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Exciting opportunities for tobacco treatment
FROM THE CHEST TOBACCO/VAPING WORK GROUP –
The recent changes enacted by the Centers for Medicare & Medicaid Services (CMS) are creating unprecedented opportunities for pulmonologists and medical centers to help treat people with tobacco use disorder. As we face a critical moment in the fight against tobacco-related morbidity and mortality, it is essential that we leverage these changes. In doing so, CHEST aims to serve as an active bridge, informing health care providers of this unique federal opportunity that benefits both patients and clinicians.
A quick primer on “incident to” services
These CMS changes create an important shift in how “incident to” services can be billed. These are any services that are incident to (occur because of) a provider evaluation. These previously required direct supervision of the provider (in the same building) to be billed at the provider rate. Now “general supervision” suffices, which means the physician can be available by phone/video call. These services can then often be billed at a higher rate. In the case of treating dependence on tobacco products, any tobacco treatment specialist (TTS) employed by a practice who cares for the patient subsequent to the initial encounter can now be reimbursed in an increased manner. Better reimbursement for this vital service will ideally lead to better utilization of these resources and better public health.
The Medicare solution is here
With the CMS rule changes in 2023 and their reaffirmation in 2024, the structure has been put in place to allow physicians, medical centers, and TTSs to create contractual relationships that can significantly improve patient care. TTSs are health care professionals from a wide variety of disciplines who have received specialized training in tobacco and nicotine addiction and treatment strategies. By expanding billing and, thus, service opportunities, these CMS modifications empower health care providers to leverage the existing fee-for-service model, translating to better care and sustainable revenue streams.
Key changes in the CMS 2023 rule
One of the most notable changes involves the supervision requirements for auxiliary personnel, which now permit general supervision. Specifically, physicians are not required to be physically present during clinical encounters but can supervise TTSs virtually through real-time audio/video technology. This is a vital shift that enhances flexibility in patient care and expands the capabilities of health care teams.
According to 42 CFR § 410.26, TTSs qualify as auxiliary health care providers, meaning that they can operate under the supervision of a physician or other designated providers. This revised framework gives practices maximum autonomy in their staffing models and enhances their ability to offer comprehensive care. For example, TTSs can function as patient navigators, ensuring patients using tobacco receive medically appropriate early lung cancer screening and other related medical services.
Expanding access to behavioral health services
The changes aim not only to increase the efficiency of health care delivery but also to reflect a commitment to expanding access to vital behavioral health services. Key takeaways from a summary of the CMS 2023 rule include:
- The goal of these changes is to enhance access to behavioral health services across the board.
- The change in supervision requirements applies to auxiliary personnel offering behavioral health services incident to a physician’s services.
- Both patients and physicians will benefit from an expanded clinical team and improved reimbursement options for the services provided.
By leveraging these opportunities, physicians and their teams can collaborate with TTSs to make significant strides in helping patients address and overcome their dependence on tobacco and nicotine.
The outlook: CMS 2024 rule
The current outlook for 2024 and beyond promises even more opportunities as part of CMS’ ongoing Behavioral Health Strategy. This includes enabling mental health counselors (MHCs) and marriage and family therapists (MFTs) to bill Medicare independently, initiating vital coverage for mental health services that align with tobacco cessation efforts.
Physicians and medical centers can contract with MFTs and MHCs who are TTSs to provide tobacco addiction services. TTSs will serve as essential partners in multidisciplinary care teams, enhancing the overall health care landscape while ensuring that patients receive comprehensive support tailored to their needs.
Telehealth policy changes: Making services accessible
The White House also recently reinforced the importance of telehealth services, providing further avenues for TTSs to reach patients effectively. With expanded geographic locations for service delivery, care can be provided from virtually anywhere, including when the patient is at home.
Key telehealth provisions include:
- Extended telehealth services through 2024
- Elimination of in-person requirements for mental health services
- Expanded eligibility for providers qualified to provide telehealth services
Practical implications for providers
These developments not only simplify the establishment of tobacco treatment programs but also create better avenues to develop partnerships between physicians, hospitals, medical centers, multidisciplinary practices, and TTSs. Importantly, these clinicians will be compensated directly for the tobacco treatment services they provide.
Conclusion
This is a pivotal moment for pulmonologists and TTSs to meaningfully claim their place within the health care space. As we strive to “make smoking history,” we must act on these CMS opportunities. As providers, we must be proactive, collaborate across disciplines, and serve as advocates for our patients.
Together, we can turn the tide against tobacco use and improve health outcomes nationwide.
Call to action
CHEST encourages all health care professionals to engage with the available resources, collaborate with TTSs, and take appropriate advantage of these new policies for the benefit of our patients. Let’s work together to ensure that we seize this moment and make a real difference in the lives of those affected by tobacco addiction.
Those interested in more information—or to access additional resources and assistance in locating TTSs—please contact Matthew Bars at [email protected] or +1 (800) 45-SMOKE.
FROM THE CHEST TOBACCO/VAPING WORK GROUP –
The recent changes enacted by the Centers for Medicare & Medicaid Services (CMS) are creating unprecedented opportunities for pulmonologists and medical centers to help treat people with tobacco use disorder. As we face a critical moment in the fight against tobacco-related morbidity and mortality, it is essential that we leverage these changes. In doing so, CHEST aims to serve as an active bridge, informing health care providers of this unique federal opportunity that benefits both patients and clinicians.
A quick primer on “incident to” services
These CMS changes create an important shift in how “incident to” services can be billed. These are any services that are incident to (occur because of) a provider evaluation. These previously required direct supervision of the provider (in the same building) to be billed at the provider rate. Now “general supervision” suffices, which means the physician can be available by phone/video call. These services can then often be billed at a higher rate. In the case of treating dependence on tobacco products, any tobacco treatment specialist (TTS) employed by a practice who cares for the patient subsequent to the initial encounter can now be reimbursed in an increased manner. Better reimbursement for this vital service will ideally lead to better utilization of these resources and better public health.
The Medicare solution is here
With the CMS rule changes in 2023 and their reaffirmation in 2024, the structure has been put in place to allow physicians, medical centers, and TTSs to create contractual relationships that can significantly improve patient care. TTSs are health care professionals from a wide variety of disciplines who have received specialized training in tobacco and nicotine addiction and treatment strategies. By expanding billing and, thus, service opportunities, these CMS modifications empower health care providers to leverage the existing fee-for-service model, translating to better care and sustainable revenue streams.
Key changes in the CMS 2023 rule
One of the most notable changes involves the supervision requirements for auxiliary personnel, which now permit general supervision. Specifically, physicians are not required to be physically present during clinical encounters but can supervise TTSs virtually through real-time audio/video technology. This is a vital shift that enhances flexibility in patient care and expands the capabilities of health care teams.
According to 42 CFR § 410.26, TTSs qualify as auxiliary health care providers, meaning that they can operate under the supervision of a physician or other designated providers. This revised framework gives practices maximum autonomy in their staffing models and enhances their ability to offer comprehensive care. For example, TTSs can function as patient navigators, ensuring patients using tobacco receive medically appropriate early lung cancer screening and other related medical services.
Expanding access to behavioral health services
The changes aim not only to increase the efficiency of health care delivery but also to reflect a commitment to expanding access to vital behavioral health services. Key takeaways from a summary of the CMS 2023 rule include:
- The goal of these changes is to enhance access to behavioral health services across the board.
- The change in supervision requirements applies to auxiliary personnel offering behavioral health services incident to a physician’s services.
- Both patients and physicians will benefit from an expanded clinical team and improved reimbursement options for the services provided.
By leveraging these opportunities, physicians and their teams can collaborate with TTSs to make significant strides in helping patients address and overcome their dependence on tobacco and nicotine.
The outlook: CMS 2024 rule
The current outlook for 2024 and beyond promises even more opportunities as part of CMS’ ongoing Behavioral Health Strategy. This includes enabling mental health counselors (MHCs) and marriage and family therapists (MFTs) to bill Medicare independently, initiating vital coverage for mental health services that align with tobacco cessation efforts.
Physicians and medical centers can contract with MFTs and MHCs who are TTSs to provide tobacco addiction services. TTSs will serve as essential partners in multidisciplinary care teams, enhancing the overall health care landscape while ensuring that patients receive comprehensive support tailored to their needs.
Telehealth policy changes: Making services accessible
The White House also recently reinforced the importance of telehealth services, providing further avenues for TTSs to reach patients effectively. With expanded geographic locations for service delivery, care can be provided from virtually anywhere, including when the patient is at home.
Key telehealth provisions include:
- Extended telehealth services through 2024
- Elimination of in-person requirements for mental health services
- Expanded eligibility for providers qualified to provide telehealth services
Practical implications for providers
These developments not only simplify the establishment of tobacco treatment programs but also create better avenues to develop partnerships between physicians, hospitals, medical centers, multidisciplinary practices, and TTSs. Importantly, these clinicians will be compensated directly for the tobacco treatment services they provide.
Conclusion
This is a pivotal moment for pulmonologists and TTSs to meaningfully claim their place within the health care space. As we strive to “make smoking history,” we must act on these CMS opportunities. As providers, we must be proactive, collaborate across disciplines, and serve as advocates for our patients.
Together, we can turn the tide against tobacco use and improve health outcomes nationwide.
Call to action
CHEST encourages all health care professionals to engage with the available resources, collaborate with TTSs, and take appropriate advantage of these new policies for the benefit of our patients. Let’s work together to ensure that we seize this moment and make a real difference in the lives of those affected by tobacco addiction.
Those interested in more information—or to access additional resources and assistance in locating TTSs—please contact Matthew Bars at [email protected] or +1 (800) 45-SMOKE.
FROM THE CHEST TOBACCO/VAPING WORK GROUP –
The recent changes enacted by the Centers for Medicare & Medicaid Services (CMS) are creating unprecedented opportunities for pulmonologists and medical centers to help treat people with tobacco use disorder. As we face a critical moment in the fight against tobacco-related morbidity and mortality, it is essential that we leverage these changes. In doing so, CHEST aims to serve as an active bridge, informing health care providers of this unique federal opportunity that benefits both patients and clinicians.
A quick primer on “incident to” services
These CMS changes create an important shift in how “incident to” services can be billed. These are any services that are incident to (occur because of) a provider evaluation. These previously required direct supervision of the provider (in the same building) to be billed at the provider rate. Now “general supervision” suffices, which means the physician can be available by phone/video call. These services can then often be billed at a higher rate. In the case of treating dependence on tobacco products, any tobacco treatment specialist (TTS) employed by a practice who cares for the patient subsequent to the initial encounter can now be reimbursed in an increased manner. Better reimbursement for this vital service will ideally lead to better utilization of these resources and better public health.
The Medicare solution is here
With the CMS rule changes in 2023 and their reaffirmation in 2024, the structure has been put in place to allow physicians, medical centers, and TTSs to create contractual relationships that can significantly improve patient care. TTSs are health care professionals from a wide variety of disciplines who have received specialized training in tobacco and nicotine addiction and treatment strategies. By expanding billing and, thus, service opportunities, these CMS modifications empower health care providers to leverage the existing fee-for-service model, translating to better care and sustainable revenue streams.
Key changes in the CMS 2023 rule
One of the most notable changes involves the supervision requirements for auxiliary personnel, which now permit general supervision. Specifically, physicians are not required to be physically present during clinical encounters but can supervise TTSs virtually through real-time audio/video technology. This is a vital shift that enhances flexibility in patient care and expands the capabilities of health care teams.
According to 42 CFR § 410.26, TTSs qualify as auxiliary health care providers, meaning that they can operate under the supervision of a physician or other designated providers. This revised framework gives practices maximum autonomy in their staffing models and enhances their ability to offer comprehensive care. For example, TTSs can function as patient navigators, ensuring patients using tobacco receive medically appropriate early lung cancer screening and other related medical services.
Expanding access to behavioral health services
The changes aim not only to increase the efficiency of health care delivery but also to reflect a commitment to expanding access to vital behavioral health services. Key takeaways from a summary of the CMS 2023 rule include:
- The goal of these changes is to enhance access to behavioral health services across the board.
- The change in supervision requirements applies to auxiliary personnel offering behavioral health services incident to a physician’s services.
- Both patients and physicians will benefit from an expanded clinical team and improved reimbursement options for the services provided.
By leveraging these opportunities, physicians and their teams can collaborate with TTSs to make significant strides in helping patients address and overcome their dependence on tobacco and nicotine.
The outlook: CMS 2024 rule
The current outlook for 2024 and beyond promises even more opportunities as part of CMS’ ongoing Behavioral Health Strategy. This includes enabling mental health counselors (MHCs) and marriage and family therapists (MFTs) to bill Medicare independently, initiating vital coverage for mental health services that align with tobacco cessation efforts.
Physicians and medical centers can contract with MFTs and MHCs who are TTSs to provide tobacco addiction services. TTSs will serve as essential partners in multidisciplinary care teams, enhancing the overall health care landscape while ensuring that patients receive comprehensive support tailored to their needs.
Telehealth policy changes: Making services accessible
The White House also recently reinforced the importance of telehealth services, providing further avenues for TTSs to reach patients effectively. With expanded geographic locations for service delivery, care can be provided from virtually anywhere, including when the patient is at home.
Key telehealth provisions include:
- Extended telehealth services through 2024
- Elimination of in-person requirements for mental health services
- Expanded eligibility for providers qualified to provide telehealth services
Practical implications for providers
These developments not only simplify the establishment of tobacco treatment programs but also create better avenues to develop partnerships between physicians, hospitals, medical centers, multidisciplinary practices, and TTSs. Importantly, these clinicians will be compensated directly for the tobacco treatment services they provide.
Conclusion
This is a pivotal moment for pulmonologists and TTSs to meaningfully claim their place within the health care space. As we strive to “make smoking history,” we must act on these CMS opportunities. As providers, we must be proactive, collaborate across disciplines, and serve as advocates for our patients.
Together, we can turn the tide against tobacco use and improve health outcomes nationwide.
Call to action
CHEST encourages all health care professionals to engage with the available resources, collaborate with TTSs, and take appropriate advantage of these new policies for the benefit of our patients. Let’s work together to ensure that we seize this moment and make a real difference in the lives of those affected by tobacco addiction.
Those interested in more information—or to access additional resources and assistance in locating TTSs—please contact Matthew Bars at [email protected] or +1 (800) 45-SMOKE.
Top reads from the CHEST journal portfolio
Journal CHEST®
By Claire Launois, MD, PhD, and colleagues
It has long been a critique of studies that evaluate the impact of positive airway pressure (PAP) adherence on positive health outcomes that patients who are more adherent to PAP may also be more adherent to other health behaviors that contribute to those positive outcomes, such as incident cardiac events in patients with OSA. An association was found between multiple proxies of the healthy adherer effect and later PAP adherence in patients with OSA, the highest being related to proxies of cardiovascular health. A preceding reduction in health care costs was also found in these patients. These findings may help contribute to interpretation and validation of new studies to help us better understand the impact of PAP treatment of OSA.
