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Fighting for fresh air: RSV’s connection to environmental pollution
Diffuse Lung Disease and Lung Transplant Network
Occupational and Environmental Health Section
Poor air quality has numerous health hazards for patients with chronic lung disease. Now mounting evidence from pediatric studies suggests a concerning link between air pollution and viral infections, specifically respiratory syncytial virus (RSV).
Multiple studies have shown increased incidence and severity of disease in children with exposure to air pollutants such as particulate matter and nitrogen dioxide.1,2,3 Researchers speculate that these pollutants potentiate viral entry to airway epithelium, increase viral load, and dysregulate the immune response.4 Air pollution, increasingly worsened by climate change, is also associated with acute respiratory infections in adults, though adult research remains sparse.5
The adoption of viral testing during the pandemic has revealed a previously under-recognized prevalence of RSV in adults.
RSV accounts for an estimated 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths annually among elderly adults. This newfound awareness coincides with the exciting development of a new RSV vaccine that has shown around 85% efficacy at preventing symptomatic RSV infection in the first year, and new data suggest benefits persisting even into the second year after vaccination.6 With an estimated 60 million adults at high risk for RSV in the US, RSV prevention has become an increasingly important aspect of respiratory care.
While more research is needed to definitively quantify the link between air pollution and RSV in adults, the existing data offer valuable insights for all pulmonologists. These findings suggest a benefit in counseling patients with chronic lung conditions on taking steps to mitigate exposure to air pollutants, either through avoidance of outdoor activities or mask-wearing when air quality levels exceed healthy ranges, as well as promoting RSV vaccination for patients who are at risk.7
References
1. Milani GP, Cafora M, Favero C, et al. PM2.5, PM10 and bronchiolitis severity: a cohort study. Pediatr Allergy Immunol. 2022;33(10). https://doi.org/10.1111/pai.13853
2. Wrotek A, Badyda A, Czechowski PO, Owczarek T, Dąbrowiecki P, Jackowska T. Air pollutants’ concentrations are associated with increased number of RSV hospitalizations in Polish children. J Clin Med. 2021;10(15):3224. https://doi.org/10.3390/jcm10153224
3. Horne BD, Joy EA, Hofmann MG, et al. Short-term elevation of fine particulate matter air pollution and acute lower respiratory infection. Am J Respir Crit Care Med. 2018;198(6):759-766. https://doi.org/10.1164/rccm.201709-1883oc
4. Wrotek A, Jackowska T. Molecular mechanisms of RSV and air pollution interaction: a scoping review. Int J Mol Sci. 2022;23(20):12704. https://doi.org/10.3390/ijms232012704
5. Kirwa K, Eckert CM, Vedal S, Hajat A, Kaufman JD. Ambient air pollution and risk of respiratory infection among adults: evidence from the multiethnic study of atherosclerosis (MESA). BMJ Open Respir Res. 2021;8(1). https://doi.org/10.1136/bmjresp-2020-000866
6. Melgar M, Britton A, Roper LE, et al. Use of respiratory syncytial virus vaccines in older adults: recommendations of the Advisory Committee on Immunization Practices — United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):793-801. http://dx.doi.org/10.15585/mmwr.mm7229a4
7. Kodros JK, O’Dell K, Samet JM, L’Orange C, Pierce JR, Volckens J. Quantifying the health benefits of face masks and respirators to mitigate exposure to severe air pollution. GeoHealth. 2021;5(9). https://doi.org/10.1029/2021gh000482
Diffuse Lung Disease and Lung Transplant Network
Occupational and Environmental Health Section
Poor air quality has numerous health hazards for patients with chronic lung disease. Now mounting evidence from pediatric studies suggests a concerning link between air pollution and viral infections, specifically respiratory syncytial virus (RSV).
Multiple studies have shown increased incidence and severity of disease in children with exposure to air pollutants such as particulate matter and nitrogen dioxide.1,2,3 Researchers speculate that these pollutants potentiate viral entry to airway epithelium, increase viral load, and dysregulate the immune response.4 Air pollution, increasingly worsened by climate change, is also associated with acute respiratory infections in adults, though adult research remains sparse.5
The adoption of viral testing during the pandemic has revealed a previously under-recognized prevalence of RSV in adults.
RSV accounts for an estimated 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths annually among elderly adults. This newfound awareness coincides with the exciting development of a new RSV vaccine that has shown around 85% efficacy at preventing symptomatic RSV infection in the first year, and new data suggest benefits persisting even into the second year after vaccination.6 With an estimated 60 million adults at high risk for RSV in the US, RSV prevention has become an increasingly important aspect of respiratory care.
While more research is needed to definitively quantify the link between air pollution and RSV in adults, the existing data offer valuable insights for all pulmonologists. These findings suggest a benefit in counseling patients with chronic lung conditions on taking steps to mitigate exposure to air pollutants, either through avoidance of outdoor activities or mask-wearing when air quality levels exceed healthy ranges, as well as promoting RSV vaccination for patients who are at risk.7
References
1. Milani GP, Cafora M, Favero C, et al. PM2.5, PM10 and bronchiolitis severity: a cohort study. Pediatr Allergy Immunol. 2022;33(10). https://doi.org/10.1111/pai.13853
2. Wrotek A, Badyda A, Czechowski PO, Owczarek T, Dąbrowiecki P, Jackowska T. Air pollutants’ concentrations are associated with increased number of RSV hospitalizations in Polish children. J Clin Med. 2021;10(15):3224. https://doi.org/10.3390/jcm10153224
3. Horne BD, Joy EA, Hofmann MG, et al. Short-term elevation of fine particulate matter air pollution and acute lower respiratory infection. Am J Respir Crit Care Med. 2018;198(6):759-766. https://doi.org/10.1164/rccm.201709-1883oc
4. Wrotek A, Jackowska T. Molecular mechanisms of RSV and air pollution interaction: a scoping review. Int J Mol Sci. 2022;23(20):12704. https://doi.org/10.3390/ijms232012704
5. Kirwa K, Eckert CM, Vedal S, Hajat A, Kaufman JD. Ambient air pollution and risk of respiratory infection among adults: evidence from the multiethnic study of atherosclerosis (MESA). BMJ Open Respir Res. 2021;8(1). https://doi.org/10.1136/bmjresp-2020-000866
6. Melgar M, Britton A, Roper LE, et al. Use of respiratory syncytial virus vaccines in older adults: recommendations of the Advisory Committee on Immunization Practices — United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):793-801. http://dx.doi.org/10.15585/mmwr.mm7229a4
7. Kodros JK, O’Dell K, Samet JM, L’Orange C, Pierce JR, Volckens J. Quantifying the health benefits of face masks and respirators to mitigate exposure to severe air pollution. GeoHealth. 2021;5(9). https://doi.org/10.1029/2021gh000482
Diffuse Lung Disease and Lung Transplant Network
Occupational and Environmental Health Section
Poor air quality has numerous health hazards for patients with chronic lung disease. Now mounting evidence from pediatric studies suggests a concerning link between air pollution and viral infections, specifically respiratory syncytial virus (RSV).
Multiple studies have shown increased incidence and severity of disease in children with exposure to air pollutants such as particulate matter and nitrogen dioxide.1,2,3 Researchers speculate that these pollutants potentiate viral entry to airway epithelium, increase viral load, and dysregulate the immune response.4 Air pollution, increasingly worsened by climate change, is also associated with acute respiratory infections in adults, though adult research remains sparse.5
The adoption of viral testing during the pandemic has revealed a previously under-recognized prevalence of RSV in adults.
RSV accounts for an estimated 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths annually among elderly adults. This newfound awareness coincides with the exciting development of a new RSV vaccine that has shown around 85% efficacy at preventing symptomatic RSV infection in the first year, and new data suggest benefits persisting even into the second year after vaccination.6 With an estimated 60 million adults at high risk for RSV in the US, RSV prevention has become an increasingly important aspect of respiratory care.
