Antibiotics have three potential benefits in acute sore throat: to reduce the risk of developing rheumatic heart disease, reduce the duration and severity of symptoms, and treat suppurative complications. The risk for rheumatic heart disease has almost vanished in high-income countries, but not in low-income countries. Thus, antibiotic treatment of acute sore throat due to GAS may benefit those in living in, and those who recently emigrated from, low-income countries.
Patients with suppurative complications should be identified because antibiotics are important for this group. Although antibiotics are prescribed primarily to prevent rheumatic fever in this population, they may be mildly helpful in reducing a patient’s symptoms.
Testing. The sensitivity and specificity of high-quality point-of-care tests (POCTs) are on par with those of cultures, with the advantage that the results are available within minutes. Negative tests reduce unneeded antibiotic prescriptions.
Given this evidence, the authors recommend an approach that puts a lot of emphasis on two major things: the risk for rheumatic fever, and clinical assessment. On the basis of these factors, a decision is made about the utility of POCTs and treatment with antibiotics for GAS. The risk for rheumatic fever is based on epidemiology: If the patient is in a low-income country or has recently immigrated from one, then the risk is high, and if not, the risk is low.
Complicated vs uncomplicated? This is determined by clinical assessment of the severity of the patient’s illness, including general appearance. Uncomplicated sore throat means that the patient:
- Is not getting worse after 3 days of illness
- Has a duration of illness ≤ 5 days or is getting better after day 5
- Has mild to moderate symptom severity (bilateral throat pain, the ability to open the mouth fully, and absence of a sandpaper or scarlatiniform rash or strawberry tongue)
For patients with uncomplicated sore throat and low risk for rheumatic fever, the main goals are to reduce antibiotic use and provide symptomatic relief. For these patients, an assessment such as the Centor score can be done. Those with a low Centor score (0-2) can be treated with analgesics and there is no need for a POCT.
In patients with a higher Centor score, the consensus gives two choices: They can either be tested (and treated if the testing is positive), or it is reasonable to forgo testing and use a wait-and-see strategy, with reevaluation if they are getting worse after day 3 or not improving after day 5 days of their illness. Illnesses that last longer than 5 days with sore throat and fatigue should prompt consideration of alternative diagnoses, such as infectious mononucleosis.
For patients with potentially complicated sore throat — including indicators such as worsening symptoms after 3 days or worsening after initiation of antibiotics, inability to open the mouth fully, unilateral neck pain or swelling, or rigors — should undergo a careful evaluation. The need for further testing in these patients, including labs and imaging, should be decided on a case-by-case basis. If the patient appears seriously ill, don’t rely solely on POCT for GAS, but think about other diagnoses.
Rheumatic fever. The approach is very different in patients at high risk for rheumatic fever. POCT for GAS is recommended irrespective of their clinical score, and antibiotics should be prescribed if it’s positive for GAS. If a POCT is unavailable, then the consensus recommends prescribing antibiotics for all high-risk patients who have acute sore throat.
This approach is sensible and puts a lot of emphasis on clinical evaluation, though it should be noted that this approach is considerably different from that in the 2012 Infectious Diseases Society of America guidelines.
Dr. Skolnik, professor, Department of Family Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
There is a helpful consensus from experts on the best management of patients with acute sore throat. This is a common problem in primary care, and one for which there is a lot of evidence, opinion, and ultimately overprescribing of antibiotics. This consensus presents a pragmatic clinical approach aimed at decreasing overprescribing, yet detecting which patients are likely to benefit from treatment with antibiotics.
Let’s first go over the evidence that forms the basis for the recommendations, then the recommended approach. First, a sore throat can be caused by many different viruses, as well as group A streptococcus (GAS), the group C streptococcus S dysgalactiae, and fusobacterium. We sometimes think of throat cultures as telling us the definitive etiology of a sore throat. In fact, children commonly are colonized with GAS even when not infected — 35% of the time, when GAS is detected on throat swab in a child, GAS is not the cause of the sore throat. Very few adults are colonized with GAS.