– Commentary by Sreelatha Naik, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
By Burton H. Shen, MD, and colleagues
Asthma is a common reason for hospital admission. Between 5% and 35% of patients who are admitted due to asthma are also admitted to the ICU during their hospital stay. For adolescents and young adults, there is variability in admission to the PICU vs adult ICU. This study specifically evaluated patients aged 12 to 26 years old and included hospitals with both a PICU and an adult ICU. The results show us that age, rather than specific clinical characteristics, is the strongest predictor for PICU admission. Patients aged 18 years and younger were more likely to be admitted to the PICU. This is an important consideration, as hospital bedspace is often more limited during viral season in pediatric hospitals and PICUs. This information is also important for outpatient asthma providers to consider as they counsel their patients and provide long-term management before and after these hospital stays.
– Commentary by Lisa Ulrich, MD, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Short-Acting Beta-Agonists, Antibiotics, Oral Corticosteroids, and the Associated Burden of COPD
By Mohit Bhutani, MD, FCCP, and colleagues
This study notably highlights the fact that high frequency use of short-acting beta-agonists, antibiotics, and oral corticosteroids may not directly raise the likelihood of an exacerbation but rather may be a sign of worsening disease or poorly managed COPD.
Future studies should investigate the factors that contribute to patients’ frequent prescription use, such as understanding the underlying causes of their exacerbations and other pertinent factors. Additionally, details about patient adherence, a complete clinical history, and the treatment of any further chronic disorders are pivotal for a more complete picture. Enhanced methods for recognizing mild/moderate and severe exacerbations, including patient-reported outcomes, in order to have a better understanding of the influence on drug use and outcomes will be extremely helpful as well. To understand how medications impact results, further studies should look for causal links between medication use and exacerbations.
Lastly, Canadian research on COPD definitely offers insightful information, but when extrapolating these results to the United States, one must take into account variations in the health care system, demographics, and regional patterns along with social determinants of health.
– Commentary by Humayun Anjum, MD, FCCP, Member of the CHEST Physician Editorial Board
Journal CHEST®
By Claire Launois, MD, PhD, and colleagues
It has long been a critique of studies that evaluate the impact of positive airway pressure (PAP) adherence on positive health outcomes that patients who are more adherent to PAP may also be more adherent to other health behaviors that contribute to those positive outcomes, such as incident cardiac events in patients with OSA. An association was found between multiple proxies of the healthy adherer effect and later PAP adherence in patients with OSA, the highest being related to proxies of cardiovascular health. A preceding reduction in health care costs was also found in these patients. These findings may help contribute to interpretation and validation of new studies to help us better understand the impact of PAP treatment of OSA.
– Commentary by Sreelatha Naik, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
By Burton H. Shen, MD, and colleagues
Asthma is a common reason for hospital admission. Between 5% and 35% of patients who are admitted due to asthma are also admitted to the ICU during their hospital stay. For adolescents and young adults, there is variability in admission to the PICU vs adult ICU. This study specifically evaluated patients aged 12 to 26 years old and included hospitals with both a PICU and an adult ICU. The results show us that age, rather than specific clinical characteristics, is the strongest predictor for PICU admission. Patients aged 18 years and younger were more likely to be admitted to the PICU. This is an important consideration, as hospital bedspace is often more limited during viral season in pediatric hospitals and PICUs. This information is also important for outpatient asthma providers to consider as they counsel their patients and provide long-term management before and after these hospital stays.
– Commentary by Lisa Ulrich, MD, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Short-Acting Beta-Agonists, Antibiotics, Oral Corticosteroids, and the Associated Burden of COPD
By Mohit Bhutani, MD, FCCP, and colleagues
This study notably highlights the fact that high frequency use of short-acting beta-agonists, antibiotics, and oral corticosteroids may not directly raise the likelihood of an exacerbation but rather may be a sign of worsening disease or poorly managed COPD.
Future studies should investigate the factors that contribute to patients’ frequent prescription use, such as understanding the underlying causes of their exacerbations and other pertinent factors. Additionally, details about patient adherence, a complete clinical history, and the treatment of any further chronic disorders are pivotal for a more complete picture. Enhanced methods for recognizing mild/moderate and severe exacerbations, including patient-reported outcomes, in order to have a better understanding of the influence on drug use and outcomes will be extremely helpful as well. To understand how medications impact results, further studies should look for causal links between medication use and exacerbations.
Lastly, Canadian research on COPD definitely offers insightful information, but when extrapolating these results to the United States, one must take into account variations in the health care system, demographics, and regional patterns along with social determinants of health.
– Commentary by Humayun Anjum, MD, FCCP, Member of the CHEST Physician Editorial Board
Journal CHEST®
By Claire Launois, MD, PhD, and colleagues
It has long been a critique of studies that evaluate the impact of positive airway pressure (PAP) adherence on positive health outcomes that patients who are more adherent to PAP may also be more adherent to other health behaviors that contribute to those positive outcomes, such as incident cardiac events in patients with OSA. An association was found between multiple proxies of the healthy adherer effect and later PAP adherence in patients with OSA, the highest being related to proxies of cardiovascular health. A preceding reduction in health care costs was also found in these patients. These findings may help contribute to interpretation and validation of new studies to help us better understand the impact of PAP treatment of OSA.
– Commentary by Sreelatha Naik, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
By Burton H. Shen, MD, and colleagues
Asthma is a common reason for hospital admission. Between 5% and 35% of patients who are admitted due to asthma are also admitted to the ICU during their hospital stay. For adolescents and young adults, there is variability in admission to the PICU vs adult ICU. This study specifically evaluated patients aged 12 to 26 years old and included hospitals with both a PICU and an adult ICU. The results show us that age, rather than specific clinical characteristics, is the strongest predictor for PICU admission. Patients aged 18 years and younger were more likely to be admitted to the PICU. This is an important consideration, as hospital bedspace is often more limited during viral season in pediatric hospitals and PICUs. This information is also important for outpatient asthma providers to consider as they counsel their patients and provide long-term management before and after these hospital stays.
– Commentary by Lisa Ulrich, MD, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Short-Acting Beta-Agonists, Antibiotics, Oral Corticosteroids, and the Associated Burden of COPD
By Mohit Bhutani, MD, FCCP, and colleagues
This study notably highlights the fact that high frequency use of short-acting beta-agonists, antibiotics, and oral corticosteroids may not directly raise the likelihood of an exacerbation but rather may be a sign of worsening disease or poorly managed COPD.
Future studies should investigate the factors that contribute to patients’ frequent prescription use, such as understanding the underlying causes of their exacerbations and other pertinent factors. Additionally, details about patient adherence, a complete clinical history, and the treatment of any further chronic disorders are pivotal for a more complete picture. Enhanced methods for recognizing mild/moderate and severe exacerbations, including patient-reported outcomes, in order to have a better understanding of the influence on drug use and outcomes will be extremely helpful as well. To understand how medications impact results, further studies should look for causal links between medication use and exacerbations.
Lastly, Canadian research on COPD definitely offers insightful information, but when extrapolating these results to the United States, one must take into account variations in the health care system, demographics, and regional patterns along with social determinants of health.
– Commentary by Humayun Anjum, MD, FCCP, Member of the CHEST Physician Editorial Board
Biomarker use in ARDS resulting from COVID-19 infection
There is renewed interest in the use of immunomodulator therapies in patients with acute hypoxemic respiratory failure.
Beyond COVID-19, studies have also shown corticosteroid therapy improves clinical outcomes in patients with severe community-acquired pneumonia.3 However, the overwhelming majority of studies identifying plasma biomarkers that are associated with clinical outcomes in severe lung injury predate the routine use of corticosteroids.4 Two investigators at Massachusetts General Hospital, Jehan W. Alladina, MD, and George A. Alba, MD, performed a study to assess whether plasma biomarkers previously associated with clinical outcomes in ARDS maintained their predictive value in the setting of widespread immunomodulator therapy in the ICU. Drs. Alladina and Alba are physician-scientists and codirectors of the Program for Advancing Critical Care Translational Science at Massachusetts General Hospital in Boston.
In a study published in CHEST®Critical Care earlier this year, they prospectively enrolled patients with ARDS due to confirmed SARS-CoV-2 infection during the second wave of the COVID-19 pandemic from December 31, 2020, to March 31, 2021, at Massachusetts General Hospital.5 Plasma samples were collected within 24 hours of intubation for mechanical ventilation for protein analysis in 69 patients. Baseline demographics included a mean age of 62 plus or minus 15 years and a BMI of 31 plus or minus 8, and 45% were female. The median PaO2 to FiO2 ratio was 174 mm Hg, consistent with moderate ARDS, and the median duration of ventilation was 17 days. The patients had a median modified sequential organ failure assessment score of 8.5, and in-hospital mortality was 44% by 60 days. Notably, all patients in this cohort received steroids during their ICU stay.
Interestingly, the study investigators found no association between clinical outcomes and circulating proteins implicated in inflammation (eg, interleukin [IL]-6, IL-8), epithelial injury (eg, soluble receptor for advanced glycation end products, surfactant protein D), or coagulation (eg, D-dimer, tissue factor). However, four endothelial biomarkers—von Willebrand factor A2 domain; angiopoietin-2; syndecan-1; and neural precursor cell expressed, developmentally downregulated 9 (NEDD9)—were associated with 60-day mortality after adjusting for age, sex, and severity of illness. A sensitivity analysis, in which patients treated with the IL-6 inhibitor tocilizumab (n=4) were excluded, showed similar results.
Of the endothelial proteins, NEDD9 demonstrated the greatest effect size in its association with mortality in patients with ARDS due to COVID-19 who were treated with immunomodulators. NEDD9 is a scaffolding protein highly expressed in the pulmonary vascular endothelium, but its role in ARDS is not well known. In pulmonary vascular disease, plasma levels are associated with adverse pulmonary hemodynamics and clinical outcomes. Pulmonary artery endothelial NEDD9 is upregulated by cellular hypoxia and can mediate platelet-endothelial adhesion by interacting with P-selectin on the surface of activated platelets.6 Additionally, there is evidence of increased pulmonary endothelial NEDD9 expression and colocalization with fibrin within pulmonary arteries in lung tissue of patients who died from ARDS due to COVID-19.7 Thus, NEDD9 may be an important mediator of pulmonary vascular dysfunction observed in ARDS and could be a novel biomarker for patient subphenotyping and prognostication of clinical outcomes.
In summary, in a cohort of patients with COVID-19 ARDS uniformly treated with corticosteroids, plasma biomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes, but endothelial biomarkers remained prognostic. It is biologically plausible that immunomodulators could attenuate the association between inflammatory biomarkers and patient outcomes. The findings of this study highlight the association of endothelial biomarkers with clinical outcomes in patients with COVID-19 ARDS treated with immunomodulators and warrant prospective validation, especially with the increasing evidence-based use of antiinflammatory therapy in acute lung injury. However, there are several important limitations to consider, including a small sample size from a single institution that precludes any definitive conclusions regarding any negative associations. Moreover, the single time point studied (the day of initiation of mechanical ventilation) and absence of a comparator group do not allow a comprehensive evaluation of the impact of antiinflammatory therapies across the trajectory of disease. Whether the findings are generalizable to all patients with ARDS treated with immunomodulators also remains unknown.
Overall, these data suggest that circulating signatures previously associated with ARDS, particularly those related to systemic inflammation, may have limited prognostic utility in the era of increasing immunomodulator use in critical illness. A deeper understanding of the pathobiology of ARDS, including the complex interplay with systemic immunomodulation, is needed to identify prognostic biomarkers and targeted therapies that improve patient outcomes.
Both authors work in the Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, in Boston.
References
1. Horby P, Lim WS, Emberson JR, et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.
2. Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19. JAMA. 2020;324(13):1-11.
3. Dequin P-F, Meziani F, Quenot J-P, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-1941.
4. Del Valle DM, Kim-Schulze S, Huang H-H, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643.
5. Alladina JW, Giacona FL, Haring AM, et al. Circulating biomarkers of endothelial dysfunction associated with ventilatory ratio and mortality in ARDS resulting from SARS-CoV-2 infection treated with antiinflammatory therapies. CHEST Crit Care. 2024;2(2):100054.
6. Alba GA, Samokhin AO, Wang R-S, et al. NEDD9 is a novel and modifiable mediator of platelet-endothelial adhesion in the pulmonary circulation. Am J Respir Crit Care Med. 2021;203(12):1533-1545.
7. Alba GA, Samokhin AO, Wang R-S, et al. Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS‐CoV‐2 infection. Pulm Circ. 2022;12(2):e12071.
There is renewed interest in the use of immunomodulator therapies in patients with acute hypoxemic respiratory failure.
Beyond COVID-19, studies have also shown corticosteroid therapy improves clinical outcomes in patients with severe community-acquired pneumonia.3 However, the overwhelming majority of studies identifying plasma biomarkers that are associated with clinical outcomes in severe lung injury predate the routine use of corticosteroids.4 Two investigators at Massachusetts General Hospital, Jehan W. Alladina, MD, and George A. Alba, MD, performed a study to assess whether plasma biomarkers previously associated with clinical outcomes in ARDS maintained their predictive value in the setting of widespread immunomodulator therapy in the ICU. Drs. Alladina and Alba are physician-scientists and codirectors of the Program for Advancing Critical Care Translational Science at Massachusetts General Hospital in Boston.
In a study published in CHEST®Critical Care earlier this year, they prospectively enrolled patients with ARDS due to confirmed SARS-CoV-2 infection during the second wave of the COVID-19 pandemic from December 31, 2020, to March 31, 2021, at Massachusetts General Hospital.5 Plasma samples were collected within 24 hours of intubation for mechanical ventilation for protein analysis in 69 patients. Baseline demographics included a mean age of 62 plus or minus 15 years and a BMI of 31 plus or minus 8, and 45% were female. The median PaO2 to FiO2 ratio was 174 mm Hg, consistent with moderate ARDS, and the median duration of ventilation was 17 days. The patients had a median modified sequential organ failure assessment score of 8.5, and in-hospital mortality was 44% by 60 days. Notably, all patients in this cohort received steroids during their ICU stay.