While more research is needed to definitively quantify the link between air pollution and RSV in adults, the existing data offer valuable insights for all pulmonologists. These findings suggest a benefit in counseling patients with chronic lung conditions on taking steps to mitigate exposure to air pollutants, either through avoidance of outdoor activities or mask-wearing when air quality levels exceed healthy ranges, as well as promoting RSV vaccination for patients who are at risk.7
References
1. Milani GP, Cafora M, Favero C, et al. PM2.5, PM10 and bronchiolitis severity: a cohort study. Pediatr Allergy Immunol. 2022;33(10). https://doi.org/10.1111/pai.13853
2. Wrotek A, Badyda A, Czechowski PO, Owczarek T, Dąbrowiecki P, Jackowska T. Air pollutants’ concentrations are associated with increased number of RSV hospitalizations in Polish children. J Clin Med. 2021;10(15):3224. https://doi.org/10.3390/jcm10153224
3. Horne BD, Joy EA, Hofmann MG, et al. Short-term elevation of fine particulate matter air pollution and acute lower respiratory infection. Am J Respir Crit Care Med. 2018;198(6):759-766. https://doi.org/10.1164/rccm.201709-1883oc
4. Wrotek A, Jackowska T. Molecular mechanisms of RSV and air pollution interaction: a scoping review. Int J Mol Sci. 2022;23(20):12704. https://doi.org/10.3390/ijms232012704
5. Kirwa K, Eckert CM, Vedal S, Hajat A, Kaufman JD. Ambient air pollution and risk of respiratory infection among adults: evidence from the multiethnic study of atherosclerosis (MESA). BMJ Open Respir Res. 2021;8(1). https://doi.org/10.1136/bmjresp-2020-000866
6. Melgar M, Britton A, Roper LE, et al. Use of respiratory syncytial virus vaccines in older adults: recommendations of the Advisory Committee on Immunization Practices — United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):793-801. http://dx.doi.org/10.15585/mmwr.mm7229a4
7. Kodros JK, O’Dell K, Samet JM, L’Orange C, Pierce JR, Volckens J. Quantifying the health benefits of face masks and respirators to mitigate exposure to severe air pollution. GeoHealth. 2021;5(9). https://doi.org/10.1029/2021gh000482
A word of caution on e-cigarettes: Retracted paper
Editor’s note: On March 29, 2024, the authors of the study, “Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial,” published in JAMA Internal Medicine, issued a formal retraction of their article. The CHEST Physician® Editorial Board apologizes for any confusion this may have caused.
An article in the April issue of the CHEST Physician publication headlined, “E-cigarettes beat nicotine gum for smoking cessation,” was based on an article in JAMA Internal Medicine by Liu Z and colleagues which was subsequently retracted by the author due to coding errors and discrepancies in calculations that cast doubt on the accuracy and reliability of the reported findings.
One should be cautious in evaluating claims of the benefits of electronic cigarettes (e-cigarettes). e-Cigarettes are a highly addictive and largely unregulated product. The fine print in previous clinical trials of e-cigarettes shows greater rates of stopping nicotine products—including e-cigarettes—in the groups assigned to recommendation for nicotine replacement therapy. e-Cigarettes have substantial acute and chronic harms.
Although much of the research to date is from animal models, there is a growing body of evidence in humans that validates the findings from the animal models. In laboratory animal models, e-cigarettes impair airway defenses, contribute to epithelial dysfunction, lead to apoptosis of airway cells, cause emphysematous changes, and lead to increased cancer rates.
Adverse effects on cardiovascular health have also been demonstrated. There is evidence of genotoxicity from e-cigarette exposure, with increased rates of DNA damage and decreased rates of DNA repair. Carcinogenic substances are present in e-cigarettes, and we may not see the carcinogenic effects in humans for several years or even decades. Commonly used flavoring chemicals have substantial pulmonary toxicity. There is evidence that the dual use of e-cigarettes and combustible tobacco can be more harmful than the use of combustible tobacco alone, as the person who smokes is now exposed to additional toxins unique to the e-cigarette.
E-cigarettes can cause severe acute lung disease; 14% of the severe e-cigarette or vaping product use-associated lung injury (EVALI) cases reported use of only nicotine-containing e-cigarette products. There are reports of people who used e-cigarettes who required lung transplant due to complications of their e-cigarette use.
The tobacco industry has a long history of “harm reduction” products that were anything but—from filter cigarettes (the “advanced” Kent Micronite filter contained asbestos) to the so-called low tar and nicotine cigarettes (which were no less harmful). There is a long history of physicians endorsing these products as “must be better.” The growing evidence that e-cigarettes carry distinct health risks of their own should prompt us to consider a broader picture beyond just comparing them with traditional cigarettes to assess their impact on health.
Physicians treating tobacco dependence should recommend US Food and Drug Administration-approved medications for pharmacotherapy. These have a robust evidence base documenting that they help people who smoke to break free of nicotine addiction. The goal of tobacco dependence treatment should be stopping ALL harmful tobacco/nicotine products—including e-cigarettes—not simply changing from one harmful product to another.
References
Liu Z. Notice of retraction: Lin HX et al. Efficacy of electronic cigarettes vs varenicline and nicotine chewing gum as an aid to stop smoking: a randomized clinical trial. JAMA Intern Med. 2024;184(3):291-299. JAMA Intern Med. Preprint. Posted online March 29, 2024. PMID: 38551593. doi: 10.1001/jamainternmed.2024.1125
Farber HJ, Conrado Pacheco Gallego M, Galiatsatos P, Folan P, Lamphere T, Pakhale S. Harms of electronic cigarettes: what the healthcare provider needs to know. Ann Am Thorac Soc. 2021;18(4):567-572. PMID: 33284731. doi: 10.1513/AnnalsATS.202009-1113CME
Proctor RN. Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition. University of California Press; 2011.
Auer R, Schoeni A, Humair JP, et al. Electronic nicotine-delivery systems for smoking cessation. N Engl J Med. 2024;390(7):601-610. PMID: 38354139. doi: 10.1056/NEJMoa2308815
Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019;380(7):629-637. Preprint. Posted online January 30, 2019. PMID: 30699054. doi: 10.1056/NEJMoa1808779
Editor’s note: On March 29, 2024, the authors of the study, “Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial,” published in JAMA Internal Medicine, issued a formal retraction of their article. The CHEST Physician® Editorial Board apologizes for any confusion this may have caused.
An article in the April issue of the CHEST Physician publication headlined, “E-cigarettes beat nicotine gum for smoking cessation,” was based on an article in JAMA Internal Medicine by Liu Z and colleagues which was subsequently retracted by the author due to coding errors and discrepancies in calculations that cast doubt on the accuracy and reliability of the reported findings.
One should be cautious in evaluating claims of the benefits of electronic cigarettes (e-cigarettes). e-Cigarettes are a highly addictive and largely unregulated product. The fine print in previous clinical trials of e-cigarettes shows greater rates of stopping nicotine products—including e-cigarettes—in the groups assigned to recommendation for nicotine replacement therapy. e-Cigarettes have substantial acute and chronic harms.
Although much of the research to date is from animal models, there is a growing body of evidence in humans that validates the findings from the animal models. In laboratory animal models, e-cigarettes impair airway defenses, contribute to epithelial dysfunction, lead to apoptosis of airway cells, cause emphysematous changes, and lead to increased cancer rates.
Adverse effects on cardiovascular health have also been demonstrated. There is evidence of genotoxicity from e-cigarette exposure, with increased rates of DNA damage and decreased rates of DNA repair. Carcinogenic substances are present in e-cigarettes, and we may not see the carcinogenic effects in humans for several years or even decades. Commonly used flavoring chemicals have substantial pulmonary toxicity. There is evidence that the dual use of e-cigarettes and combustible tobacco can be more harmful than the use of combustible tobacco alone, as the person who smokes is now exposed to additional toxins unique to the e-cigarette.
E-cigarettes can cause severe acute lung disease; 14% of the severe e-cigarette or vaping product use-associated lung injury (EVALI) cases reported use of only nicotine-containing e-cigarette products. There are reports of people who used e-cigarettes who required lung transplant due to complications of their e-cigarette use.
The tobacco industry has a long history of “harm reduction” products that were anything but—from filter cigarettes (the “advanced” Kent Micronite filter contained asbestos) to the so-called low tar and nicotine cigarettes (which were no less harmful). There is a long history of physicians endorsing these products as “must be better.” The growing evidence that e-cigarettes carry distinct health risks of their own should prompt us to consider a broader picture beyond just comparing them with traditional cigarettes to assess their impact on health.
Physicians treating tobacco dependence should recommend US Food and Drug Administration-approved medications for pharmacotherapy. These have a robust evidence base documenting that they help people who smoke to break free of nicotine addiction. The goal of tobacco dependence treatment should be stopping ALL harmful tobacco/nicotine products—including e-cigarettes—not simply changing from one harmful product to another.