Sore throats are usually self-limited, whether they are treated with antibiotics or not, but occasionally complications can occur. Suppurative complications include peritonsillar abscess, sinusitis and sepsis. Nonsuppurative complications are primarily glomerulonephritis and rheumatic fever, which can lead to rheumatic heart disease.
Antibiotics. Antibiotics have three potential benefits in acute sore throat: to reduce the risk of developing rheumatic heart disease, reduce the duration and severity of symptoms, and treat suppurative complications. The risk for rheumatic heart disease has almost vanished in high-income countries, but not in low-income countries. Thus, antibiotic treatment of acute sore throat due to GAS may benefit those in living in, and those who recently emigrated from, low-income countries.
Patients with suppurative complications should be identified because antibiotics are important for this group. Although antibiotics are prescribed primarily to prevent rheumatic fever in this population, they may be mildly helpful in reducing a patient’s symptoms.
Testing. The sensitivity and specificity of high-quality point-of-care tests (POCTs) are on par with those of cultures, with the advantage that the results are available within minutes. Negative tests reduce unneeded antibiotic prescriptions.
Given this evidence, the authors recommend an approach that puts a lot of emphasis on two major things: the risk for rheumatic fever, and clinical assessment. On the basis of these factors, a decision is made about the utility of POCTs and treatment with antibiotics for GAS. The risk for rheumatic fever is based on epidemiology: If the patient is in a low-income country or has recently immigrated from one, then the risk is high, and if not, the risk is low.
Complicated vs uncomplicated? This is determined by clinical assessment of the severity of the patient’s illness, including general appearance. Uncomplicated sore throat means that the patient:
- Is not getting worse after 3 days of illness
- Has a duration of illness ≤ 5 days or is getting better after day 5
- Has mild to moderate symptom severity (bilateral throat pain, the ability to open the mouth fully, and absence of a sandpaper or scarlatiniform rash or strawberry tongue)
For patients with uncomplicated sore throat and low risk for rheumatic fever, the main goals are to reduce antibiotic use and provide symptomatic relief. For these patients, an assessment such as the Centor score can be done. Those with a low Centor score (0-2) can be treated with analgesics and there is no need for a POCT.
In patients with a higher Centor score, the consensus gives two choices: They can either be tested (and treated if the testing is positive), or it is reasonable to forgo testing and use a wait-and-see strategy, with reevaluation if they are getting worse after day 3 or not improving after day 5 days of their illness. Illnesses that last longer than 5 days with sore throat and fatigue should prompt consideration of alternative diagnoses, such as infectious mononucleosis.
For patients with potentially complicated sore throat — including indicators such as worsening symptoms after 3 days or worsening after initiation of antibiotics, inability to open the mouth fully, unilateral neck pain or swelling, or rigors — should undergo a careful evaluation. The need for further testing in these patients, including labs and imaging, should be decided on a case-by-case basis. If the patient appears seriously ill, don’t rely solely on POCT for GAS, but think about other diagnoses.
Rheumatic fever. The approach is very different in patients at high risk for rheumatic fever. POCT for GAS is recommended irrespective of their clinical score, and antibiotics should be prescribed if it’s positive for GAS. If a POCT is unavailable, then the consensus recommends prescribing antibiotics for all high-risk patients who have acute sore throat.
This approach is sensible and puts a lot of emphasis on clinical evaluation, though it should be noted that this approach is considerably different from that in the 2012 Infectious Diseases Society of America guidelines.
Dr. Skolnik, professor, Department of Family Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article appeared on Medscape.com.
USPSTF Draft Recommendations Support More Options for Osteoporosis Screening, Seek More Research in Men
An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.
The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.
The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.
The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.
The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.
“It provides them with more options instead of telling them, ‘You have to do it this way,’ ” Dr. Davis said.
The task force’s draft recommendation is not meant to apply to people with secondary osteoporosis due to an underlying medical condition such as cancer, metabolic bone diseases or hyperthyroidism, or chronic use of a medication associated with bone loss.
Rajesh K. Jain, MD, who was not involved with the USPSTF work, read the draft recommendations at the request of this news organization. In an email, he said he generally agreed with the decision to largely stick to the 2018 recommendations for women.