Interestingly, the study investigators found no association between clinical outcomes and circulating proteins implicated in inflammation (eg, interleukin [IL]-6, IL-8), epithelial injury (eg, soluble receptor for advanced glycation end products, surfactant protein D), or coagulation (eg, D-dimer, tissue factor). However, four endothelial biomarkers—von Willebrand factor A2 domain; angiopoietin-2; syndecan-1; and neural precursor cell expressed, developmentally downregulated 9 (NEDD9)—were associated with 60-day mortality after adjusting for age, sex, and severity of illness. A sensitivity analysis, in which patients treated with the IL-6 inhibitor tocilizumab (n=4) were excluded, showed similar results.
Of the endothelial proteins, NEDD9 demonstrated the greatest effect size in its association with mortality in patients with ARDS due to COVID-19 who were treated with immunomodulators. NEDD9 is a scaffolding protein highly expressed in the pulmonary vascular endothelium, but its role in ARDS is not well known. In pulmonary vascular disease, plasma levels are associated with adverse pulmonary hemodynamics and clinical outcomes. Pulmonary artery endothelial NEDD9 is upregulated by cellular hypoxia and can mediate platelet-endothelial adhesion by interacting with P-selectin on the surface of activated platelets.6 Additionally, there is evidence of increased pulmonary endothelial NEDD9 expression and colocalization with fibrin within pulmonary arteries in lung tissue of patients who died from ARDS due to COVID-19.7 Thus, NEDD9 may be an important mediator of pulmonary vascular dysfunction observed in ARDS and could be a novel biomarker for patient subphenotyping and prognostication of clinical outcomes.
In summary, in a cohort of patients with COVID-19 ARDS uniformly treated with corticosteroids, plasma biomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes, but endothelial biomarkers remained prognostic. It is biologically plausible that immunomodulators could attenuate the association between inflammatory biomarkers and patient outcomes. The findings of this study highlight the association of endothelial biomarkers with clinical outcomes in patients with COVID-19 ARDS treated with immunomodulators and warrant prospective validation, especially with the increasing evidence-based use of antiinflammatory therapy in acute lung injury. However, there are several important limitations to consider, including a small sample size from a single institution that precludes any definitive conclusions regarding any negative associations. Moreover, the single time point studied (the day of initiation of mechanical ventilation) and absence of a comparator group do not allow a comprehensive evaluation of the impact of antiinflammatory therapies across the trajectory of disease. Whether the findings are generalizable to all patients with ARDS treated with immunomodulators also remains unknown.
Overall, these data suggest that circulating signatures previously associated with ARDS, particularly those related to systemic inflammation, may have limited prognostic utility in the era of increasing immunomodulator use in critical illness. A deeper understanding of the pathobiology of ARDS, including the complex interplay with systemic immunomodulation, is needed to identify prognostic biomarkers and targeted therapies that improve patient outcomes.
Both authors work in the Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, in Boston.
References
1. Horby P, Lim WS, Emberson JR, et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.
2. Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19. JAMA. 2020;324(13):1-11.
3. Dequin P-F, Meziani F, Quenot J-P, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-1941.
4. Del Valle DM, Kim-Schulze S, Huang H-H, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643.
5. Alladina JW, Giacona FL, Haring AM, et al. Circulating biomarkers of endothelial dysfunction associated with ventilatory ratio and mortality in ARDS resulting from SARS-CoV-2 infection treated with antiinflammatory therapies. CHEST Crit Care. 2024;2(2):100054.
6. Alba GA, Samokhin AO, Wang R-S, et al. NEDD9 is a novel and modifiable mediator of platelet-endothelial adhesion in the pulmonary circulation. Am J Respir Crit Care Med. 2021;203(12):1533-1545.
7. Alba GA, Samokhin AO, Wang R-S, et al. Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS‐CoV‐2 infection. Pulm Circ. 2022;12(2):e12071.
There is renewed interest in the use of immunomodulator therapies in patients with acute hypoxemic respiratory failure.
Beyond COVID-19, studies have also shown corticosteroid therapy improves clinical outcomes in patients with severe community-acquired pneumonia.3 However, the overwhelming majority of studies identifying plasma biomarkers that are associated with clinical outcomes in severe lung injury predate the routine use of corticosteroids.4 Two investigators at Massachusetts General Hospital, Jehan W. Alladina, MD, and George A. Alba, MD, performed a study to assess whether plasma biomarkers previously associated with clinical outcomes in ARDS maintained their predictive value in the setting of widespread immunomodulator therapy in the ICU. Drs. Alladina and Alba are physician-scientists and codirectors of the Program for Advancing Critical Care Translational Science at Massachusetts General Hospital in Boston.
In a study published in CHEST®Critical Care earlier this year, they prospectively enrolled patients with ARDS due to confirmed SARS-CoV-2 infection during the second wave of the COVID-19 pandemic from December 31, 2020, to March 31, 2021, at Massachusetts General Hospital.5 Plasma samples were collected within 24 hours of intubation for mechanical ventilation for protein analysis in 69 patients. Baseline demographics included a mean age of 62 plus or minus 15 years and a BMI of 31 plus or minus 8, and 45% were female. The median PaO2 to FiO2 ratio was 174 mm Hg, consistent with moderate ARDS, and the median duration of ventilation was 17 days. The patients had a median modified sequential organ failure assessment score of 8.5, and in-hospital mortality was 44% by 60 days. Notably, all patients in this cohort received steroids during their ICU stay.
Interestingly, the study investigators found no association between clinical outcomes and circulating proteins implicated in inflammation (eg, interleukin [IL]-6, IL-8), epithelial injury (eg, soluble receptor for advanced glycation end products, surfactant protein D), or coagulation (eg, D-dimer, tissue factor). However, four endothelial biomarkers—von Willebrand factor A2 domain; angiopoietin-2; syndecan-1; and neural precursor cell expressed, developmentally downregulated 9 (NEDD9)—were associated with 60-day mortality after adjusting for age, sex, and severity of illness. A sensitivity analysis, in which patients treated with the IL-6 inhibitor tocilizumab (n=4) were excluded, showed similar results.
Of the endothelial proteins, NEDD9 demonstrated the greatest effect size in its association with mortality in patients with ARDS due to COVID-19 who were treated with immunomodulators. NEDD9 is a scaffolding protein highly expressed in the pulmonary vascular endothelium, but its role in ARDS is not well known. In pulmonary vascular disease, plasma levels are associated with adverse pulmonary hemodynamics and clinical outcomes. Pulmonary artery endothelial NEDD9 is upregulated by cellular hypoxia and can mediate platelet-endothelial adhesion by interacting with P-selectin on the surface of activated platelets.6 Additionally, there is evidence of increased pulmonary endothelial NEDD9 expression and colocalization with fibrin within pulmonary arteries in lung tissue of patients who died from ARDS due to COVID-19.7 Thus, NEDD9 may be an important mediator of pulmonary vascular dysfunction observed in ARDS and could be a novel biomarker for patient subphenotyping and prognostication of clinical outcomes.
In summary, in a cohort of patients with COVID-19 ARDS uniformly treated with corticosteroids, plasma biomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes, but endothelial biomarkers remained prognostic. It is biologically plausible that immunomodulators could attenuate the association between inflammatory biomarkers and patient outcomes. The findings of this study highlight the association of endothelial biomarkers with clinical outcomes in patients with COVID-19 ARDS treated with immunomodulators and warrant prospective validation, especially with the increasing evidence-based use of antiinflammatory therapy in acute lung injury. However, there are several important limitations to consider, including a small sample size from a single institution that precludes any definitive conclusions regarding any negative associations. Moreover, the single time point studied (the day of initiation of mechanical ventilation) and absence of a comparator group do not allow a comprehensive evaluation of the impact of antiinflammatory therapies across the trajectory of disease. Whether the findings are generalizable to all patients with ARDS treated with immunomodulators also remains unknown.
Overall, these data suggest that circulating signatures previously associated with ARDS, particularly those related to systemic inflammation, may have limited prognostic utility in the era of increasing immunomodulator use in critical illness. A deeper understanding of the pathobiology of ARDS, including the complex interplay with systemic immunomodulation, is needed to identify prognostic biomarkers and targeted therapies that improve patient outcomes.
Both authors work in the Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, in Boston.
References
1. Horby P, Lim WS, Emberson JR, et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.
2. Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19. JAMA. 2020;324(13):1-11.
3. Dequin P-F, Meziani F, Quenot J-P, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-1941.
4. Del Valle DM, Kim-Schulze S, Huang H-H, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643.
5. Alladina JW, Giacona FL, Haring AM, et al. Circulating biomarkers of endothelial dysfunction associated with ventilatory ratio and mortality in ARDS resulting from SARS-CoV-2 infection treated with antiinflammatory therapies. CHEST Crit Care. 2024;2(2):100054.
6. Alba GA, Samokhin AO, Wang R-S, et al. NEDD9 is a novel and modifiable mediator of platelet-endothelial adhesion in the pulmonary circulation. Am J Respir Crit Care Med. 2021;203(12):1533-1545.
7. Alba GA, Samokhin AO, Wang R-S, et al. Pulmonary endothelial NEDD9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to SARS‐CoV‐2 infection. Pulm Circ. 2022;12(2):e12071.
Improved CHEST Physician® coming in 2025
FROM THE CHEST PHYSICIAN EDITORIAL BOARD – There will be some exciting changes happening at the CHEST Physician publication in 2025. We’re building on nearly three decades as a leading source of news and clinical commentary in pulmonary and critical care medicine to roll out several notable improvements.
First, the CHEST Physician website, chestphysician.org, will undergo a complete transformation. With an improved user experience, you’ll be able to more easily find content relevant to your interests and specialties.
Second, a brand-new email newsletter will hit your inbox twice a month, starting in January 2025. These emails will give you a quick look into timely content that may interest you and affect your daily practice. Additionally, this digital-first approach will get you the news and research you rely on sooner.
Lastly, the redesigned CHEST Physician print issue will now be produced and delivered on a quarterly basis. The first issue will arrive in March 2025. These special issues will feature print-exclusive content and graphics, as well as offer a deeper dive into the most relevant news stories from recent months.
Notably, all new CHEST Physician content published in the new year will be tailored to our audience and readership, and it will address the issues and topics that matter to you most as health care providers.
As the CHEST Physician publication undergoes this transformation, we want to hear from you. What topics do you want more of? How can CHEST continue to best serve the chest medicine community? Email [email protected] to share your ideas.
Thank you for being a loyal CHEST Physician reader. We look forward to bringing you elevated content and an enhanced reader experience in the new year.
FROM THE CHEST PHYSICIAN EDITORIAL BOARD – There will be some exciting changes happening at the CHEST Physician publication in 2025. We’re building on nearly three decades as a leading source of news and clinical commentary in pulmonary and critical care medicine to roll out several notable improvements.
First, the CHEST Physician website, chestphysician.org, will undergo a complete transformation. With an improved user experience, you’ll be able to more easily find content relevant to your interests and specialties.
Second, a brand-new email newsletter will hit your inbox twice a month, starting in January 2025. These emails will give you a quick look into timely content that may interest you and affect your daily practice. Additionally, this digital-first approach will get you the news and research you rely on sooner.
Lastly, the redesigned CHEST Physician print issue will now be produced and delivered on a quarterly basis. The first issue will arrive in March 2025. These special issues will feature print-exclusive content and graphics, as well as offer a deeper dive into the most relevant news stories from recent months.
Notably, all new CHEST Physician content published in the new year will be tailored to our audience and readership, and it will address the issues and topics that matter to you most as health care providers.
As the CHEST Physician publication undergoes this transformation, we want to hear from you. What topics do you want more of? How can CHEST continue to best serve the chest medicine community? Email [email protected] to share your ideas.
Thank you for being a loyal CHEST Physician reader. We look forward to bringing you elevated content and an enhanced reader experience in the new year.
FROM THE CHEST PHYSICIAN EDITORIAL BOARD – There will be some exciting changes happening at the CHEST Physician publication in 2025. We’re building on nearly three decades as a leading source of news and clinical commentary in pulmonary and critical care medicine to roll out several notable improvements.
First, the CHEST Physician website, chestphysician.org, will undergo a complete transformation. With an improved user experience, you’ll be able to more easily find content relevant to your interests and specialties.
Second, a brand-new email newsletter will hit your inbox twice a month, starting in January 2025. These emails will give you a quick look into timely content that may interest you and affect your daily practice. Additionally, this digital-first approach will get you the news and research you rely on sooner.
Lastly, the redesigned CHEST Physician print issue will now be produced and delivered on a quarterly basis. The first issue will arrive in March 2025. These special issues will feature print-exclusive content and graphics, as well as offer a deeper dive into the most relevant news stories from recent months.
Notably, all new CHEST Physician content published in the new year will be tailored to our audience and readership, and it will address the issues and topics that matter to you most as health care providers.
As the CHEST Physician publication undergoes this transformation, we want to hear from you. What topics do you want more of? How can CHEST continue to best serve the chest medicine community? Email [email protected] to share your ideas.
Thank you for being a loyal CHEST Physician reader. We look forward to bringing you elevated content and an enhanced reader experience in the new year.
Should the Body Roundness Index Replace BMI?
In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism.
According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
Studies Support BRI
Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.
A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
Why Replace BMI?
Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”
Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
BMI Classifies Bodybuilders as Obese
The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:
BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass.
BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example.
In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.
The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:
BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)
In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
Could BRI Replace BMI?
Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.
Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.
However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.
Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
Anthropometric Measures Only for Clinical Use
Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.
“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”
Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.
He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”
Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
The BMI Might Be Responsible for the ‘Healthy Obese’
One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.
According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.
Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.
“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
This story was translated from Medscape’s German edition 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.
In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism.
According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
Studies Support BRI
Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.
A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
Why Replace BMI?
Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”
Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
BMI Classifies Bodybuilders as Obese
The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:
BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass.
BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example.
In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.
The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:
BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)
In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
Could BRI Replace BMI?
Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.
Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.
However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.
Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
Anthropometric Measures Only for Clinical Use
Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.
“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”
Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.
He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”
Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
The BMI Might Be Responsible for the ‘Healthy Obese’
One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.
According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.
Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.
“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
This story was translated from Medscape’s German edition 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.
In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism.
According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
Studies Support BRI
Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.
A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
Why Replace BMI?
Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”
Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
BMI Classifies Bodybuilders as Obese
The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:
BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass.
BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example.
In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.
The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:
BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)
In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
Could BRI Replace BMI?
Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.
Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.
However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.
Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
Anthropometric Measures Only for Clinical Use
Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.
“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”
Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.
He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”
Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
The BMI Might Be Responsible for the ‘Healthy Obese’
One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.
According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.
Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.
“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
This story was translated from Medscape’s German edition 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.