References
Liu Z. Notice of retraction: Lin HX et al. Efficacy of electronic cigarettes vs varenicline and nicotine chewing gum as an aid to stop smoking: a randomized clinical trial. JAMA Intern Med. 2024;184(3):291-299. JAMA Intern Med. Preprint. Posted online March 29, 2024. PMID: 38551593. doi: 10.1001/jamainternmed.2024.1125
Farber HJ, Conrado Pacheco Gallego M, Galiatsatos P, Folan P, Lamphere T, Pakhale S. Harms of electronic cigarettes: what the healthcare provider needs to know. Ann Am Thorac Soc. 2021;18(4):567-572. PMID: 33284731. doi: 10.1513/AnnalsATS.202009-1113CME
Proctor RN. Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition. University of California Press; 2011.
Auer R, Schoeni A, Humair JP, et al. Electronic nicotine-delivery systems for smoking cessation. N Engl J Med. 2024;390(7):601-610. PMID: 38354139. doi: 10.1056/NEJMoa2308815
Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019;380(7):629-637. Preprint. Posted online January 30, 2019. PMID: 30699054. doi: 10.1056/NEJMoa1808779
Editor’s note: On March 29, 2024, the authors of the study, “Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial,” published in JAMA Internal Medicine, issued a formal retraction of their article. The CHEST Physician® Editorial Board apologizes for any confusion this may have caused.
An article in the April issue of the CHEST Physician publication headlined, “E-cigarettes beat nicotine gum for smoking cessation,” was based on an article in JAMA Internal Medicine by Liu Z and colleagues which was subsequently retracted by the author due to coding errors and discrepancies in calculations that cast doubt on the accuracy and reliability of the reported findings.
One should be cautious in evaluating claims of the benefits of electronic cigarettes (e-cigarettes). e-Cigarettes are a highly addictive and largely unregulated product. The fine print in previous clinical trials of e-cigarettes shows greater rates of stopping nicotine products—including e-cigarettes—in the groups assigned to recommendation for nicotine replacement therapy. e-Cigarettes have substantial acute and chronic harms.
Although much of the research to date is from animal models, there is a growing body of evidence in humans that validates the findings from the animal models. In laboratory animal models, e-cigarettes impair airway defenses, contribute to epithelial dysfunction, lead to apoptosis of airway cells, cause emphysematous changes, and lead to increased cancer rates.
Adverse effects on cardiovascular health have also been demonstrated. There is evidence of genotoxicity from e-cigarette exposure, with increased rates of DNA damage and decreased rates of DNA repair. Carcinogenic substances are present in e-cigarettes, and we may not see the carcinogenic effects in humans for several years or even decades. Commonly used flavoring chemicals have substantial pulmonary toxicity. There is evidence that the dual use of e-cigarettes and combustible tobacco can be more harmful than the use of combustible tobacco alone, as the person who smokes is now exposed to additional toxins unique to the e-cigarette.
E-cigarettes can cause severe acute lung disease; 14% of the severe e-cigarette or vaping product use-associated lung injury (EVALI) cases reported use of only nicotine-containing e-cigarette products. There are reports of people who used e-cigarettes who required lung transplant due to complications of their e-cigarette use.
The tobacco industry has a long history of “harm reduction” products that were anything but—from filter cigarettes (the “advanced” Kent Micronite filter contained asbestos) to the so-called low tar and nicotine cigarettes (which were no less harmful). There is a long history of physicians endorsing these products as “must be better.” The growing evidence that e-cigarettes carry distinct health risks of their own should prompt us to consider a broader picture beyond just comparing them with traditional cigarettes to assess their impact on health.
Physicians treating tobacco dependence should recommend US Food and Drug Administration-approved medications for pharmacotherapy. These have a robust evidence base documenting that they help people who smoke to break free of nicotine addiction. The goal of tobacco dependence treatment should be stopping ALL harmful tobacco/nicotine products—including e-cigarettes—not simply changing from one harmful product to another.
References
Liu Z. Notice of retraction: Lin HX et al. Efficacy of electronic cigarettes vs varenicline and nicotine chewing gum as an aid to stop smoking: a randomized clinical trial. JAMA Intern Med. 2024;184(3):291-299. JAMA Intern Med. Preprint. Posted online March 29, 2024. PMID: 38551593. doi: 10.1001/jamainternmed.2024.1125
Farber HJ, Conrado Pacheco Gallego M, Galiatsatos P, Folan P, Lamphere T, Pakhale S. Harms of electronic cigarettes: what the healthcare provider needs to know. Ann Am Thorac Soc. 2021;18(4):567-572. PMID: 33284731. doi: 10.1513/AnnalsATS.202009-1113CME
Proctor RN. Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition. University of California Press; 2011.
Auer R, Schoeni A, Humair JP, et al. Electronic nicotine-delivery systems for smoking cessation. N Engl J Med. 2024;390(7):601-610. PMID: 38354139. doi: 10.1056/NEJMoa2308815
Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019;380(7):629-637. Preprint. Posted online January 30, 2019. PMID: 30699054. doi: 10.1056/NEJMoa1808779
Fellow to use diversity scholar mentorship to strengthen care in pediatric-to-adult transitions
During residency training at the Rush University Medical Center in Internal Medicine and Pediatrics, Esha Kapania, MD, quickly became interested in the pulmonary pathologies that span the life of a patient, beginning in childhood and lasting into adulthood.
Now in her first year of fellowship at the University of Louisville and as the recipient of the 2024 Medical Educator Scholar Diversity Fellowship from CHEST and the Association of Pulmonary and Critical Care Medicine Program Directors (APCCMPD), Dr. Kapania will utilize the support of the program to explore this space.
“Recent advancements in pediatric pulmonary medicine have prolonged the expected lifespan of many previously fatal diagnoses, and I have realized that, despite these innovations, there remains very little communication between the adult and pediatric subspecialists,” Dr. Kapania said. “There is minimal education on congenital pulmonary pathology in adult medicine and, perhaps equally as important, negligible instruction on the cultural and social changes that patients experience when they transition from pediatric to adult providers.”
In residency, Dr. Kapania witnessed the success of cystic fibrosis (CF) clinics and hopes to leverage that experience to advance transitional care across disease states. Using the guidelines set to transition patients with CF from pediatric to adult care as a model, Dr. Kapania will focus her time on creating a streamlined process for patients living with severe asthma and patients with neuromuscular diseases who are chronically vented.
“Patients who are chronically vented tend not to have a lot of resources dedicated to them and are a resource- and time-heavy population,” Dr. Kapania said. “Because there is no defined process to transition these patients, we tend to see pediatric providers hold on to these patients for a lot longer than they do with [patients with CF]. A set of evidence-based practices would go a long way in this space.”
Through the APCCMPD and CHEST Medical Educator Scholar Diversity Fellowship, Dr. Kapania will work closely with the program’s selected mentor, Başak Çoruh, MD, FCCP, who is an Associate Professor of Pulmonary, Critical Care, and Sleep Medicine and Director of the Pulmonary and Critical Care Medicine fellowship program at the University of Washington.
“I’m looking forward to working with Dr. Çoruh for career guidance and for support of my area of interest within [pulmonary and critical care medicine],” Dr. Kapania said. “She is an established physician who has a lot of insight to share, and this is a great opportunity to make the best of my fellowship.”
This is the first year for the APCCMPD and CHEST Medical Educator Scholar Diversity Fellowship. To learn more about the scholarship, visit the CHEST website.
During residency training at the Rush University Medical Center in Internal Medicine and Pediatrics, Esha Kapania, MD, quickly became interested in the pulmonary pathologies that span the life of a patient, beginning in childhood and lasting into adulthood.
Now in her first year of fellowship at the University of Louisville and as the recipient of the 2024 Medical Educator Scholar Diversity Fellowship from CHEST and the Association of Pulmonary and Critical Care Medicine Program Directors (APCCMPD), Dr. Kapania will utilize the support of the program to explore this space.
“Recent advancements in pediatric pulmonary medicine have prolonged the expected lifespan of many previously fatal diagnoses, and I have realized that, despite these innovations, there remains very little communication between the adult and pediatric subspecialists,” Dr. Kapania said. “There is minimal education on congenital pulmonary pathology in adult medicine and, perhaps equally as important, negligible instruction on the cultural and social changes that patients experience when they transition from pediatric to adult providers.”
In residency, Dr. Kapania witnessed the success of cystic fibrosis (CF) clinics and hopes to leverage that experience to advance transitional care across disease states. Using the guidelines set to transition patients with CF from pediatric to adult care as a model, Dr. Kapania will focus her time on creating a streamlined process for patients living with severe asthma and patients with neuromuscular diseases who are chronically vented.