He also noted that there’s still a lack of a clear direction for physicians about assessing osteoporosis risk in men. But multiple randomized control trials of osteoporosis drugs seem to suggest these medicines work for both sexes, said Dr. Jain, who is the endocrinology fellowship program director at University of Chicago Medicine, Chicago.
The USPSTF draft also would reiterate the current “I” grade about screening men for osteoporosis.
An “I” grade means the task force found the current body of available evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men.
“Since there is no recommendation right now, it would have seemed sensible to include a recommendation to screen men with prior fracture or other risk factors for osteoporosis, much like they do for younger women,” Dr. Jain said.
Insufficient Evidence
The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.
A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)
The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.
“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.
“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.
There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.
The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
Risk Factors, Concerns About Tests
The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:
- Increasing age
- Low body mass index
- Excessive alcohol intake
- Current smoking
- Chronic corticosteroid use
- History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
- Hypogonadism
The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.
“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.
Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.
Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
A version of this article appeared on Medscape.com.
An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.
The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.
The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.
The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.
The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.
“It provides them with more options instead of telling them, ‘You have to do it this way,’ ” Dr. Davis said.
The task force’s draft recommendation is not meant to apply to people with secondary osteoporosis due to an underlying medical condition such as cancer, metabolic bone diseases or hyperthyroidism, or chronic use of a medication associated with bone loss.
Rajesh K. Jain, MD, who was not involved with the USPSTF work, read the draft recommendations at the request of this news organization. In an email, he said he generally agreed with the decision to largely stick to the 2018 recommendations for women.
He also noted that there’s still a lack of a clear direction for physicians about assessing osteoporosis risk in men. But multiple randomized control trials of osteoporosis drugs seem to suggest these medicines work for both sexes, said Dr. Jain, who is the endocrinology fellowship program director at University of Chicago Medicine, Chicago.
The USPSTF draft also would reiterate the current “I” grade about screening men for osteoporosis.
An “I” grade means the task force found the current body of available evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men.
“Since there is no recommendation right now, it would have seemed sensible to include a recommendation to screen men with prior fracture or other risk factors for osteoporosis, much like they do for younger women,” Dr. Jain said.
Insufficient Evidence
The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.
A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)
The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.
“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.
“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.
There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.
The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
Risk Factors, Concerns About Tests
The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:
- Increasing age
- Low body mass index
- Excessive alcohol intake
- Current smoking
- Chronic corticosteroid use
- History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
- Hypogonadism
The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.
“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.
Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.
Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
A version of this article appeared on Medscape.com.
An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.
The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.
The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.
The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.
The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.
“It provides them with more options instead of telling them, ‘You have to do it this way,’ ” Dr. Davis said.
The task force’s draft recommendation is not meant to apply to people with secondary osteoporosis due to an underlying medical condition such as cancer, metabolic bone diseases or hyperthyroidism, or chronic use of a medication associated with bone loss.
Rajesh K. Jain, MD, who was not involved with the USPSTF work, read the draft recommendations at the request of this news organization. In an email, he said he generally agreed with the decision to largely stick to the 2018 recommendations for women.
He also noted that there’s still a lack of a clear direction for physicians about assessing osteoporosis risk in men. But multiple randomized control trials of osteoporosis drugs seem to suggest these medicines work for both sexes, said Dr. Jain, who is the endocrinology fellowship program director at University of Chicago Medicine, Chicago.
The USPSTF draft also would reiterate the current “I” grade about screening men for osteoporosis.
An “I” grade means the task force found the current body of available evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men.
“Since there is no recommendation right now, it would have seemed sensible to include a recommendation to screen men with prior fracture or other risk factors for osteoporosis, much like they do for younger women,” Dr. Jain said.
Insufficient Evidence
The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.
A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)
The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.
“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.
“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.
There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.
The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
Risk Factors, Concerns About Tests
The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:
- Increasing age
- Low body mass index
- Excessive alcohol intake
- Current smoking
- Chronic corticosteroid use
- History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
- Hypogonadism
The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.
“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.
Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.
Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
A version of this article appeared on Medscape.com.