Know the Ins and Outs of Prescribing Obesity Medications in Pediatric Patients
ORLANDO, FLORIDA — The rationale for using obesity medications in pediatric patients is that it’s using “a biological intervention to treat a biologically based disease,” according to Claudia Fox, MD, MPH, an associate professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota, Minneapolis. At the annual meeting of the American Academy of Pediatrics (AAP), Fox provided
“This field is changing so rapidly that even over the course of the last 3 or 4 months, the verbiage around what we should be calling these interventions has changed,” Fox noted. Instead of “anti-obesity” medications, “most of us are now using the term obesity medications to highlight or to reduce chances of stigma and bias that can come along with this topic.”
Jessica Ivers, MD, a pediatrician at Swedish Pediatrics in Seattle, Washington, said she found the session very informative, particularly because she doesn’t think many pediatricians currently feel very comfortable prescribing obesity medications.
“It answered questions that any general pediatrician would have, and it’s kind of a new field that people are learning about,” Ivers said. “I think we just need more education. It’s just too new, and people haven’t had the education and the support from colleagues to [use the medications].”
Fox first reminded attendees of precisely what obesity is: A chronic, relapsing, multifactorial, neurobehavioral disease that involves the accumulation and/or distribution of excess body fat that results in impaired health. AAP clinical practice guidelines currently advise that youth aged 12 years or older who have obesity be offered weight loss pharmacotherapy as an adjunct to lifestyle treatment, taking into consideration the indications, risks, and benefits of each medication.
That doesn’t necessarily mean every child aged 12 years or older with a body mass index (BMI) of at least the 95th percentile should be prescribed one of these medications, Fox said. But pediatricians should start becoming familiar with the options and recognize that part of reducing the stigma of this disease is emphasizing that these medications are prescribed not for “weight loss” but to treat the disease of obesity, Fox said. The guidelines advise “early, intensive care” and focusing on the whole child, “using a family-centered and nonstigmatizing approach that acknowledges obesity’s biologic, social, and structural drivers.”
Offer the Full Spectrum of Care Early On
Early intervention means starting obesity treatment at diagnosis, without watchful waiting or the previously recommended staged approach. Instead of trying lifestyle therapy for 3-6 months, then considering the addition of medication, and then considering bariatric surgery, “we should be offering the full spectrum of obesity care as appropriate for that individual patient,” Fox said.
Some children with severe obesity may need the combination of lifestyle therapy and pharmacotherapy right up front, whereas another might be able to try lifestyle therapy alone for a while first. “What we know is that, for most interventions, whether it is lifestyle therapy, a medication, or bariatric surgery, early response typically predicts longer-term response,” Fox said. A study conducted by her group, for example, found that a 3% BMI reduction after 1 month with lifestyle therapy was very predictive of clinically meaningful BMI reduction at 1 year.
As with any medical treatment, physicians need to weigh the risks of the medication — short-term side effects and unknown long-term risks (or benefits) — against the risks of not treating. Because obesity is a progressive disease, “if we don’t treat it, most will develop comorbid conditions, or worsening of their already present comorbid conditions, and this does indeed lead to shortened life expectancy,” Fox said. Those who should be treated with medication are obviously those in whom the benefits outweigh the risks, Fox said, which depends on their age, their comorbidities, the severity of obesity, and the safety and efficacy of medication options.
“If I have a patient who has maybe class 2 obesity but no other comorbid conditions, I may be less inclined to start an obesity medication than a kid who has class 1 obesity and obstructive sleep apnea, for instance,” Fox said. “Some of the medications are very, very potent and effective. If you have a kid who maybe has less severe forms of obesity, perhaps they don’t need something that’s so potent.”
BMI trajectory is also a factor to consider. She said she may not be too concerned about a 16-year-old who has always been at the 95th percentile and is otherwise healthy, but the situation is different for a 16-year-old who used to be in the 25th percentile and has rapidly progressed to the 50th and then 75th percentiles in a trajectory heading straight up.
Another factor that may come into play is the patient and family preferences, though Fox noted that weight bias and stigma often interfere here. If obesity medications are brought up, the family may bring up the need for more exercise and better meal prep at home.
“They have this sense that they just need to try harder, that if they did that, the obesity would somehow get better on its own,” Fox said. “That’s an internalized bias that it’s somehow their fault, rather than realizing that this is indeed a biological disorder.”
Finally, clinicians may want to consider the child’s response to lifestyle therapy and whether they have already had bariatric surgery because these medications can be prescribed in people who did not have an adequate response to surgery.
Overview of the Medications
There are currently six obesity medications approved by the Food and Drug Administration (FDA) for use in youth: Phentermine, orlistat, liraglutide, phentermine/topiramate, semaglutide, and setmelanotide.
Of these, orlistat is rarely used now because it results in the least amount of change in BMI (about a 3% loss change in BMI), has a lot of gastrointestinal side effects, often is not covered by insurance, and is expensive out of pocket. Setmelanotide is indicated only in those aged 6 years or older who have obesity because of Bardet-Biedl syndrome or one of three other rare genetic conditions: a POMC, LEPR, or PCSK1 deficiency. Fox therefore focused on the other medications besides these two.
While nearly all the currently available obesity medications are only approved in those aged 12 years or older, Fox noted that studies are ongoing at younger ages, so some of these medications may receive approval in younger populations in the future. The only one currently available for a younger age is liraglutide, which is approved down to 6 years old in children with type 2 diabetes.
“Very young kids who have very severe forms of obesity need intervention, and unfortunately, at this point, we really don’t have much to offer them,” Fox said.
Fox highlighted six key factors to consider in selecting a medication for those aged 12 years or older, though one of these, in the US healthcare system, can tend to trump all the others. Those factors are mechanism of action, side effect profile, effects on other diagnoses, patient/family preferences, provider comfort, and finally — the potentially overruling one — insurance coverage and access.
“These days, insurance coverage and access are really the No. 1 driver when I’m seeing a patient,” Fox said. “The first thing I do is look at their insurance and then also look at what kind of updates our pharmacist has given us about which medication is currently in stock.”
Each medication has different properties that should be considered with the child’s health profile. For example, topiramate is a carbonic anhydrase inhibitor so likely shouldn’t be prescribed in a child who is taking any other carbonic anhydrase inhibitor. Fox said she probably wouldn’t prescribe phentermine in a child with severe anxiety because it might enhance the anxiety effect. But if a child has migraines, she may be more inclined to try phentermine/topiramate first because the topiramate may help with the migraines. Similarly, if a child has type 2 diabetes or prediabetes, she may lean toward one of the glucagon-like peptide 1 (GLP-1) agonist drugs.
Liraglutide and Semaglutide
Liraglutide and semaglutide are both GLP-1 receptor agonists administered subcutaneously to reduce appetite, increase satiety, slow gastric emptying, and reduce the food reward response in the brain. Liraglutide can result in up to 4.5%-5% change in BMI, and semaglutide, the most potent of all the medications, can result in up to a 17% change in BMI.
Liraglutide and semaglutide are both approved for patients aged 12 years or older who weigh at least 60 kg and have a BMI of at least the 95th percentile. Liraglutide is also approved for those aged 10 years or older with type 2 diabetes. Both are contraindicated in those with a family history of medullary thyroid cancer or multiple endocrine neoplasia II. The risks to watch for include pancreatitis and gallbladder disease. Also keep in mind if you have a patient with type 1 diabetes and insulin resistance; prescribing a GLP-1 agonist is appropriate, but their insulin needs will decrease, necessitating close monitoring of their blood glucose, Fox noted.
These GLP-1 medications can be considered for those who have insurance coverage for them, who have diabetes or prediabetes, who are comfortable with daily (liraglutide) or weekly (semaglutide) injections, who have food cravings, and who have poor satiety or satiation. Without insurance, these medications are very expensive.
The most common side effects include injection site reactions and nausea, vomiting, and diarrhea, though all these usually fade and can be minimized with small portions and slower eating if needed. Less common possible side effects can include abdominal pain, constipation, headache, dizziness, fatigue, and hypoglycemia. If patients develop severe belly pain that radiates to their back, they should be assessed for pancreatitis.
It’s also important to demonstrate for patients how to do the injections, Fox said. Liraglutide dosing begins at 0.6 mg daily for a week, followed by a week at 1.2 mg, a week at 1.8 mg, a week at 2.4 mg, and then 3 mg daily. Semaglutide dosing starts at 0.25 mg weekly for 4 weeks, then going up each subsequent month as needed to 0.5 mg, then 1 mg, then 1.7 mg, and finally 2.4 mg. Though there’s no standard follow-up schedule for these medications, Fox suggested considering monthly visits for the first 3 months and then every 2-3 months to assess heart rate and blood pressure, the injection site, adherence, side effects, and the effect on BMI and eating.
“Are they getting appetite suppression, but not too much appetite suppression?” Fox said. “Just like in eating disorder treatment, we want our patients to eat regularly spaced meals. If their appetite is so suppressed that they are hardly eating anything, that’s a problem.”
Fox also offered the following additional pearls about these medications:
- Though manufacturers have struggled to keep up with demand, the shortages of these medications are improving. However, beware the compounding pharmacies filling the gap because compounded medications are not FDA approved, and quality control issues are a concern.
- Prior authorizations are usually needed, and common reasons for denial to anticipate include lack of documentation on not having contraindications, the patient not following a low-calorie diet or engaging in physical activity, and the patient not having seen a registered dietitian.
- Patients should expect gastrointestinal side effects, but ondansetron can be prescribed to lessen the intensity.
Phentermine/Topiramate
Phentermine/topiramate extended-release is a once-daily oral tablet, with the phentermine acting to reduce appetite (by simulating the release of norepinephrine) and the topiramate reducing caloric intake and food reward response (by increasing gamma-aminobutyric acid activity). It’s approved for those aged 12 years or older with a BMI of at least the 95th percentile and should be considered in those with strong hunger, low energy, binge eating disorder, or migraines, as well as those who have insurance coverage for it. It can result in up to a 10% change in BMI.
Contraindications include pregnancy, substance use, cardiovascular disease (though it’s okay in patients with controlled hypertension), hyperthyroidism, glaucoma, and monoamine oxidase inhibitor (MAOI) use. Fox emphasized the teratogenic effects, so patients capable of pregnancy need to be on reliable birth control. The most common side effects include paresthesia, dizziness, dysgeusia, insomnia, and constipation.
A risk of topiramate is kidney stones, so patients should drink a lot of water, especially in hot weather, Fox said. Other risks can include metabolic acidosis, suicidality, poor cognitive function, high blood pressure, and renal impairment.
“If your patient is struggling academically, I might use this medication a bit more cautiously, particularly when the dose gets above 100 mg a day,” Fox said. “That’s when the cognitive effects tend to emerge more strongly.”
Patients with congenital heart disease should meet with their cardiologist before starting this medication, and although patients taking selective serotonin reuptake inhibitors (SSRIs) can take this, there is a potential increased risk for serotonin syndrome because phentermine has a little bit of serotonergic activity, she said.
Before prescribing, do an exam to ensure the patient doesn’t have a heart murmur, isn’t hypertensive, isn’t pregnant, has normal kidney function, and has bicarbonate in a reasonable range. Dosing begins with a daily 3.75/23-mg capsule for 2 weeks, followed by 2 weeks at 7.5 mg/46 mg. As with the GLP-1 drugs, Fox advises considering monthly follow-ups for the first 3 months and then visits every 2-3 months. Each visit should include the assessment of cardiovascular health, heart rate, blood pressure, side effects, pregnancy risk, and the medication’s effect on BMI and eating. If the patient is tolerating a dose of 7.5 mg/46 mg, it can be increased to 11.25 mg/69 mg for 2 weeks and then to 15 mg/92 mg. Bicarbonate and creatinine should be checked every 6-12 months; if bicarbonate < 18 mEq/L, the dose should be reduced and then bicarbonate should be checked again a month later.
Fox noted that this drug is expected to go off patent in late 2024 or in 2025, which will substantially reduce the cost. It’s also possible to prescribe phentermine and topiramate separately, which may reduce costs or help with insurance coverage and can allow for evening dosing of topiramate.
Phentermine
Phentermine alone is only approved for those older than 16 years who have a BMI of at least 30, or at least 27 with weight-related comorbidities, and it’s not approved for use longer than 12 weeks. It results in a BMI change of up to 5%. It should be considered in those with strong hunger and low energy and in those who don’t have adequate insurance coverage because out-of-pocket costs can be as little as $5/mo.
Contraindications are the same as those for the combined pill above: Substance use, cardiovascular disease, hyperthyroidism, glaucoma, MAOI use, and agitation. Again, take caution with patients who have hypertension, have congenital heart disease, or take SSRIs or insulin.
Side effects can include palpitations, tachycardia, dry mouth, headache, insomnia, and anxiety. The dose starts at 15 mg daily, and Fox advises following a similar follow-up as with the other medications, at which clinicians should assess BMI, the medication’s effect on eating, cardiovascular health, and side effects and have a discussion about off-label use. Off-label use refers to prescriptions lasting longer than 12 weeks, but it’s arguably safer than attention-deficit/hyperactivity disorder stimulants because of the lower addiction potential, Fox said.
What Else to Know
Because obesity is a chronic disease, treatment will be ongoing, Fox noted. A lot of people will ask when or where the “off-ramp” for these medications is, but many people will need these medications long term just as someone with other chronic diseases requires lifetime pharmacotherapy. The treatment intensity will vary based on disease severity and individual characteristics, Fox said.
For those feeling overwhelmed by the options, Fox advises clinicians to start by picking one medication to learn and then spending the time to read the FDA package insert in full. Get samples and then closely follow patients to learn that medication well before moving on to learn another. She also noted the opportunity for pediatricians to see a pediatric obesity medicine fellowship.
No external funding was used for the presentation. Fox is a site principal investigator for clinical trials sponsored by Novo Nordisk and Eli Lilly. Ivers had no disclosures.
A version of this article first appeared on Medscape.com.
ORLANDO, FLORIDA — The rationale for using obesity medications in pediatric patients is that it’s using “a biological intervention to treat a biologically based disease,” according to Claudia Fox, MD, MPH, an associate professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota, Minneapolis. At the annual meeting of the American Academy of Pediatrics (AAP), Fox provided
“This field is changing so rapidly that even over the course of the last 3 or 4 months, the verbiage around what we should be calling these interventions has changed,” Fox noted. Instead of “anti-obesity” medications, “most of us are now using the term obesity medications to highlight or to reduce chances of stigma and bias that can come along with this topic.”
Jessica Ivers, MD, a pediatrician at Swedish Pediatrics in Seattle, Washington, said she found the session very informative, particularly because she doesn’t think many pediatricians currently feel very comfortable prescribing obesity medications.
“It answered questions that any general pediatrician would have, and it’s kind of a new field that people are learning about,” Ivers said. “I think we just need more education. It’s just too new, and people haven’t had the education and the support from colleagues to [use the medications].”