“Patients who are chronically vented tend not to have a lot of resources dedicated to them and are a resource- and time-heavy population,” Dr. Kapania said. “Because there is no defined process to transition these patients, we tend to see pediatric providers hold on to these patients for a lot longer than they do with [patients with CF]. A set of evidence-based practices would go a long way in this space.”
Through the APCCMPD and CHEST Medical Educator Scholar Diversity Fellowship, Dr. Kapania will work closely with the program’s selected mentor, Başak Çoruh, MD, FCCP, who is an Associate Professor of Pulmonary, Critical Care, and Sleep Medicine and Director of the Pulmonary and Critical Care Medicine fellowship program at the University of Washington.
“I’m looking forward to working with Dr. Çoruh for career guidance and for support of my area of interest within [pulmonary and critical care medicine],” Dr. Kapania said. “She is an established physician who has a lot of insight to share, and this is a great opportunity to make the best of my fellowship.”
This is the first year for the APCCMPD and CHEST Medical Educator Scholar Diversity Fellowship. To learn more about the scholarship, visit the CHEST website.
During residency training at the Rush University Medical Center in Internal Medicine and Pediatrics, Esha Kapania, MD, quickly became interested in the pulmonary pathologies that span the life of a patient, beginning in childhood and lasting into adulthood.
Now in her first year of fellowship at the University of Louisville and as the recipient of the 2024 Medical Educator Scholar Diversity Fellowship from CHEST and the Association of Pulmonary and Critical Care Medicine Program Directors (APCCMPD), Dr. Kapania will utilize the support of the program to explore this space.
“Recent advancements in pediatric pulmonary medicine have prolonged the expected lifespan of many previously fatal diagnoses, and I have realized that, despite these innovations, there remains very little communication between the adult and pediatric subspecialists,” Dr. Kapania said. “There is minimal education on congenital pulmonary pathology in adult medicine and, perhaps equally as important, negligible instruction on the cultural and social changes that patients experience when they transition from pediatric to adult providers.”
In residency, Dr. Kapania witnessed the success of cystic fibrosis (CF) clinics and hopes to leverage that experience to advance transitional care across disease states. Using the guidelines set to transition patients with CF from pediatric to adult care as a model, Dr. Kapania will focus her time on creating a streamlined process for patients living with severe asthma and patients with neuromuscular diseases who are chronically vented.
“Patients who are chronically vented tend not to have a lot of resources dedicated to them and are a resource- and time-heavy population,” Dr. Kapania said. “Because there is no defined process to transition these patients, we tend to see pediatric providers hold on to these patients for a lot longer than they do with [patients with CF]. A set of evidence-based practices would go a long way in this space.”
Through the APCCMPD and CHEST Medical Educator Scholar Diversity Fellowship, Dr. Kapania will work closely with the program’s selected mentor, Başak Çoruh, MD, FCCP, who is an Associate Professor of Pulmonary, Critical Care, and Sleep Medicine and Director of the Pulmonary and Critical Care Medicine fellowship program at the University of Washington.
“I’m looking forward to working with Dr. Çoruh for career guidance and for support of my area of interest within [pulmonary and critical care medicine],” Dr. Kapania said. “She is an established physician who has a lot of insight to share, and this is a great opportunity to make the best of my fellowship.”
This is the first year for the APCCMPD and CHEST Medical Educator Scholar Diversity Fellowship. To learn more about the scholarship, visit the CHEST website.
Transesophageal ultrasound: The future of ultrasound in the ICU
Thoracic Oncology and Chest Procedures Network
Ultrasound and Chest Imaging Section
Historically, transesophageal ultrasound (TEE) has been regarded as a diagnostic and management tool for structural heart disease in relatively stable patients. However, TEE is more commonly being utilized by intensivists as a first-line tool in the diagnostics and management of patients in the ICU.
TEE, with its unobstructed superior cardiac views, facilitates rapid diagnosis in undifferentiated shock and guides appropriate resuscitation efforts. Studies have shown that TEE alters management strategies in 40% of cases, following transthoracic echocardiography with an extremely low complication rate of 2% to 3% (primarily in the form of self-limited gastrointestinal bleeding).1,2,3,4
TEE also provides ultrasonographic evaluation of the lungs through transesophageal lung ultrasound (TELUS). TELUS allows for visualization of all six traditional lung zones utilized in traditional lung ultrasound.5 Patients with severe acute respiratory distress syndrome may greatly benefit from TEE utilization. TEE enables early detection of right ventricular dysfunction, aids in fluid management, and assesses the severity of lung consolidation, thereby facilitating prompt utilization of prone positioning or adjustments in positive end-expiratory pressure.
Cardiac arrest is another unique opportunity for TEE utilization by providing real-time cardiac visualization during active cardiopulmonary resuscitation. This facilitates optimal chest compression positioning, early recognition of arrhythmia, timely identification of reversible cause, and procedural guidance for ECMO-assisted CPR.6 TEE is an invaluable tool for the modern-day intensivist, providing rapid and accurate assessments, and therefore holds the potential to become standard of care in the ICU.
References
1. Prager R, Bowdridge J, Pratte M, Cheng J, McInnes MD, Arntfield R. Indications, clinical impact, and complications of critical care transesophageal echocardiography: a scoping review. J Intensive Care Med. 2023;38(3):245-272. Preprint. Posted online July 19, 2022. PMID: 35854414; PMCID: PMC9806486. doi: 10.1177/08850666221115348
2. Hüttemann E, Schelenz C, Kara F, Chatzinikolaou K, Reinhart K. The use and safety of transoesophageal echocardiography in the general ICU – a minireview. Acta Anaesthesiol Scand. 2004;48(7):827-36. PMID: 15242426. doi: 10.1111/j.0001-5172.2004.00423.x
3. Mayo PH, Narasimhan M, Koenig S. Critical care transesophageal echocardiography. Chest. 2015;148(5):1323-1332. PMID: 26204465. doi: 10.1378/chest.15-0260
4. Prager R, Ainsworth C, Arntfield R. Critical care transesophageal echocardiography for the resuscitation of shock: an important diagnostic skill for the modern intensivist. Chest. 2023;163(2):268-269. PMID: 36759112. doi: 10.1016/j.chest.2022.09.001
5. Cavayas YA, Girard M, Desjardins G, Denault AY. Transesophageal lung ultrasonography: a novel technique for investigating hypoxemia. Can J Anaesth. 2016;63(11):1266-76. Preprint. Posted online July 29, 2016. PMID: 27473720. doi: 10.1007/s12630-016-0702-2
6. Teran F, Prats MI, Nelson BP, et al. Focused transesophageal echocardiography during cardiac arrest resuscitation: JACC review wopic of the Week. J Am Coll Cardiol. 2020;76(6):745-754. PMID: 32762909. doi: 10.1016/j.jacc.2020.05.074
Thoracic Oncology and Chest Procedures Network
Ultrasound and Chest Imaging Section
Historically, transesophageal ultrasound (TEE) has been regarded as a diagnostic and management tool for structural heart disease in relatively stable patients. However, TEE is more commonly being utilized by intensivists as a first-line tool in the diagnostics and management of patients in the ICU.
TEE, with its unobstructed superior cardiac views, facilitates rapid diagnosis in undifferentiated shock and guides appropriate resuscitation efforts. Studies have shown that TEE alters management strategies in 40% of cases, following transthoracic echocardiography with an extremely low complication rate of 2% to 3% (primarily in the form of self-limited gastrointestinal bleeding).1,2,3,4
TEE also provides ultrasonographic evaluation of the lungs through transesophageal lung ultrasound (TELUS). TELUS allows for visualization of all six traditional lung zones utilized in traditional lung ultrasound.5 Patients with severe acute respiratory distress syndrome may greatly benefit from TEE utilization. TEE enables early detection of right ventricular dysfunction, aids in fluid management, and assesses the severity of lung consolidation, thereby facilitating prompt utilization of prone positioning or adjustments in positive end-expiratory pressure.
Cardiac arrest is another unique opportunity for TEE utilization by providing real-time cardiac visualization during active cardiopulmonary resuscitation. This facilitates optimal chest compression positioning, early recognition of arrhythmia, timely identification of reversible cause, and procedural guidance for ECMO-assisted CPR.6 TEE is an invaluable tool for the modern-day intensivist, providing rapid and accurate assessments, and therefore holds the potential to become standard of care in the ICU.