Fox first reminded attendees of precisely what obesity is: A chronic, relapsing, multifactorial, neurobehavioral disease that involves the accumulation and/or distribution of excess body fat that results in impaired health. AAP clinical practice guidelines currently advise that youth aged 12 years or older who have obesity be offered weight loss pharmacotherapy as an adjunct to lifestyle treatment, taking into consideration the indications, risks, and benefits of each medication.
That doesn’t necessarily mean every child aged 12 years or older with a body mass index (BMI) of at least the 95th percentile should be prescribed one of these medications, Fox said. But pediatricians should start becoming familiar with the options and recognize that part of reducing the stigma of this disease is emphasizing that these medications are prescribed not for “weight loss” but to treat the disease of obesity, Fox said. The guidelines advise “early, intensive care” and focusing on the whole child, “using a family-centered and nonstigmatizing approach that acknowledges obesity’s biologic, social, and structural drivers.”
Offer the Full Spectrum of Care Early On
Early intervention means starting obesity treatment at diagnosis, without watchful waiting or the previously recommended staged approach. Instead of trying lifestyle therapy for 3-6 months, then considering the addition of medication, and then considering bariatric surgery, “we should be offering the full spectrum of obesity care as appropriate for that individual patient,” Fox said.
Some children with severe obesity may need the combination of lifestyle therapy and pharmacotherapy right up front, whereas another might be able to try lifestyle therapy alone for a while first. “What we know is that, for most interventions, whether it is lifestyle therapy, a medication, or bariatric surgery, early response typically predicts longer-term response,” Fox said. A study conducted by her group, for example, found that a 3% BMI reduction after 1 month with lifestyle therapy was very predictive of clinically meaningful BMI reduction at 1 year.
As with any medical treatment, physicians need to weigh the risks of the medication — short-term side effects and unknown long-term risks (or benefits) — against the risks of not treating. Because obesity is a progressive disease, “if we don’t treat it, most will develop comorbid conditions, or worsening of their already present comorbid conditions, and this does indeed lead to shortened life expectancy,” Fox said. Those who should be treated with medication are obviously those in whom the benefits outweigh the risks, Fox said, which depends on their age, their comorbidities, the severity of obesity, and the safety and efficacy of medication options.
“If I have a patient who has maybe class 2 obesity but no other comorbid conditions, I may be less inclined to start an obesity medication than a kid who has class 1 obesity and obstructive sleep apnea, for instance,” Fox said. “Some of the medications are very, very potent and effective. If you have a kid who maybe has less severe forms of obesity, perhaps they don’t need something that’s so potent.”
BMI trajectory is also a factor to consider. She said she may not be too concerned about a 16-year-old who has always been at the 95th percentile and is otherwise healthy, but the situation is different for a 16-year-old who used to be in the 25th percentile and has rapidly progressed to the 50th and then 75th percentiles in a trajectory heading straight up.
Another factor that may come into play is the patient and family preferences, though Fox noted that weight bias and stigma often interfere here. If obesity medications are brought up, the family may bring up the need for more exercise and better meal prep at home.
“They have this sense that they just need to try harder, that if they did that, the obesity would somehow get better on its own,” Fox said. “That’s an internalized bias that it’s somehow their fault, rather than realizing that this is indeed a biological disorder.”
Finally, clinicians may want to consider the child’s response to lifestyle therapy and whether they have already had bariatric surgery because these medications can be prescribed in people who did not have an adequate response to surgery.
Overview of the Medications
There are currently six obesity medications approved by the Food and Drug Administration (FDA) for use in youth: Phentermine, orlistat, liraglutide, phentermine/topiramate, semaglutide, and setmelanotide.
Of these, orlistat is rarely used now because it results in the least amount of change in BMI (about a 3% loss change in BMI), has a lot of gastrointestinal side effects, often is not covered by insurance, and is expensive out of pocket. Setmelanotide is indicated only in those aged 6 years or older who have obesity because of Bardet-Biedl syndrome or one of three other rare genetic conditions: a POMC, LEPR, or PCSK1 deficiency. Fox therefore focused on the other medications besides these two.
While nearly all the currently available obesity medications are only approved in those aged 12 years or older, Fox noted that studies are ongoing at younger ages, so some of these medications may receive approval in younger populations in the future. The only one currently available for a younger age is liraglutide, which is approved down to 6 years old in children with type 2 diabetes.
“Very young kids who have very severe forms of obesity need intervention, and unfortunately, at this point, we really don’t have much to offer them,” Fox said.
Fox highlighted six key factors to consider in selecting a medication for those aged 12 years or older, though one of these, in the US healthcare system, can tend to trump all the others. Those factors are mechanism of action, side effect profile, effects on other diagnoses, patient/family preferences, provider comfort, and finally — the potentially overruling one — insurance coverage and access.
“These days, insurance coverage and access are really the No. 1 driver when I’m seeing a patient,” Fox said. “The first thing I do is look at their insurance and then also look at what kind of updates our pharmacist has given us about which medication is currently in stock.”
Each medication has different properties that should be considered with the child’s health profile. For example, topiramate is a carbonic anhydrase inhibitor so likely shouldn’t be prescribed in a child who is taking any other carbonic anhydrase inhibitor. Fox said she probably wouldn’t prescribe phentermine in a child with severe anxiety because it might enhance the anxiety effect. But if a child has migraines, she may be more inclined to try phentermine/topiramate first because the topiramate may help with the migraines. Similarly, if a child has type 2 diabetes or prediabetes, she may lean toward one of the glucagon-like peptide 1 (GLP-1) agonist drugs.
Liraglutide and Semaglutide
Liraglutide and semaglutide are both GLP-1 receptor agonists administered subcutaneously to reduce appetite, increase satiety, slow gastric emptying, and reduce the food reward response in the brain. Liraglutide can result in up to 4.5%-5% change in BMI, and semaglutide, the most potent of all the medications, can result in up to a 17% change in BMI.
Liraglutide and semaglutide are both approved for patients aged 12 years or older who weigh at least 60 kg and have a BMI of at least the 95th percentile. Liraglutide is also approved for those aged 10 years or older with type 2 diabetes. Both are contraindicated in those with a family history of medullary thyroid cancer or multiple endocrine neoplasia II. The risks to watch for include pancreatitis and gallbladder disease. Also keep in mind if you have a patient with type 1 diabetes and insulin resistance; prescribing a GLP-1 agonist is appropriate, but their insulin needs will decrease, necessitating close monitoring of their blood glucose, Fox noted.
These GLP-1 medications can be considered for those who have insurance coverage for them, who have diabetes or prediabetes, who are comfortable with daily (liraglutide) or weekly (semaglutide) injections, who have food cravings, and who have poor satiety or satiation. Without insurance, these medications are very expensive.
The most common side effects include injection site reactions and nausea, vomiting, and diarrhea, though all these usually fade and can be minimized with small portions and slower eating if needed. Less common possible side effects can include abdominal pain, constipation, headache, dizziness, fatigue, and hypoglycemia. If patients develop severe belly pain that radiates to their back, they should be assessed for pancreatitis.
It’s also important to demonstrate for patients how to do the injections, Fox said. Liraglutide dosing begins at 0.6 mg daily for a week, followed by a week at 1.2 mg, a week at 1.8 mg, a week at 2.4 mg, and then 3 mg daily. Semaglutide dosing starts at 0.25 mg weekly for 4 weeks, then going up each subsequent month as needed to 0.5 mg, then 1 mg, then 1.7 mg, and finally 2.4 mg. Though there’s no standard follow-up schedule for these medications, Fox suggested considering monthly visits for the first 3 months and then every 2-3 months to assess heart rate and blood pressure, the injection site, adherence, side effects, and the effect on BMI and eating.
“Are they getting appetite suppression, but not too much appetite suppression?” Fox said. “Just like in eating disorder treatment, we want our patients to eat regularly spaced meals. If their appetite is so suppressed that they are hardly eating anything, that’s a problem.”
Fox also offered the following additional pearls about these medications:
- Though manufacturers have struggled to keep up with demand, the shortages of these medications are improving. However, beware the compounding pharmacies filling the gap because compounded medications are not FDA approved, and quality control issues are a concern.
- Prior authorizations are usually needed, and common reasons for denial to anticipate include lack of documentation on not having contraindications, the patient not following a low-calorie diet or engaging in physical activity, and the patient not having seen a registered dietitian.
- Patients should expect gastrointestinal side effects, but ondansetron can be prescribed to lessen the intensity.
Phentermine/Topiramate
Phentermine/topiramate extended-release is a once-daily oral tablet, with the phentermine acting to reduce appetite (by simulating the release of norepinephrine) and the topiramate reducing caloric intake and food reward response (by increasing gamma-aminobutyric acid activity). It’s approved for those aged 12 years or older with a BMI of at least the 95th percentile and should be considered in those with strong hunger, low energy, binge eating disorder, or migraines, as well as those who have insurance coverage for it. It can result in up to a 10% change in BMI.
Contraindications include pregnancy, substance use, cardiovascular disease (though it’s okay in patients with controlled hypertension), hyperthyroidism, glaucoma, and monoamine oxidase inhibitor (MAOI) use. Fox emphasized the teratogenic effects, so patients capable of pregnancy need to be on reliable birth control. The most common side effects include paresthesia, dizziness, dysgeusia, insomnia, and constipation.
A risk of topiramate is kidney stones, so patients should drink a lot of water, especially in hot weather, Fox said. Other risks can include metabolic acidosis, suicidality, poor cognitive function, high blood pressure, and renal impairment.
“If your patient is struggling academically, I might use this medication a bit more cautiously, particularly when the dose gets above 100 mg a day,” Fox said. “That’s when the cognitive effects tend to emerge more strongly.”
Patients with congenital heart disease should meet with their cardiologist before starting this medication, and although patients taking selective serotonin reuptake inhibitors (SSRIs) can take this, there is a potential increased risk for serotonin syndrome because phentermine has a little bit of serotonergic activity, she said.
Before prescribing, do an exam to ensure the patient doesn’t have a heart murmur, isn’t hypertensive, isn’t pregnant, has normal kidney function, and has bicarbonate in a reasonable range. Dosing begins with a daily 3.75/23-mg capsule for 2 weeks, followed by 2 weeks at 7.5 mg/46 mg. As with the GLP-1 drugs, Fox advises considering monthly follow-ups for the first 3 months and then visits every 2-3 months. Each visit should include the assessment of cardiovascular health, heart rate, blood pressure, side effects, pregnancy risk, and the medication’s effect on BMI and eating. If the patient is tolerating a dose of 7.5 mg/46 mg, it can be increased to 11.25 mg/69 mg for 2 weeks and then to 15 mg/92 mg. Bicarbonate and creatinine should be checked every 6-12 months; if bicarbonate < 18 mEq/L, the dose should be reduced and then bicarbonate should be checked again a month later.
Fox noted that this drug is expected to go off patent in late 2024 or in 2025, which will substantially reduce the cost. It’s also possible to prescribe phentermine and topiramate separately, which may reduce costs or help with insurance coverage and can allow for evening dosing of topiramate.
Phentermine
Phentermine alone is only approved for those older than 16 years who have a BMI of at least 30, or at least 27 with weight-related comorbidities, and it’s not approved for use longer than 12 weeks. It results in a BMI change of up to 5%. It should be considered in those with strong hunger and low energy and in those who don’t have adequate insurance coverage because out-of-pocket costs can be as little as $5/mo.
Contraindications are the same as those for the combined pill above: Substance use, cardiovascular disease, hyperthyroidism, glaucoma, MAOI use, and agitation. Again, take caution with patients who have hypertension, have congenital heart disease, or take SSRIs or insulin.
Side effects can include palpitations, tachycardia, dry mouth, headache, insomnia, and anxiety. The dose starts at 15 mg daily, and Fox advises following a similar follow-up as with the other medications, at which clinicians should assess BMI, the medication’s effect on eating, cardiovascular health, and side effects and have a discussion about off-label use. Off-label use refers to prescriptions lasting longer than 12 weeks, but it’s arguably safer than attention-deficit/hyperactivity disorder stimulants because of the lower addiction potential, Fox said.
What Else to Know
Because obesity is a chronic disease, treatment will be ongoing, Fox noted. A lot of people will ask when or where the “off-ramp” for these medications is, but many people will need these medications long term just as someone with other chronic diseases requires lifetime pharmacotherapy. The treatment intensity will vary based on disease severity and individual characteristics, Fox said.
For those feeling overwhelmed by the options, Fox advises clinicians to start by picking one medication to learn and then spending the time to read the FDA package insert in full. Get samples and then closely follow patients to learn that medication well before moving on to learn another. She also noted the opportunity for pediatricians to see a pediatric obesity medicine fellowship.
No external funding was used for the presentation. Fox is a site principal investigator for clinical trials sponsored by Novo Nordisk and Eli Lilly. Ivers had no disclosures.
A version of this article first appeared on Medscape.com.
ORLANDO, FLORIDA — The rationale for using obesity medications in pediatric patients is that it’s using “a biological intervention to treat a biologically based disease,” according to Claudia Fox, MD, MPH, an associate professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota, Minneapolis. At the annual meeting of the American Academy of Pediatrics (AAP), Fox provided
“This field is changing so rapidly that even over the course of the last 3 or 4 months, the verbiage around what we should be calling these interventions has changed,” Fox noted. Instead of “anti-obesity” medications, “most of us are now using the term obesity medications to highlight or to reduce chances of stigma and bias that can come along with this topic.”
Jessica Ivers, MD, a pediatrician at Swedish Pediatrics in Seattle, Washington, said she found the session very informative, particularly because she doesn’t think many pediatricians currently feel very comfortable prescribing obesity medications.
“It answered questions that any general pediatrician would have, and it’s kind of a new field that people are learning about,” Ivers said. “I think we just need more education. It’s just too new, and people haven’t had the education and the support from colleagues to [use the medications].”
Fox first reminded attendees of precisely what obesity is: A chronic, relapsing, multifactorial, neurobehavioral disease that involves the accumulation and/or distribution of excess body fat that results in impaired health. AAP clinical practice guidelines currently advise that youth aged 12 years or older who have obesity be offered weight loss pharmacotherapy as an adjunct to lifestyle treatment, taking into consideration the indications, risks, and benefits of each medication.
That doesn’t necessarily mean every child aged 12 years or older with a body mass index (BMI) of at least the 95th percentile should be prescribed one of these medications, Fox said. But pediatricians should start becoming familiar with the options and recognize that part of reducing the stigma of this disease is emphasizing that these medications are prescribed not for “weight loss” but to treat the disease of obesity, Fox said. The guidelines advise “early, intensive care” and focusing on the whole child, “using a family-centered and nonstigmatizing approach that acknowledges obesity’s biologic, social, and structural drivers.”