References
1. Prager R, Bowdridge J, Pratte M, Cheng J, McInnes MD, Arntfield R. Indications, clinical impact, and complications of critical care transesophageal echocardiography: a scoping review. J Intensive Care Med. 2023;38(3):245-272. Preprint. Posted online July 19, 2022. PMID: 35854414; PMCID: PMC9806486. doi: 10.1177/08850666221115348
2. Hüttemann E, Schelenz C, Kara F, Chatzinikolaou K, Reinhart K. The use and safety of transoesophageal echocardiography in the general ICU – a minireview. Acta Anaesthesiol Scand. 2004;48(7):827-36. PMID: 15242426. doi: 10.1111/j.0001-5172.2004.00423.x
3. Mayo PH, Narasimhan M, Koenig S. Critical care transesophageal echocardiography. Chest. 2015;148(5):1323-1332. PMID: 26204465. doi: 10.1378/chest.15-0260
4. Prager R, Ainsworth C, Arntfield R. Critical care transesophageal echocardiography for the resuscitation of shock: an important diagnostic skill for the modern intensivist. Chest. 2023;163(2):268-269. PMID: 36759112. doi: 10.1016/j.chest.2022.09.001
5. Cavayas YA, Girard M, Desjardins G, Denault AY. Transesophageal lung ultrasonography: a novel technique for investigating hypoxemia. Can J Anaesth. 2016;63(11):1266-76. Preprint. Posted online July 29, 2016. PMID: 27473720. doi: 10.1007/s12630-016-0702-2
6. Teran F, Prats MI, Nelson BP, et al. Focused transesophageal echocardiography during cardiac arrest resuscitation: JACC review wopic of the Week. J Am Coll Cardiol. 2020;76(6):745-754. PMID: 32762909. doi: 10.1016/j.jacc.2020.05.074
Thoracic Oncology and Chest Procedures Network
Ultrasound and Chest Imaging Section
Historically, transesophageal ultrasound (TEE) has been regarded as a diagnostic and management tool for structural heart disease in relatively stable patients. However, TEE is more commonly being utilized by intensivists as a first-line tool in the diagnostics and management of patients in the ICU.
TEE, with its unobstructed superior cardiac views, facilitates rapid diagnosis in undifferentiated shock and guides appropriate resuscitation efforts. Studies have shown that TEE alters management strategies in 40% of cases, following transthoracic echocardiography with an extremely low complication rate of 2% to 3% (primarily in the form of self-limited gastrointestinal bleeding).1,2,3,4
TEE also provides ultrasonographic evaluation of the lungs through transesophageal lung ultrasound (TELUS). TELUS allows for visualization of all six traditional lung zones utilized in traditional lung ultrasound.5 Patients with severe acute respiratory distress syndrome may greatly benefit from TEE utilization. TEE enables early detection of right ventricular dysfunction, aids in fluid management, and assesses the severity of lung consolidation, thereby facilitating prompt utilization of prone positioning or adjustments in positive end-expiratory pressure.
Cardiac arrest is another unique opportunity for TEE utilization by providing real-time cardiac visualization during active cardiopulmonary resuscitation. This facilitates optimal chest compression positioning, early recognition of arrhythmia, timely identification of reversible cause, and procedural guidance for ECMO-assisted CPR.6 TEE is an invaluable tool for the modern-day intensivist, providing rapid and accurate assessments, and therefore holds the potential to become standard of care in the ICU.
References
1. Prager R, Bowdridge J, Pratte M, Cheng J, McInnes MD, Arntfield R. Indications, clinical impact, and complications of critical care transesophageal echocardiography: a scoping review. J Intensive Care Med. 2023;38(3):245-272. Preprint. Posted online July 19, 2022. PMID: 35854414; PMCID: PMC9806486. doi: 10.1177/08850666221115348
2. Hüttemann E, Schelenz C, Kara F, Chatzinikolaou K, Reinhart K. The use and safety of transoesophageal echocardiography in the general ICU – a minireview. Acta Anaesthesiol Scand. 2004;48(7):827-36. PMID: 15242426. doi: 10.1111/j.0001-5172.2004.00423.x
3. Mayo PH, Narasimhan M, Koenig S. Critical care transesophageal echocardiography. Chest. 2015;148(5):1323-1332. PMID: 26204465. doi: 10.1378/chest.15-0260
4. Prager R, Ainsworth C, Arntfield R. Critical care transesophageal echocardiography for the resuscitation of shock: an important diagnostic skill for the modern intensivist. Chest. 2023;163(2):268-269. PMID: 36759112. doi: 10.1016/j.chest.2022.09.001
5. Cavayas YA, Girard M, Desjardins G, Denault AY. Transesophageal lung ultrasonography: a novel technique for investigating hypoxemia. Can J Anaesth. 2016;63(11):1266-76. Preprint. Posted online July 29, 2016. PMID: 27473720. doi: 10.1007/s12630-016-0702-2
6. Teran F, Prats MI, Nelson BP, et al. Focused transesophageal echocardiography during cardiac arrest resuscitation: JACC review wopic of the Week. J Am Coll Cardiol. 2020;76(6):745-754. PMID: 32762909. doi: 10.1016/j.jacc.2020.05.074
The pendulum swings in favor of corticosteroids
Critical Care Network
Sepsis/Shock Section
The pendulum swings in favor of corticosteroids and endorses the colloquialism among intensivists that no patient shall die without steroids, especially as it relates to sepsis and septic shock.
In 2018, we saw divergence among randomized controlled trials in the use of glucocorticoids for adults with septic shock such that hydrocortisone without the use of fludrocortisone showed no 90-day mortality benefit; however, hydrocortisone with fludrocortisone showed a 90-day mortality benefit.1,2 The Surviving Sepsis Guidelines in 2021 favored using low-dose corticosteroids in those with persistent vasopressor requirements in whom other core interventions had been instituted.
In 2023, a patient-level meta-analysis of low-dose hydrocortisone in adults with septic shock included seven trials and failed to demonstrate a mortality benefit by relative risk in those who received hydrocortisone compared with placebo. Separately, a network meta-analysis with hydrocortisone plus enteral fludrocortisone was associated with a 90-day all-cause mortality. Of the secondary outcomes, these results offered a possible association of hydrocortisone with a decreased risk of ICU mortality and with increased vasopressor-free days.3
The 2024 Society of Critical Care Medicine recently shared an update of focused guidelines on the use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. These included a conditional recommendation to administer corticosteroids for patients with septic shock but recommended against high-dose/short-duration administration of corticosteroids in these patients. These guidelines were supported by data from 46 randomized controlled trials, which showed that corticosteroid use may reduce hospital/long-term mortality and ICU/short-term mortality, as well as result in higher rates of shock reversal and reduced organ dysfunction.
With the results of these meta-analyses and randomized controlled trials, clinicians should consider low-dose corticosteroids paired with fludrocortisone as a tool in treating patients with septic shock given that the short- and long-term benefits may exceed any risks.
References
1. Venkatesh B, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378:797-808.
2. Annane D, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018;378:809-818.
3. Pirracchio R, et al. Patient-level meta-analysis of low-dose hydrocortisone in adults with septic shock. NEJM Evid. 2023;2(6).
Critical Care Network
Sepsis/Shock Section
The pendulum swings in favor of corticosteroids and endorses the colloquialism among intensivists that no patient shall die without steroids, especially as it relates to sepsis and septic shock.
In 2018, we saw divergence among randomized controlled trials in the use of glucocorticoids for adults with septic shock such that hydrocortisone without the use of fludrocortisone showed no 90-day mortality benefit; however, hydrocortisone with fludrocortisone showed a 90-day mortality benefit.1,2 The Surviving Sepsis Guidelines in 2021 favored using low-dose corticosteroids in those with persistent vasopressor requirements in whom other core interventions had been instituted.
In 2023, a patient-level meta-analysis of low-dose hydrocortisone in adults with septic shock included seven trials and failed to demonstrate a mortality benefit by relative risk in those who received hydrocortisone compared with placebo. Separately, a network meta-analysis with hydrocortisone plus enteral fludrocortisone was associated with a 90-day all-cause mortality. Of the secondary outcomes, these results offered a possible association of hydrocortisone with a decreased risk of ICU mortality and with increased vasopressor-free days.3
The 2024 Society of Critical Care Medicine recently shared an update of focused guidelines on the use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. These included a conditional recommendation to administer corticosteroids for patients with septic shock but recommended against high-dose/short-duration administration of corticosteroids in these patients. These guidelines were supported by data from 46 randomized controlled trials, which showed that corticosteroid use may reduce hospital/long-term mortality and ICU/short-term mortality, as well as result in higher rates of shock reversal and reduced organ dysfunction.
With the results of these meta-analyses and randomized controlled trials, clinicians should consider low-dose corticosteroids paired with fludrocortisone as a tool in treating patients with septic shock given that the short- and long-term benefits may exceed any risks.
References
1. Venkatesh B, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378:797-808.
2. Annane D, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018;378:809-818.
3. Pirracchio R, et al. Patient-level meta-analysis of low-dose hydrocortisone in adults with septic shock. NEJM Evid. 2023;2(6).
Critical Care Network
Sepsis/Shock Section
The pendulum swings in favor of corticosteroids and endorses the colloquialism among intensivists that no patient shall die without steroids, especially as it relates to sepsis and septic shock.
In 2018, we saw divergence among randomized controlled trials in the use of glucocorticoids for adults with septic shock such that hydrocortisone without the use of fludrocortisone showed no 90-day mortality benefit; however, hydrocortisone with fludrocortisone showed a 90-day mortality benefit.1,2 The Surviving Sepsis Guidelines in 2021 favored using low-dose corticosteroids in those with persistent vasopressor requirements in whom other core interventions had been instituted.
In 2023, a patient-level meta-analysis of low-dose hydrocortisone in adults with septic shock included seven trials and failed to demonstrate a mortality benefit by relative risk in those who received hydrocortisone compared with placebo. Separately, a network meta-analysis with hydrocortisone plus enteral fludrocortisone was associated with a 90-day all-cause mortality. Of the secondary outcomes, these results offered a possible association of hydrocortisone with a decreased risk of ICU mortality and with increased vasopressor-free days.3
The 2024 Society of Critical Care Medicine recently shared an update of focused guidelines on the use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. These included a conditional recommendation to administer corticosteroids for patients with septic shock but recommended against high-dose/short-duration administration of corticosteroids in these patients. These guidelines were supported by data from 46 randomized controlled trials, which showed that corticosteroid use may reduce hospital/long-term mortality and ICU/short-term mortality, as well as result in higher rates of shock reversal and reduced organ dysfunction.
With the results of these meta-analyses and randomized controlled trials, clinicians should consider low-dose corticosteroids paired with fludrocortisone as a tool in treating patients with septic shock given that the short- and long-term benefits may exceed any risks.
References
1. Venkatesh B, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378:797-808.
2. Annane D, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018;378:809-818.
3. Pirracchio R, et al. Patient-level meta-analysis of low-dose hydrocortisone in adults with septic shock. NEJM Evid. 2023;2(6).
Is it time to embrace a multinight sleep study?
Sleep Medicine Network
Respiratory-Related Sleep Disorders Section
Since the 1960s, sleep researchers have been intrigued by the first-night effect (FNE) in polysomnography (PSG) studies. A meta-analysis by Ding and colleagues revealed FNE’s impact on sleep metrics, like total sleep time and REM sleep, without affecting the apnea-hypopnea index, highlighting PSG’s limitations in simulating natural sleep patterns.1
Lechat and colleagues conducted a study using a home-based sleep analyzer on more than 67,000 individuals, averaging 170 nights each.2 This study found that single-night studies could lead to a 20% misdiagnosis rate in OSA, attributed to overlooking real sleep factors such as body posture, environmental effects, alcohol, and medication. Despite this, the wider use of multinight studies for accurate diagnosis is limited by insurance coverage issues.3
The last decade has seen substantial advances in health technology, particularly in consumer wearables capable of detecting various medical conditions. Devices employing techniques like actigraphy and accelerometry have reached a level of performance comparable with US Food and Drug Administration-approved clinical tools. However, these technologies are still in development for the diagnosis and classification of sleep-disordered breathing.
Tech companies are actively innovating sleep sensing technologies, smartwatches, bed sensors, wireless EEG, radiofrequency, and ultrasound sensors. With significant investments in this sector, these technologies could be ready for widespread use in the next 5 to 10 years. Health care professionals should consider data from sleep-tracking wearables when there are inconsistencies between a patient’s sleep study results and symptoms. The insights from these devices could provide crucial diagnostic information, enhancing the accuracy of sleep disorder diagnoses.
References
1. Ding L, Chen B, Dai Y, Li Y. A meta-analysis of the first-night effect in healthy individuals for the full age spectrum. Sleep Med. 2022;89:159-165. Preprint. Posted online December 17, 2021. PMID: 34998093. doi: 10.1016/j.sleep.2021.12.007
2. Lechat B, Naik G, Reynolds A, et al. Multinight prevalence, variability, and diagnostic misclassification of obstructive sleep apnea. Am J Respir Crit Care Med. 2022;205(5):563-569. PMID: 34904935; PMCID: PMC8906484. doi: 10.1164/rccm.202107-1761OC
3. Abreu A, Punjabi NM. How many nights are really needed to diagnose obstructive sleep apnea? Am J Respir Crit Care Med. 2022;206(1):125-126. PMID: 35476613; PMCID: PMC9954337. doi: 10.1164/rccm.202112-2837LE
Sleep Medicine Network
Respiratory-Related Sleep Disorders Section
Since the 1960s, sleep researchers have been intrigued by the first-night effect (FNE) in polysomnography (PSG) studies. A meta-analysis by Ding and colleagues revealed FNE’s impact on sleep metrics, like total sleep time and REM sleep, without affecting the apnea-hypopnea index, highlighting PSG’s limitations in simulating natural sleep patterns.1
Lechat and colleagues conducted a study using a home-based sleep analyzer on more than 67,000 individuals, averaging 170 nights each.2 This study found that single-night studies could lead to a 20% misdiagnosis rate in OSA, attributed to overlooking real sleep factors such as body posture, environmental effects, alcohol, and medication. Despite this, the wider use of multinight studies for accurate diagnosis is limited by insurance coverage issues.3
The last decade has seen substantial advances in health technology, particularly in consumer wearables capable of detecting various medical conditions. Devices employing techniques like actigraphy and accelerometry have reached a level of performance comparable with US Food and Drug Administration-approved clinical tools. However, these technologies are still in development for the diagnosis and classification of sleep-disordered breathing.
Tech companies are actively innovating sleep sensing technologies, smartwatches, bed sensors, wireless EEG, radiofrequency, and ultrasound sensors. With significant investments in this sector, these technologies could be ready for widespread use in the next 5 to 10 years. Health care professionals should consider data from sleep-tracking wearables when there are inconsistencies between a patient’s sleep study results and symptoms. The insights from these devices could provide crucial diagnostic information, enhancing the accuracy of sleep disorder diagnoses.
References
1. Ding L, Chen B, Dai Y, Li Y. A meta-analysis of the first-night effect in healthy individuals for the full age spectrum. Sleep Med. 2022;89:159-165. Preprint. Posted online December 17, 2021. PMID: 34998093. doi: 10.1016/j.sleep.2021.12.007
2. Lechat B, Naik G, Reynolds A, et al. Multinight prevalence, variability, and diagnostic misclassification of obstructive sleep apnea. Am J Respir Crit Care Med. 2022;205(5):563-569. PMID: 34904935; PMCID: PMC8906484. doi: 10.1164/rccm.202107-1761OC
3. Abreu A, Punjabi NM. How many nights are really needed to diagnose obstructive sleep apnea? Am J Respir Crit Care Med. 2022;206(1):125-126. PMID: 35476613; PMCID: PMC9954337. doi: 10.1164/rccm.202112-2837LE
Sleep Medicine Network
Respiratory-Related Sleep Disorders Section
Since the 1960s, sleep researchers have been intrigued by the first-night effect (FNE) in polysomnography (PSG) studies. A meta-analysis by Ding and colleagues revealed FNE’s impact on sleep metrics, like total sleep time and REM sleep, without affecting the apnea-hypopnea index, highlighting PSG’s limitations in simulating natural sleep patterns.1
Lechat and colleagues conducted a study using a home-based sleep analyzer on more than 67,000 individuals, averaging 170 nights each.2 This study found that single-night studies could lead to a 20% misdiagnosis rate in OSA, attributed to overlooking real sleep factors such as body posture, environmental effects, alcohol, and medication. Despite this, the wider use of multinight studies for accurate diagnosis is limited by insurance coverage issues.3
The last decade has seen substantial advances in health technology, particularly in consumer wearables capable of detecting various medical conditions. Devices employing techniques like actigraphy and accelerometry have reached a level of performance comparable with US Food and Drug Administration-approved clinical tools. However, these technologies are still in development for the diagnosis and classification of sleep-disordered breathing.