Offer the Full Spectrum of Care Early On
Early intervention means starting obesity treatment at diagnosis, without watchful waiting or the previously recommended staged approach. Instead of trying lifestyle therapy for 3-6 months, then considering the addition of medication, and then considering bariatric surgery, “we should be offering the full spectrum of obesity care as appropriate for that individual patient,” Fox said.
Some children with severe obesity may need the combination of lifestyle therapy and pharmacotherapy right up front, whereas another might be able to try lifestyle therapy alone for a while first. “What we know is that, for most interventions, whether it is lifestyle therapy, a medication, or bariatric surgery, early response typically predicts longer-term response,” Fox said. A study conducted by her group, for example, found that a 3% BMI reduction after 1 month with lifestyle therapy was very predictive of clinically meaningful BMI reduction at 1 year.
As with any medical treatment, physicians need to weigh the risks of the medication — short-term side effects and unknown long-term risks (or benefits) — against the risks of not treating. Because obesity is a progressive disease, “if we don’t treat it, most will develop comorbid conditions, or worsening of their already present comorbid conditions, and this does indeed lead to shortened life expectancy,” Fox said. Those who should be treated with medication are obviously those in whom the benefits outweigh the risks, Fox said, which depends on their age, their comorbidities, the severity of obesity, and the safety and efficacy of medication options.
“If I have a patient who has maybe class 2 obesity but no other comorbid conditions, I may be less inclined to start an obesity medication than a kid who has class 1 obesity and obstructive sleep apnea, for instance,” Fox said. “Some of the medications are very, very potent and effective. If you have a kid who maybe has less severe forms of obesity, perhaps they don’t need something that’s so potent.”
BMI trajectory is also a factor to consider. She said she may not be too concerned about a 16-year-old who has always been at the 95th percentile and is otherwise healthy, but the situation is different for a 16-year-old who used to be in the 25th percentile and has rapidly progressed to the 50th and then 75th percentiles in a trajectory heading straight up.
Another factor that may come into play is the patient and family preferences, though Fox noted that weight bias and stigma often interfere here. If obesity medications are brought up, the family may bring up the need for more exercise and better meal prep at home.
“They have this sense that they just need to try harder, that if they did that, the obesity would somehow get better on its own,” Fox said. “That’s an internalized bias that it’s somehow their fault, rather than realizing that this is indeed a biological disorder.”
Finally, clinicians may want to consider the child’s response to lifestyle therapy and whether they have already had bariatric surgery because these medications can be prescribed in people who did not have an adequate response to surgery.
Overview of the Medications
There are currently six obesity medications approved by the Food and Drug Administration (FDA) for use in youth: Phentermine, orlistat, liraglutide, phentermine/topiramate, semaglutide, and setmelanotide.
Of these, orlistat is rarely used now because it results in the least amount of change in BMI (about a 3% loss change in BMI), has a lot of gastrointestinal side effects, often is not covered by insurance, and is expensive out of pocket. Setmelanotide is indicated only in those aged 6 years or older who have obesity because of Bardet-Biedl syndrome or one of three other rare genetic conditions: a POMC, LEPR, or PCSK1 deficiency. Fox therefore focused on the other medications besides these two.
While nearly all the currently available obesity medications are only approved in those aged 12 years or older, Fox noted that studies are ongoing at younger ages, so some of these medications may receive approval in younger populations in the future. The only one currently available for a younger age is liraglutide, which is approved down to 6 years old in children with type 2 diabetes.
“Very young kids who have very severe forms of obesity need intervention, and unfortunately, at this point, we really don’t have much to offer them,” Fox said.
Fox highlighted six key factors to consider in selecting a medication for those aged 12 years or older, though one of these, in the US healthcare system, can tend to trump all the others. Those factors are mechanism of action, side effect profile, effects on other diagnoses, patient/family preferences, provider comfort, and finally — the potentially overruling one — insurance coverage and access.
“These days, insurance coverage and access are really the No. 1 driver when I’m seeing a patient,” Fox said. “The first thing I do is look at their insurance and then also look at what kind of updates our pharmacist has given us about which medication is currently in stock.”
Each medication has different properties that should be considered with the child’s health profile. For example, topiramate is a carbonic anhydrase inhibitor so likely shouldn’t be prescribed in a child who is taking any other carbonic anhydrase inhibitor. Fox said she probably wouldn’t prescribe phentermine in a child with severe anxiety because it might enhance the anxiety effect. But if a child has migraines, she may be more inclined to try phentermine/topiramate first because the topiramate may help with the migraines. Similarly, if a child has type 2 diabetes or prediabetes, she may lean toward one of the glucagon-like peptide 1 (GLP-1) agonist drugs.
Liraglutide and Semaglutide
Liraglutide and semaglutide are both GLP-1 receptor agonists administered subcutaneously to reduce appetite, increase satiety, slow gastric emptying, and reduce the food reward response in the brain. Liraglutide can result in up to 4.5%-5% change in BMI, and semaglutide, the most potent of all the medications, can result in up to a 17% change in BMI.
Liraglutide and semaglutide are both approved for patients aged 12 years or older who weigh at least 60 kg and have a BMI of at least the 95th percentile. Liraglutide is also approved for those aged 10 years or older with type 2 diabetes. Both are contraindicated in those with a family history of medullary thyroid cancer or multiple endocrine neoplasia II. The risks to watch for include pancreatitis and gallbladder disease. Also keep in mind if you have a patient with type 1 diabetes and insulin resistance; prescribing a GLP-1 agonist is appropriate, but their insulin needs will decrease, necessitating close monitoring of their blood glucose, Fox noted.
These GLP-1 medications can be considered for those who have insurance coverage for them, who have diabetes or prediabetes, who are comfortable with daily (liraglutide) or weekly (semaglutide) injections, who have food cravings, and who have poor satiety or satiation. Without insurance, these medications are very expensive.
The most common side effects include injection site reactions and nausea, vomiting, and diarrhea, though all these usually fade and can be minimized with small portions and slower eating if needed. Less common possible side effects can include abdominal pain, constipation, headache, dizziness, fatigue, and hypoglycemia. If patients develop severe belly pain that radiates to their back, they should be assessed for pancreatitis.
It’s also important to demonstrate for patients how to do the injections, Fox said. Liraglutide dosing begins at 0.6 mg daily for a week, followed by a week at 1.2 mg, a week at 1.8 mg, a week at 2.4 mg, and then 3 mg daily. Semaglutide dosing starts at 0.25 mg weekly for 4 weeks, then going up each subsequent month as needed to 0.5 mg, then 1 mg, then 1.7 mg, and finally 2.4 mg. Though there’s no standard follow-up schedule for these medications, Fox suggested considering monthly visits for the first 3 months and then every 2-3 months to assess heart rate and blood pressure, the injection site, adherence, side effects, and the effect on BMI and eating.
“Are they getting appetite suppression, but not too much appetite suppression?” Fox said. “Just like in eating disorder treatment, we want our patients to eat regularly spaced meals. If their appetite is so suppressed that they are hardly eating anything, that’s a problem.”
Fox also offered the following additional pearls about these medications:
- Though manufacturers have struggled to keep up with demand, the shortages of these medications are improving. However, beware the compounding pharmacies filling the gap because compounded medications are not FDA approved, and quality control issues are a concern.
- Prior authorizations are usually needed, and common reasons for denial to anticipate include lack of documentation on not having contraindications, the patient not following a low-calorie diet or engaging in physical activity, and the patient not having seen a registered dietitian.
- Patients should expect gastrointestinal side effects, but ondansetron can be prescribed to lessen the intensity.
Phentermine/Topiramate
Phentermine/topiramate extended-release is a once-daily oral tablet, with the phentermine acting to reduce appetite (by simulating the release of norepinephrine) and the topiramate reducing caloric intake and food reward response (by increasing gamma-aminobutyric acid activity). It’s approved for those aged 12 years or older with a BMI of at least the 95th percentile and should be considered in those with strong hunger, low energy, binge eating disorder, or migraines, as well as those who have insurance coverage for it. It can result in up to a 10% change in BMI.
Contraindications include pregnancy, substance use, cardiovascular disease (though it’s okay in patients with controlled hypertension), hyperthyroidism, glaucoma, and monoamine oxidase inhibitor (MAOI) use. Fox emphasized the teratogenic effects, so patients capable of pregnancy need to be on reliable birth control. The most common side effects include paresthesia, dizziness, dysgeusia, insomnia, and constipation.
A risk of topiramate is kidney stones, so patients should drink a lot of water, especially in hot weather, Fox said. Other risks can include metabolic acidosis, suicidality, poor cognitive function, high blood pressure, and renal impairment.
“If your patient is struggling academically, I might use this medication a bit more cautiously, particularly when the dose gets above 100 mg a day,” Fox said. “That’s when the cognitive effects tend to emerge more strongly.”
Patients with congenital heart disease should meet with their cardiologist before starting this medication, and although patients taking selective serotonin reuptake inhibitors (SSRIs) can take this, there is a potential increased risk for serotonin syndrome because phentermine has a little bit of serotonergic activity, she said.
Before prescribing, do an exam to ensure the patient doesn’t have a heart murmur, isn’t hypertensive, isn’t pregnant, has normal kidney function, and has bicarbonate in a reasonable range. Dosing begins with a daily 3.75/23-mg capsule for 2 weeks, followed by 2 weeks at 7.5 mg/46 mg. As with the GLP-1 drugs, Fox advises considering monthly follow-ups for the first 3 months and then visits every 2-3 months. Each visit should include the assessment of cardiovascular health, heart rate, blood pressure, side effects, pregnancy risk, and the medication’s effect on BMI and eating. If the patient is tolerating a dose of 7.5 mg/46 mg, it can be increased to 11.25 mg/69 mg for 2 weeks and then to 15 mg/92 mg. Bicarbonate and creatinine should be checked every 6-12 months; if bicarbonate < 18 mEq/L, the dose should be reduced and then bicarbonate should be checked again a month later.
Fox noted that this drug is expected to go off patent in late 2024 or in 2025, which will substantially reduce the cost. It’s also possible to prescribe phentermine and topiramate separately, which may reduce costs or help with insurance coverage and can allow for evening dosing of topiramate.
Phentermine
Phentermine alone is only approved for those older than 16 years who have a BMI of at least 30, or at least 27 with weight-related comorbidities, and it’s not approved for use longer than 12 weeks. It results in a BMI change of up to 5%. It should be considered in those with strong hunger and low energy and in those who don’t have adequate insurance coverage because out-of-pocket costs can be as little as $5/mo.
Contraindications are the same as those for the combined pill above: Substance use, cardiovascular disease, hyperthyroidism, glaucoma, MAOI use, and agitation. Again, take caution with patients who have hypertension, have congenital heart disease, or take SSRIs or insulin.
Side effects can include palpitations, tachycardia, dry mouth, headache, insomnia, and anxiety. The dose starts at 15 mg daily, and Fox advises following a similar follow-up as with the other medications, at which clinicians should assess BMI, the medication’s effect on eating, cardiovascular health, and side effects and have a discussion about off-label use. Off-label use refers to prescriptions lasting longer than 12 weeks, but it’s arguably safer than attention-deficit/hyperactivity disorder stimulants because of the lower addiction potential, Fox said.
What Else to Know
Because obesity is a chronic disease, treatment will be ongoing, Fox noted. A lot of people will ask when or where the “off-ramp” for these medications is, but many people will need these medications long term just as someone with other chronic diseases requires lifetime pharmacotherapy. The treatment intensity will vary based on disease severity and individual characteristics, Fox said.
For those feeling overwhelmed by the options, Fox advises clinicians to start by picking one medication to learn and then spending the time to read the FDA package insert in full. Get samples and then closely follow patients to learn that medication well before moving on to learn another. She also noted the opportunity for pediatricians to see a pediatric obesity medicine fellowship.
No external funding was used for the presentation. Fox is a site principal investigator for clinical trials sponsored by Novo Nordisk and Eli Lilly. Ivers had no disclosures.
A version of this article first appeared on Medscape.com.
FROM AAP 2024
Thyroid Cancer Overdiagnosis Continues Despite Cautions
according to a recently published global study.
The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.
Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.
Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.
Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.
“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”
Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.
This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.
Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.
“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
Persisting Problem
Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.
The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”
“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.
In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.
If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.
In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.
“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.
“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.
The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.
“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.
In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
New Thinking on Thyroid Cancer
There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.
“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”
The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.
Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.
“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.
Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.
“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.
Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.
“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”
Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.
“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”
This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a recently published global study.
The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.
Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.
Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.
Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.
“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”
Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.
This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.
Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.
“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
Persisting Problem
Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.
The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”
“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.
In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.
If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.
In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.
“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.
“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.
The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.
“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.
In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
New Thinking on Thyroid Cancer
There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.
“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”
The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.
Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.
“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.
Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.
“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.
Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.
“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”
Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.
“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”
This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a recently published global study.
The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.
Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.
Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.
Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.
“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”
Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.
This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.
Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.
“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
Persisting Problem
Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.
The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”
“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.
In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.
If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.
In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.
“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.
“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.
The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.
“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.
In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
New Thinking on Thyroid Cancer
There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.
“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”
The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.
Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.
“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.
Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.
“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.
Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.
“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”
Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.
“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”
This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
FROM THE LANCET DIABETES & ENDOCRINOLOGY
FIT Completion and Yield Similar in Younger and Older Adults
, a new study has found.
The study also found a similar low 3% rate of CRC detected at colonoscopy in both the younger and older adults.
“Our study suggests that adults ages 45-49 have a colorectal cancer risk that is similar to what we see in adults age 50,” senior author Jeffrey K. Lee, MD, MPH, gastroenterologist and research scientist at Kaiser Permanente Northern California Division of Research (DOR) in Oakland, California, said in a news release.
“The low number of cancers we found also provides support for initially offering younger adults a non-invasive test, like FIT, to determine which patients would benefit from a colonoscopy,” Lee noted.
Timely and Important Question
“This study addresses a timely and important clinical question, namely, is FIT an acceptable screening modality in patients aged 45-49,” Ziad F. Gellad, MD, MPH, AGAF, professor of medicine, Duke University Medical Center, Durham, North Carolina, who was not involved in the study, said in an interview.
“The finding that FIT completion and yield in younger patients is similar to those aged 50 and above is good news because it supports the use of this screening modality in the younger cohort,” said Gellad, section chief, gastroenterology, Durham VA Health Care System.
The study was published online in Annals of Internal Medicine.
In 2021, the US Preventive Services Task Force lowered the age to start CRC screening from 50 to 45 years, in response to studies showing an increased rate of CRC in adults aged 45-49 years.
The decision to start CRC screening at age 45 was made based on modeling studies, which are dependent on assumptions, co-first author Theodore R. Levin, MD, who is also a gastroenterologist and research scientist at Kaiser Permanente DOR, said in an interview.
“We thought it was important to collect real-world data on the experience of screening in this age group. We had no basis to know whether younger people would take up screening or if the yield of screening would be sufficiently high to warrant starting screening in this age group,” said Levin.
The researchers compared FIT screening completion and outcomes in 213,928 patients aged 45-49 years and 53,804 patients aged 50 years who received a FIT kit for the first time. The patients were from Kaiser Permanente Northern California, Washington, and Colorado.
Overall, FIT completion rates were slightly higher in the younger adults than in the 50-year-olds (38.9% vs 37.5%; adjusted risk ratio [aRR], 1.05), although the younger patients from Colorado were substantially less apt to complete a FIT (30.7% vs 40.2%; aRR, 0.77).
In the overall 45- to 49-year age group, 3.6% of adults had a positive FIT result, only slightly lower than the 4% positivity rate in the 50-year age group (aRR, 0.91).
About two thirds of adults in both groups who had a positive FIT result went on to have a colonoscopy within 3 months of receiving the test result.
Adenoma detection during colonoscopy was slightly lower in the younger than in the older group (58.8% vs 67.7%; aRR, 0.88). However, yields were similar for adenoma with advanced histology (13.2% vs 15.9%; aRR, 0.86), polyp with high-grade dysplasia (3.4% vs 5.1%; aRR, 0.68), sessile serrated lesion (10.3% vs 11.7%; aRR, 0.92), and CRC (2.8% vs 2.7%; aRR, 1.10).
FIT First Fits With Younger Adults’ Busy Lives
“Overall, people under 50 have lower incidence of cancer than people in their 50s, 60s, and 70s. However, if you do a test like FIT first, you can improve the yield of colonoscopy, which is a much more efficient strategy,” Levin said.
He noted that younger people are the least likely to be screened.
“They are busy with work and family responsibilities and may not realize that they are at risk for CRC. It is important to offer them a test that is easy to perform and does not require them to miss a day of work or arrange for a driver. They should be offered an option to screen with a stool-based test as an easy way to fit CRC screening into their busy lives,” Levin said.
Gellad said the study also highlights the limitations of FIT, “namely, that the low uptake and suboptimal colonoscopy follow-up of positive tests, also extend into the lower age group.”
Additionally, Gellad said he hopes other large systems will replicate this study to address the generalizability of these findings outside the Kaiser system.
The study was funded by the Kaiser Permanente Sydney R. Garfield Memorial Fund. Disclosures for study authors are available with the original article. Gellad consulted for Merck & Co. and Novo Nordisk and is a co-founder of Higgs Boson, Inc.
A version of this article appeared on Medscape.com.
, a new study has found.
The study also found a similar low 3% rate of CRC detected at colonoscopy in both the younger and older adults.
“Our study suggests that adults ages 45-49 have a colorectal cancer risk that is similar to what we see in adults age 50,” senior author Jeffrey K. Lee, MD, MPH, gastroenterologist and research scientist at Kaiser Permanente Northern California Division of Research (DOR) in Oakland, California, said in a news release.
“The low number of cancers we found also provides support for initially offering younger adults a non-invasive test, like FIT, to determine which patients would benefit from a colonoscopy,” Lee noted.
Timely and Important Question
“This study addresses a timely and important clinical question, namely, is FIT an acceptable screening modality in patients aged 45-49,” Ziad F. Gellad, MD, MPH, AGAF, professor of medicine, Duke University Medical Center, Durham, North Carolina, who was not involved in the study, said in an interview.
“The finding that FIT completion and yield in younger patients is similar to those aged 50 and above is good news because it supports the use of this screening modality in the younger cohort,” said Gellad, section chief, gastroenterology, Durham VA Health Care System.
The study was published online in Annals of Internal Medicine.
In 2021, the US Preventive Services Task Force lowered the age to start CRC screening from 50 to 45 years, in response to studies showing an increased rate of CRC in adults aged 45-49 years.
The decision to start CRC screening at age 45 was made based on modeling studies, which are dependent on assumptions, co-first author Theodore R. Levin, MD, who is also a gastroenterologist and research scientist at Kaiser Permanente DOR, said in an interview.
“We thought it was important to collect real-world data on the experience of screening in this age group. We had no basis to know whether younger people would take up screening or if the yield of screening would be sufficiently high to warrant starting screening in this age group,” said Levin.
The researchers compared FIT screening completion and outcomes in 213,928 patients aged 45-49 years and 53,804 patients aged 50 years who received a FIT kit for the first time. The patients were from Kaiser Permanente Northern California, Washington, and Colorado.
Overall, FIT completion rates were slightly higher in the younger adults than in the 50-year-olds (38.9% vs 37.5%; adjusted risk ratio [aRR], 1.05), although the younger patients from Colorado were substantially less apt to complete a FIT (30.7% vs 40.2%; aRR, 0.77).
In the overall 45- to 49-year age group, 3.6% of adults had a positive FIT result, only slightly lower than the 4% positivity rate in the 50-year age group (aRR, 0.91).
About two thirds of adults in both groups who had a positive FIT result went on to have a colonoscopy within 3 months of receiving the test result.
Adenoma detection during colonoscopy was slightly lower in the younger than in the older group (58.8% vs 67.7%; aRR, 0.88). However, yields were similar for adenoma with advanced histology (13.2% vs 15.9%; aRR, 0.86), polyp with high-grade dysplasia (3.4% vs 5.1%; aRR, 0.68), sessile serrated lesion (10.3% vs 11.7%; aRR, 0.92), and CRC (2.8% vs 2.7%; aRR, 1.10).
FIT First Fits With Younger Adults’ Busy Lives
“Overall, people under 50 have lower incidence of cancer than people in their 50s, 60s, and 70s. However, if you do a test like FIT first, you can improve the yield of colonoscopy, which is a much more efficient strategy,” Levin said.
He noted that younger people are the least likely to be screened.
“They are busy with work and family responsibilities and may not realize that they are at risk for CRC. It is important to offer them a test that is easy to perform and does not require them to miss a day of work or arrange for a driver. They should be offered an option to screen with a stool-based test as an easy way to fit CRC screening into their busy lives,” Levin said.
Gellad said the study also highlights the limitations of FIT, “namely, that the low uptake and suboptimal colonoscopy follow-up of positive tests, also extend into the lower age group.”
Additionally, Gellad said he hopes other large systems will replicate this study to address the generalizability of these findings outside the Kaiser system.
The study was funded by the Kaiser Permanente Sydney R. Garfield Memorial Fund. Disclosures for study authors are available with the original article. Gellad consulted for Merck & Co. and Novo Nordisk and is a co-founder of Higgs Boson, Inc.
A version of this article appeared on Medscape.com.
, a new study has found.
The study also found a similar low 3% rate of CRC detected at colonoscopy in both the younger and older adults.
“Our study suggests that adults ages 45-49 have a colorectal cancer risk that is similar to what we see in adults age 50,” senior author Jeffrey K. Lee, MD, MPH, gastroenterologist and research scientist at Kaiser Permanente Northern California Division of Research (DOR) in Oakland, California, said in a news release.
“The low number of cancers we found also provides support for initially offering younger adults a non-invasive test, like FIT, to determine which patients would benefit from a colonoscopy,” Lee noted.
Timely and Important Question
“This study addresses a timely and important clinical question, namely, is FIT an acceptable screening modality in patients aged 45-49,” Ziad F. Gellad, MD, MPH, AGAF, professor of medicine, Duke University Medical Center, Durham, North Carolina, who was not involved in the study, said in an interview.
“The finding that FIT completion and yield in younger patients is similar to those aged 50 and above is good news because it supports the use of this screening modality in the younger cohort,” said Gellad, section chief, gastroenterology, Durham VA Health Care System.
The study was published online in Annals of Internal Medicine.
In 2021, the US Preventive Services Task Force lowered the age to start CRC screening from 50 to 45 years, in response to studies showing an increased rate of CRC in adults aged 45-49 years.
The decision to start CRC screening at age 45 was made based on modeling studies, which are dependent on assumptions, co-first author Theodore R. Levin, MD, who is also a gastroenterologist and research scientist at Kaiser Permanente DOR, said in an interview.
“We thought it was important to collect real-world data on the experience of screening in this age group. We had no basis to know whether younger people would take up screening or if the yield of screening would be sufficiently high to warrant starting screening in this age group,” said Levin.
The researchers compared FIT screening completion and outcomes in 213,928 patients aged 45-49 years and 53,804 patients aged 50 years who received a FIT kit for the first time. The patients were from Kaiser Permanente Northern California, Washington, and Colorado.
Overall, FIT completion rates were slightly higher in the younger adults than in the 50-year-olds (38.9% vs 37.5%; adjusted risk ratio [aRR], 1.05), although the younger patients from Colorado were substantially less apt to complete a FIT (30.7% vs 40.2%; aRR, 0.77).
In the overall 45- to 49-year age group, 3.6% of adults had a positive FIT result, only slightly lower than the 4% positivity rate in the 50-year age group (aRR, 0.91).
About two thirds of adults in both groups who had a positive FIT result went on to have a colonoscopy within 3 months of receiving the test result.
Adenoma detection during colonoscopy was slightly lower in the younger than in the older group (58.8% vs 67.7%; aRR, 0.88). However, yields were similar for adenoma with advanced histology (13.2% vs 15.9%; aRR, 0.86), polyp with high-grade dysplasia (3.4% vs 5.1%; aRR, 0.68), sessile serrated lesion (10.3% vs 11.7%; aRR, 0.92), and CRC (2.8% vs 2.7%; aRR, 1.10).
FIT First Fits With Younger Adults’ Busy Lives
“Overall, people under 50 have lower incidence of cancer than people in their 50s, 60s, and 70s. However, if you do a test like FIT first, you can improve the yield of colonoscopy, which is a much more efficient strategy,” Levin said.
He noted that younger people are the least likely to be screened.
“They are busy with work and family responsibilities and may not realize that they are at risk for CRC. It is important to offer them a test that is easy to perform and does not require them to miss a day of work or arrange for a driver. They should be offered an option to screen with a stool-based test as an easy way to fit CRC screening into their busy lives,” Levin said.
Gellad said the study also highlights the limitations of FIT, “namely, that the low uptake and suboptimal colonoscopy follow-up of positive tests, also extend into the lower age group.”
Additionally, Gellad said he hopes other large systems will replicate this study to address the generalizability of these findings outside the Kaiser system.
The study was funded by the Kaiser Permanente Sydney R. Garfield Memorial Fund. Disclosures for study authors are available with the original article. Gellad consulted for Merck & Co. and Novo Nordisk and is a co-founder of Higgs Boson, Inc.
A version of this article appeared on Medscape.com.
Ultraprocessed Foods Associated With Relapse Risk in Crohn’s Disease
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM UEG 2024
Starting Mammograms at Age 40: Will Women Benefit?
Last April, the US Preventive Services Task Force (USPSTF) revised its breast cancer screening guidelines to recommend average-risk women start their screening mammograms at age 40, instead of age 50, and continue every other year until age 74.
The USPSTF’s recent recommendations align with those from major organizations, including the National Comprehensive Cancer Network and the American College of Radiology. The latest update comes from the American College of Obstetricians and Gynecologists (ACOG), which recommended a start age of 40 and continued screening either annually or every 2 years.
For USPSTF, the decision to recommend the earlier screening age, instead of keeping the choice an individualized one, was largely driven by the steady rise in breast cancer diagnoses among women in their 40s, alongside evidence that Black women are more likely to get breast cancer younger and die from the disease compared with White women.
But is this recommendation to screen earlier a change for the better?
Opinions vary.
USPSTF member John Wong, MD, chief of clinical decision making and a primary care physician at Tufts Medical Center in Boston, believes the new recommendation is the right move.
“It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women and there is even greater potential benefit for Black women, who are much more likely to die from breast cancer,” Wong told Medscape last year.
However, in a recent Viewpoint in JAMA Internal Medicine, experts from the University of California San Francisco expressed their reservations about shifting the recommended screening age a decade earlier.
The trio — Karla Kerlikowske, MD, Laura Esserman, MD, and Jeffrey Tice, MD — called the new recommendations “surprising” given the lack of new randomized control trial data to support the change as well as data that show breast cancer deaths have been decreasing among women, including younger women.
More specifically, breast cancer deaths for women under 50 have decreased from 5.9 to 3.9 per 100,000 individuals between 2000 and 2020 — a decline that can likely be attributed to better treatments rather than increased screening effectiveness, the Viewpoint authors said.
However, moving the screening age earlier would not markedly improve survival for most women, the authors argued. According to USPSTF modeling, starting mammograms at age 40 instead of 50 could avert only 1.3 additional breast cancer deaths per 1000 women screened biennially and 1.8 additional breast cancer deaths among Black women.
Starting screening at 40, however, does come with an array of potential harms. These include 65 more benign biopsies per 1000 women screened, 1 in 2 women with a false-positive mammography result (503 per 1000), and 1 in 500 women with an over-diagnosed breast cancer, meaning the cancer would not have become clinically evident in their lifetime.
The use of digital breast tomosynthesis can slightly reduce the number of false-positives and benign biopsies compared to older mammography techniques, but these small improvements did not sway the overall pro-con assessment for the Viewpoint authors.
“False-positive results require additional imaging and are associated with anxiety for patients,” the authors noted. “Women who have benign biopsies may experience the potential adverse effects of biopsies, such as bleeding, infection, and scarring unnecessarily; and over-diagnosis may lead to unnecessary treatment.”
Kenneth Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency in Pennsylvania, agreed that starting mammograms at age 40 is not a change for the better.
Lin and colleagues conducted an analysis based on data from the USPSTF’s 2016 breast cancer screening report that similarly found 1 additional breast cancer death prevented per 1000 women screened starting at 40 vs 50, at a cost of 576 more false-positive results, 67 more benign breast biopsies, and 2 women diagnosed and treated unnecessarily.
Overall, “there is no compelling evidence to change our clinical approach to breast cancer screening for women in their 40s: individual decision-making based on patient preferences and values,” Lin wrote in a recent Medscape commentary.
But several experts not involved in the USPSTF recommendations agree with the change.
The updated recommendation to begin mammograms at age 40 for women at average risk “aligns with accumulating data suggesting that earlier and more frequent screening can save more lives, and is widely seen as a positive step,” said Lisa Abramson, MD, a radiologist specializing in breast imaging with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York City.
Melissa Fana, MD, a breast surgical oncologist at NYU Langone Health, agreed that the revised recommendation is justified and “will undoubtedly save lives.”
“The recent change in the screening recommendation was meant to be inclusive, and provide women, particularly women aged 40 to 49 the opportunity to screen with mammography,” Fana said.