Tech companies are actively innovating sleep sensing technologies, smartwatches, bed sensors, wireless EEG, radiofrequency, and ultrasound sensors. With significant investments in this sector, these technologies could be ready for widespread use in the next 5 to 10 years. Health care professionals should consider data from sleep-tracking wearables when there are inconsistencies between a patient’s sleep study results and symptoms. The insights from these devices could provide crucial diagnostic information, enhancing the accuracy of sleep disorder diagnoses.
References
1. Ding L, Chen B, Dai Y, Li Y. A meta-analysis of the first-night effect in healthy individuals for the full age spectrum. Sleep Med. 2022;89:159-165. Preprint. Posted online December 17, 2021. PMID: 34998093. doi: 10.1016/j.sleep.2021.12.007
2. Lechat B, Naik G, Reynolds A, et al. Multinight prevalence, variability, and diagnostic misclassification of obstructive sleep apnea. Am J Respir Crit Care Med. 2022;205(5):563-569. PMID: 34904935; PMCID: PMC8906484. doi: 10.1164/rccm.202107-1761OC
3. Abreu A, Punjabi NM. How many nights are really needed to diagnose obstructive sleep apnea? Am J Respir Crit Care Med. 2022;206(1):125-126. PMID: 35476613; PMCID: PMC9954337. doi: 10.1164/rccm.202112-2837LE
Novel Treatment Options for Epilepsy
DENVER — , according to new data presented at the 2024 annual meeting of the American Academy of Neurology.
Of the two drugs evaluated in phase 2 trials, one is a highly targeted TARP-8–dependent AMPA receptor antagonist known as ES-481. The other is XEN1101, a novel potassium channel opener that was well tolerated as well as effective.
TARP inhibitors, which act on transmembrane AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) receptor regulatory proteins, are already available for the control of epilepsy, but ES-481 might be different, according to Terrence J. O’Brien, MD, department of neuroscience, Monash University, Melbourne, Australia.
First-in-Class TARP Inhibitor Is Tested
As a “first-in-class, potent and selective antagonist of the TARP-γ8 AMPA receptor,” ES-481 is “predicted to effectively suppress focal seizures arising from the hippocampus and limbic system,” he said. Dr. O’Brien claims that this specificity of action appears to circumvent central nervous system side effects in studies so far.
In the phase 2a multicenter, randomized trial, 22 patients with drug-resistant epilepsy of any type (focal, generalized, or mixed) were randomized to ES-481 or placebo. In the ES-481 arm, the dose was escalated each week, climbing from 25 mg once-daily, to 25 mg twice-daily, 50 mg twice-daily, and then to 75 mg twice daily. At the end of 4 weeks and after a 7-day washout, the randomized groups were crossed over to the opposite therapy for another 4 weeks.
When data were confined to the first treatment period to avoid a carry-over effect, there was a consistent advantage for active treatment over placebo. At the highest 75-mg twice-daily dose of ES-481, the reduction in seizure frequency was 80% vs 49% on placebo ( P < .05).
The rate of complete remission at the end of the study was not greater for ES-481, but higher proportions of patients on active therapy achieved reductions from baseline in seizure activity when defined as greater than 30% (72.77% vs 36.4%) or greater than 50% (36.4% vs 18.2%). P values for these differences were not provided.
Differences in EEG were not observed, but Dr. O’Brien reported that 18 of the subjects had no EEG activity at baseline, diminishing the opportunity to show a difference.
Open-Label Study Supports Controlled Data
Sixteen patients have entered an open-label extension with sustained suppression of seizure activity relative to baseline observed so far, Dr. O’Brien reported.
ES-481 was well tolerated. There were no significant changes in lab values, and all four of the adverse events leading to discontinuation occurred on placebo. There were higher rates of dizziness, insomnia, gait disturbance, and dysarthria associated with ES-481 than placebo, but the rate of serious adverse events was lower (4.8% vs 14.3%).
These response rates are noteworthy because patients had severe disease with diminishing therapeutic options, according to Dr. O’Brien. For entry, patients were required to be taking one to four antiseizure medications while still experiencing seizure activity. The patients averaged one interictal epileptiform discharge and/or seizure per hour on EEG.
Large-scale, double-blind, controlled studies are planned and warranted on the basis of these data, according to Dr. O’Brien, who emphasized that benefit was achieved with a low relative risk of significant adverse events.
New Potassium Channel Opener Shows Promise
Data with the selective potassium channel opener XEN1101 from the previously published phase 2b X-TOLE trial were reported in two parts. The first set of data involved an analysis of response by baseline activity. The other set of data were generated by an ongoing open-label extension (OLE) of X-TOLE.
In X-TOLE, which randomized 325 patients with treatment-resistant focal-onset seizures (FOS) to one of three doses of XEN-1011 or placebo, the median reduction in FOS at the highest dose of 25 mg once-daily XEN-1011 was 52.8% vs placebo (P < .001).
In the new analysis, the goal was to look at efficacy of the 25-mg dose across differences in baseline severity, reported Roger J. Porter, MD, adjunct professor of neurology, University of Pennsylvania, Philadelphia.
Generally, a greater response was observed for those with less severe disease. For example, the response rate defined as greater than 50% reduction in seizure frequency on XEN1101 was higher for those with a baseline seizure activity of 8.5 seizures/month or fewer relative to more (65.5% vs 50.6%) and six or fewer antiseizure medications relative to more (64.2% vs 40.0%).
Pointing out that the study enrolled a challenging group of patients, Dr. Porter said that the data do not rule out efficacy “across the spectrum of epilepsy severity,” but he did suggest that these data will provide context for the coming phase 3 trials.
In the OLE data presented by Jacqueline French, MD, professor of neurology at the Langone School of Medicine of New York University, the efficacy and safety of XEN1101 taken with food has been consistent with what was observed in the double-blind trial. With up to 2 years of follow-up in the planned 5-year OLE, which is evaluating 20 mg once-daily taken with food, 60% are still on therapy,
For those followed for 24 months, 23.6% are completely seizure free, according to Dr. French. For those followed at least 12 months, 31.5% have achieved a median percent reduction in monthly seizure activity of 90% or more; 41.8% a reduction of 75% or more; and 69.7% a reduction of 50% or more.
The side-effect profile has also been consistent with that seen in the phase 2b trial. Dizziness and other mild to moderate side effects that often accompany antiseizure medications have been observed, along with modest weight gain, but there have been no new safety signals over long-term use.
If a planned phase 3 study enrolling patients with localized and general epilepsy confirms these phase 2 data, Dr. French indicated that it has the potential to advance a potassium channel opener that is both efficacious and well tolerated.
First-in-Man Study Performed With Stem Cell Product
The investigational product for treatment-resistant epilepsy has data on just five patients. Yet, the two patients followed the longest, both of which had highly treatment-resistant epilepsy, have had reductions in seizure activity exceeding 95%, according to Cory Nicholas, PhD, the chief executive officer of Neurona Therapeutics.
NRTX-100 is a GABAergic interneuron product derived from human pluripotent stem cells. The NRTX cells are surgically transplanted into the head and body of the hippocampus in patients with unilateral temporal lobe epilepsy with hippocampal sclerosis. The procedure is performed with MRI guidance, and patients are placed on immunosuppression that starts 1 week before surgery and is tapered 1 year later.
In this first-in-man study, the primary outcome of interest was safety. There have been no adverse events associated with this stem cell product in follow-up so far, according to Dr. Nicholas, who presented data on the first 5 of 10 procedures that have been completed so far.
Consistent with the prior work in animal models, it takes several months for the reduction in seizures to be achieved and, in animal models, to see improved functionality. It is notable that the reductions in seizure activity observed over time in those patients followed the longest have been accompanied by evidence of neurocognitive improvement, Dr. Nicholas reported.
“The efficacy has seemed durable so far, and we expect incremental improvement in clinical response over time,” said Dr. Nicholas, who reported that the Food and Drug Administration has already approved a second clinical study.
Are New Antiseizure Therapies Needed?
The value of this and the other emerging therapies is that “no treatment for epilepsy works well in every patient. We continue to need a wide array of treatments to find the one right for the patient in front of us,” said Nassim Zecavati, MD, director of Epilepsy, Children’s Hospital, Virginia Commonwealth University, Richmond.
Asked to comment on the promise of these three therapies, Dr. Zecavati suggested each is intriguing for different reasons. AMPA receptor antagonists have proven to be a promising drug class so far, suggesting that “another could be helpful.” Potassium channel openers appear to have “a great mechanism of action,” but Dr. Zecavati said drugs in this class with a more favorable safety profile are needed.
As for NRTX-1001, she was intrigued with its novelty. She speculated that it might have particular promise for intractable drug-resistant epilepsy in patients who are not candidates for standard surgical strategies but might tolerate a less invasive procedure.