One major argument in favor of earlier screening is that it will help address racial inequities in breast cancer diagnoses, treatment, and deaths. Despite a 5% lower incidence of breast cancer, Black women are more likely to be diagnosed with distant-stage cancer or more aggressive breast cancer subtypes, such as triple-negative, compared with White women, and are more likely to die from breast cancer.
“We hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” said Cherie C. Hill, MD, FACOG, an ob.gyn. at Emory Healthcare in Atlanta, who coauthored the recent ACOG recommendations.
The Viewpoint authors Kerlikowske, Esserman and Tice agreed that Black women may benefit more from earlier screening. However, earlier screening does not address the underlying disparities in treatment and follow-up care for Black women, and it is unclear whether screening alone will help improve breast cancer mortality rates for Black women, the authors noted.
There is one place where experts seem to align: the importance of educating patients about their personal risk.
The Viewpoint authors favor a risk-based approach to help women decide whether to start screening before age 50.
“Engaging women in informed decision-making based on their invasive and advanced breast cancer risk would be a patient-centered approach toward tailored screening, informing when to consider starting screening and how often to screen,” the experts wrote.
For a woman to truly make an educated decision on whether she would like to screen or wait after age 40, she would at least need to know what her specific lifetime risk of developing breast cancer is, not the average risk is for American women in general, Fana told this news organization.
“Risk assessment calculators are widely available and include factors such as family history and reproductive history, and this information can evolve over time and affect lifetime risk,” Fana noted. But “some women just do not get this information.”
Abramson explained that ob.gyns. and primary care physicians will likely play a larger role in the early assessment of breast cancer risk, including discussions about genetic testing and personal risk factors starting as early as age 25.
“For clinicians, the emphasis may be on educating patients about their individual risk, ensuring timely mammograms, and referring higher-risk individuals for further testing or consultations with specialists,” Abramson added.
Esserman reported being a Blue Cross Medical Advisory Panel member, an uncompensated board member of Quantum Leap Healthcare Collaborative, which funds the I-SPY trial through the University of California, San Francisco, and having an investigator-initiated trial for high-risk ductal carcinoma in situ (DCIS) funded through UCSF by Moderna for a DCIS phase 1 study. Tice and Kerlikowske reported receiving grants from the National Cancer Institute outside the submitted work. Abramson and Fana have no relevant disclosures.
A version of this article appeared on Medscape.com.
Last April, the US Preventive Services Task Force (USPSTF) revised its breast cancer screening guidelines to recommend average-risk women start their screening mammograms at age 40, instead of age 50, and continue every other year until age 74.
The USPSTF’s recent recommendations align with those from major organizations, including the National Comprehensive Cancer Network and the American College of Radiology. The latest update comes from the American College of Obstetricians and Gynecologists (ACOG), which recommended a start age of 40 and continued screening either annually or every 2 years.
For USPSTF, the decision to recommend the earlier screening age, instead of keeping the choice an individualized one, was largely driven by the steady rise in breast cancer diagnoses among women in their 40s, alongside evidence that Black women are more likely to get breast cancer younger and die from the disease compared with White women.
But is this recommendation to screen earlier a change for the better?
Opinions vary.
USPSTF member John Wong, MD, chief of clinical decision making and a primary care physician at Tufts Medical Center in Boston, believes the new recommendation is the right move.
“It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women and there is even greater potential benefit for Black women, who are much more likely to die from breast cancer,” Wong told Medscape last year.
However, in a recent Viewpoint in JAMA Internal Medicine, experts from the University of California San Francisco expressed their reservations about shifting the recommended screening age a decade earlier.
The trio — Karla Kerlikowske, MD, Laura Esserman, MD, and Jeffrey Tice, MD — called the new recommendations “surprising” given the lack of new randomized control trial data to support the change as well as data that show breast cancer deaths have been decreasing among women, including younger women.
More specifically, breast cancer deaths for women under 50 have decreased from 5.9 to 3.9 per 100,000 individuals between 2000 and 2020 — a decline that can likely be attributed to better treatments rather than increased screening effectiveness, the Viewpoint authors said.
However, moving the screening age earlier would not markedly improve survival for most women, the authors argued. According to USPSTF modeling, starting mammograms at age 40 instead of 50 could avert only 1.3 additional breast cancer deaths per 1000 women screened biennially and 1.8 additional breast cancer deaths among Black women.
Starting screening at 40, however, does come with an array of potential harms. These include 65 more benign biopsies per 1000 women screened, 1 in 2 women with a false-positive mammography result (503 per 1000), and 1 in 500 women with an over-diagnosed breast cancer, meaning the cancer would not have become clinically evident in their lifetime.
The use of digital breast tomosynthesis can slightly reduce the number of false-positives and benign biopsies compared to older mammography techniques, but these small improvements did not sway the overall pro-con assessment for the Viewpoint authors.
“False-positive results require additional imaging and are associated with anxiety for patients,” the authors noted. “Women who have benign biopsies may experience the potential adverse effects of biopsies, such as bleeding, infection, and scarring unnecessarily; and over-diagnosis may lead to unnecessary treatment.”
Kenneth Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency in Pennsylvania, agreed that starting mammograms at age 40 is not a change for the better.
Lin and colleagues conducted an analysis based on data from the USPSTF’s 2016 breast cancer screening report that similarly found 1 additional breast cancer death prevented per 1000 women screened starting at 40 vs 50, at a cost of 576 more false-positive results, 67 more benign breast biopsies, and 2 women diagnosed and treated unnecessarily.
Overall, “there is no compelling evidence to change our clinical approach to breast cancer screening for women in their 40s: individual decision-making based on patient preferences and values,” Lin wrote in a recent Medscape commentary.
But several experts not involved in the USPSTF recommendations agree with the change.
The updated recommendation to begin mammograms at age 40 for women at average risk “aligns with accumulating data suggesting that earlier and more frequent screening can save more lives, and is widely seen as a positive step,” said Lisa Abramson, MD, a radiologist specializing in breast imaging with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York City.
Melissa Fana, MD, a breast surgical oncologist at NYU Langone Health, agreed that the revised recommendation is justified and “will undoubtedly save lives.”
“The recent change in the screening recommendation was meant to be inclusive, and provide women, particularly women aged 40 to 49 the opportunity to screen with mammography,” Fana said.
One major argument in favor of earlier screening is that it will help address racial inequities in breast cancer diagnoses, treatment, and deaths. Despite a 5% lower incidence of breast cancer, Black women are more likely to be diagnosed with distant-stage cancer or more aggressive breast cancer subtypes, such as triple-negative, compared with White women, and are more likely to die from breast cancer.
“We hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” said Cherie C. Hill, MD, FACOG, an ob.gyn. at Emory Healthcare in Atlanta, who coauthored the recent ACOG recommendations.
The Viewpoint authors Kerlikowske, Esserman and Tice agreed that Black women may benefit more from earlier screening. However, earlier screening does not address the underlying disparities in treatment and follow-up care for Black women, and it is unclear whether screening alone will help improve breast cancer mortality rates for Black women, the authors noted.
There is one place where experts seem to align: the importance of educating patients about their personal risk.
The Viewpoint authors favor a risk-based approach to help women decide whether to start screening before age 50.
“Engaging women in informed decision-making based on their invasive and advanced breast cancer risk would be a patient-centered approach toward tailored screening, informing when to consider starting screening and how often to screen,” the experts wrote.
For a woman to truly make an educated decision on whether she would like to screen or wait after age 40, she would at least need to know what her specific lifetime risk of developing breast cancer is, not the average risk is for American women in general, Fana told this news organization.
“Risk assessment calculators are widely available and include factors such as family history and reproductive history, and this information can evolve over time and affect lifetime risk,” Fana noted. But “some women just do not get this information.”
Abramson explained that ob.gyns. and primary care physicians will likely play a larger role in the early assessment of breast cancer risk, including discussions about genetic testing and personal risk factors starting as early as age 25.
“For clinicians, the emphasis may be on educating patients about their individual risk, ensuring timely mammograms, and referring higher-risk individuals for further testing or consultations with specialists,” Abramson added.
Esserman reported being a Blue Cross Medical Advisory Panel member, an uncompensated board member of Quantum Leap Healthcare Collaborative, which funds the I-SPY trial through the University of California, San Francisco, and having an investigator-initiated trial for high-risk ductal carcinoma in situ (DCIS) funded through UCSF by Moderna for a DCIS phase 1 study. Tice and Kerlikowske reported receiving grants from the National Cancer Institute outside the submitted work. Abramson and Fana have no relevant disclosures.
A version of this article appeared on Medscape.com.
Last April, the US Preventive Services Task Force (USPSTF) revised its breast cancer screening guidelines to recommend average-risk women start their screening mammograms at age 40, instead of age 50, and continue every other year until age 74.
The USPSTF’s recent recommendations align with those from major organizations, including the National Comprehensive Cancer Network and the American College of Radiology. The latest update comes from the American College of Obstetricians and Gynecologists (ACOG), which recommended a start age of 40 and continued screening either annually or every 2 years.
For USPSTF, the decision to recommend the earlier screening age, instead of keeping the choice an individualized one, was largely driven by the steady rise in breast cancer diagnoses among women in their 40s, alongside evidence that Black women are more likely to get breast cancer younger and die from the disease compared with White women.
But is this recommendation to screen earlier a change for the better?
Opinions vary.
USPSTF member John Wong, MD, chief of clinical decision making and a primary care physician at Tufts Medical Center in Boston, believes the new recommendation is the right move.
“It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women and there is even greater potential benefit for Black women, who are much more likely to die from breast cancer,” Wong told Medscape last year.
However, in a recent Viewpoint in JAMA Internal Medicine, experts from the University of California San Francisco expressed their reservations about shifting the recommended screening age a decade earlier.
The trio — Karla Kerlikowske, MD, Laura Esserman, MD, and Jeffrey Tice, MD — called the new recommendations “surprising” given the lack of new randomized control trial data to support the change as well as data that show breast cancer deaths have been decreasing among women, including younger women.
More specifically, breast cancer deaths for women under 50 have decreased from 5.9 to 3.9 per 100,000 individuals between 2000 and 2020 — a decline that can likely be attributed to better treatments rather than increased screening effectiveness, the Viewpoint authors said.
However, moving the screening age earlier would not markedly improve survival for most women, the authors argued. According to USPSTF modeling, starting mammograms at age 40 instead of 50 could avert only 1.3 additional breast cancer deaths per 1000 women screened biennially and 1.8 additional breast cancer deaths among Black women.
Starting screening at 40, however, does come with an array of potential harms. These include 65 more benign biopsies per 1000 women screened, 1 in 2 women with a false-positive mammography result (503 per 1000), and 1 in 500 women with an over-diagnosed breast cancer, meaning the cancer would not have become clinically evident in their lifetime.
The use of digital breast tomosynthesis can slightly reduce the number of false-positives and benign biopsies compared to older mammography techniques, but these small improvements did not sway the overall pro-con assessment for the Viewpoint authors.
“False-positive results require additional imaging and are associated with anxiety for patients,” the authors noted. “Women who have benign biopsies may experience the potential adverse effects of biopsies, such as bleeding, infection, and scarring unnecessarily; and over-diagnosis may lead to unnecessary treatment.”
Kenneth Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency in Pennsylvania, agreed that starting mammograms at age 40 is not a change for the better.
Lin and colleagues conducted an analysis based on data from the USPSTF’s 2016 breast cancer screening report that similarly found 1 additional breast cancer death prevented per 1000 women screened starting at 40 vs 50, at a cost of 576 more false-positive results, 67 more benign breast biopsies, and 2 women diagnosed and treated unnecessarily.
Overall, “there is no compelling evidence to change our clinical approach to breast cancer screening for women in their 40s: individual decision-making based on patient preferences and values,” Lin wrote in a recent Medscape commentary.
But several experts not involved in the USPSTF recommendations agree with the change.
The updated recommendation to begin mammograms at age 40 for women at average risk “aligns with accumulating data suggesting that earlier and more frequent screening can save more lives, and is widely seen as a positive step,” said Lisa Abramson, MD, a radiologist specializing in breast imaging with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York City.
Melissa Fana, MD, a breast surgical oncologist at NYU Langone Health, agreed that the revised recommendation is justified and “will undoubtedly save lives.”
“The recent change in the screening recommendation was meant to be inclusive, and provide women, particularly women aged 40 to 49 the opportunity to screen with mammography,” Fana said.
One major argument in favor of earlier screening is that it will help address racial inequities in breast cancer diagnoses, treatment, and deaths. Despite a 5% lower incidence of breast cancer, Black women are more likely to be diagnosed with distant-stage cancer or more aggressive breast cancer subtypes, such as triple-negative, compared with White women, and are more likely to die from breast cancer.
“We hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” said Cherie C. Hill, MD, FACOG, an ob.gyn. at Emory Healthcare in Atlanta, who coauthored the recent ACOG recommendations.
The Viewpoint authors Kerlikowske, Esserman and Tice agreed that Black women may benefit more from earlier screening. However, earlier screening does not address the underlying disparities in treatment and follow-up care for Black women, and it is unclear whether screening alone will help improve breast cancer mortality rates for Black women, the authors noted.
There is one place where experts seem to align: the importance of educating patients about their personal risk.
The Viewpoint authors favor a risk-based approach to help women decide whether to start screening before age 50.
“Engaging women in informed decision-making based on their invasive and advanced breast cancer risk would be a patient-centered approach toward tailored screening, informing when to consider starting screening and how often to screen,” the experts wrote.
For a woman to truly make an educated decision on whether she would like to screen or wait after age 40, she would at least need to know what her specific lifetime risk of developing breast cancer is, not the average risk is for American women in general, Fana told this news organization.
“Risk assessment calculators are widely available and include factors such as family history and reproductive history, and this information can evolve over time and affect lifetime risk,” Fana noted. But “some women just do not get this information.”
Abramson explained that ob.gyns. and primary care physicians will likely play a larger role in the early assessment of breast cancer risk, including discussions about genetic testing and personal risk factors starting as early as age 25.
“For clinicians, the emphasis may be on educating patients about their individual risk, ensuring timely mammograms, and referring higher-risk individuals for further testing or consultations with specialists,” Abramson added.
Esserman reported being a Blue Cross Medical Advisory Panel member, an uncompensated board member of Quantum Leap Healthcare Collaborative, which funds the I-SPY trial through the University of California, San Francisco, and having an investigator-initiated trial for high-risk ductal carcinoma in situ (DCIS) funded through UCSF by Moderna for a DCIS phase 1 study. Tice and Kerlikowske reported receiving grants from the National Cancer Institute outside the submitted work. Abramson and Fana have no relevant disclosures.
A version of this article appeared on Medscape.com.