“My question might be who is going to perform this procedure,” Dr. Zecavati said. Noting that experience and skill might be needed to achieve an optimal result with cell transplantation into the brain, she said she will be waiting for more studies that might answer this question and to determine where, if effective, it would fit among current options.
Dr. O’Brien reported financial relationships with Eisai, Kinoxis, Livanova, Supernus, and UCB Pharma. Dr. Porter reported financial relationships with Axonis, Engrail, Longboard, Neurocrine, and Xenon, which provided funding for the study he discussed. Dr. French has financial relationships with more than 20 pharmaceutical companies, including Xenon, which provided funding for the study she discussed. Dr. Nicholas is chief executive officer of Neurona Therapeutics. Dr. Zecavati reported no potential conflicts of interest.
DENVER — , according to new data presented at the 2024 annual meeting of the American Academy of Neurology.
Of the two drugs evaluated in phase 2 trials, one is a highly targeted TARP-8–dependent AMPA receptor antagonist known as ES-481. The other is XEN1101, a novel potassium channel opener that was well tolerated as well as effective.
TARP inhibitors, which act on transmembrane AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) receptor regulatory proteins, are already available for the control of epilepsy, but ES-481 might be different, according to Terrence J. O’Brien, MD, department of neuroscience, Monash University, Melbourne, Australia.
First-in-Class TARP Inhibitor Is Tested
As a “first-in-class, potent and selective antagonist of the TARP-γ8 AMPA receptor,” ES-481 is “predicted to effectively suppress focal seizures arising from the hippocampus and limbic system,” he said. Dr. O’Brien claims that this specificity of action appears to circumvent central nervous system side effects in studies so far.
In the phase 2a multicenter, randomized trial, 22 patients with drug-resistant epilepsy of any type (focal, generalized, or mixed) were randomized to ES-481 or placebo. In the ES-481 arm, the dose was escalated each week, climbing from 25 mg once-daily, to 25 mg twice-daily, 50 mg twice-daily, and then to 75 mg twice daily. At the end of 4 weeks and after a 7-day washout, the randomized groups were crossed over to the opposite therapy for another 4 weeks.
When data were confined to the first treatment period to avoid a carry-over effect, there was a consistent advantage for active treatment over placebo. At the highest 75-mg twice-daily dose of ES-481, the reduction in seizure frequency was 80% vs 49% on placebo ( P < .05).
The rate of complete remission at the end of the study was not greater for ES-481, but higher proportions of patients on active therapy achieved reductions from baseline in seizure activity when defined as greater than 30% (72.77% vs 36.4%) or greater than 50% (36.4% vs 18.2%). P values for these differences were not provided.
Differences in EEG were not observed, but Dr. O’Brien reported that 18 of the subjects had no EEG activity at baseline, diminishing the opportunity to show a difference.
Open-Label Study Supports Controlled Data
Sixteen patients have entered an open-label extension with sustained suppression of seizure activity relative to baseline observed so far, Dr. O’Brien reported.
ES-481 was well tolerated. There were no significant changes in lab values, and all four of the adverse events leading to discontinuation occurred on placebo. There were higher rates of dizziness, insomnia, gait disturbance, and dysarthria associated with ES-481 than placebo, but the rate of serious adverse events was lower (4.8% vs 14.3%).
These response rates are noteworthy because patients had severe disease with diminishing therapeutic options, according to Dr. O’Brien. For entry, patients were required to be taking one to four antiseizure medications while still experiencing seizure activity. The patients averaged one interictal epileptiform discharge and/or seizure per hour on EEG.
Large-scale, double-blind, controlled studies are planned and warranted on the basis of these data, according to Dr. O’Brien, who emphasized that benefit was achieved with a low relative risk of significant adverse events.
New Potassium Channel Opener Shows Promise
Data with the selective potassium channel opener XEN1101 from the previously published phase 2b X-TOLE trial were reported in two parts. The first set of data involved an analysis of response by baseline activity. The other set of data were generated by an ongoing open-label extension (OLE) of X-TOLE.
In X-TOLE, which randomized 325 patients with treatment-resistant focal-onset seizures (FOS) to one of three doses of XEN-1011 or placebo, the median reduction in FOS at the highest dose of 25 mg once-daily XEN-1011 was 52.8% vs placebo (P < .001).
In the new analysis, the goal was to look at efficacy of the 25-mg dose across differences in baseline severity, reported Roger J. Porter, MD, adjunct professor of neurology, University of Pennsylvania, Philadelphia.
Generally, a greater response was observed for those with less severe disease. For example, the response rate defined as greater than 50% reduction in seizure frequency on XEN1101 was higher for those with a baseline seizure activity of 8.5 seizures/month or fewer relative to more (65.5% vs 50.6%) and six or fewer antiseizure medications relative to more (64.2% vs 40.0%).
Pointing out that the study enrolled a challenging group of patients, Dr. Porter said that the data do not rule out efficacy “across the spectrum of epilepsy severity,” but he did suggest that these data will provide context for the coming phase 3 trials.
In the OLE data presented by Jacqueline French, MD, professor of neurology at the Langone School of Medicine of New York University, the efficacy and safety of XEN1101 taken with food has been consistent with what was observed in the double-blind trial. With up to 2 years of follow-up in the planned 5-year OLE, which is evaluating 20 mg once-daily taken with food, 60% are still on therapy,
For those followed for 24 months, 23.6% are completely seizure free, according to Dr. French. For those followed at least 12 months, 31.5% have achieved a median percent reduction in monthly seizure activity of 90% or more; 41.8% a reduction of 75% or more; and 69.7% a reduction of 50% or more.
The side-effect profile has also been consistent with that seen in the phase 2b trial. Dizziness and other mild to moderate side effects that often accompany antiseizure medications have been observed, along with modest weight gain, but there have been no new safety signals over long-term use.
If a planned phase 3 study enrolling patients with localized and general epilepsy confirms these phase 2 data, Dr. French indicated that it has the potential to advance a potassium channel opener that is both efficacious and well tolerated.
First-in-Man Study Performed With Stem Cell Product
The investigational product for treatment-resistant epilepsy has data on just five patients. Yet, the two patients followed the longest, both of which had highly treatment-resistant epilepsy, have had reductions in seizure activity exceeding 95%, according to Cory Nicholas, PhD, the chief executive officer of Neurona Therapeutics.
NRTX-100 is a GABAergic interneuron product derived from human pluripotent stem cells. The NRTX cells are surgically transplanted into the head and body of the hippocampus in patients with unilateral temporal lobe epilepsy with hippocampal sclerosis. The procedure is performed with MRI guidance, and patients are placed on immunosuppression that starts 1 week before surgery and is tapered 1 year later.
In this first-in-man study, the primary outcome of interest was safety. There have been no adverse events associated with this stem cell product in follow-up so far, according to Dr. Nicholas, who presented data on the first 5 of 10 procedures that have been completed so far.
Consistent with the prior work in animal models, it takes several months for the reduction in seizures to be achieved and, in animal models, to see improved functionality. It is notable that the reductions in seizure activity observed over time in those patients followed the longest have been accompanied by evidence of neurocognitive improvement, Dr. Nicholas reported.
“The efficacy has seemed durable so far, and we expect incremental improvement in clinical response over time,” said Dr. Nicholas, who reported that the Food and Drug Administration has already approved a second clinical study.
Are New Antiseizure Therapies Needed?
The value of this and the other emerging therapies is that “no treatment for epilepsy works well in every patient. We continue to need a wide array of treatments to find the one right for the patient in front of us,” said Nassim Zecavati, MD, director of Epilepsy, Children’s Hospital, Virginia Commonwealth University, Richmond.
Asked to comment on the promise of these three therapies, Dr. Zecavati suggested each is intriguing for different reasons. AMPA receptor antagonists have proven to be a promising drug class so far, suggesting that “another could be helpful.” Potassium channel openers appear to have “a great mechanism of action,” but Dr. Zecavati said drugs in this class with a more favorable safety profile are needed.
As for NRTX-1001, she was intrigued with its novelty. She speculated that it might have particular promise for intractable drug-resistant epilepsy in patients who are not candidates for standard surgical strategies but might tolerate a less invasive procedure.
“My question might be who is going to perform this procedure,” Dr. Zecavati said. Noting that experience and skill might be needed to achieve an optimal result with cell transplantation into the brain, she said she will be waiting for more studies that might answer this question and to determine where, if effective, it would fit among current options.
Dr. O’Brien reported financial relationships with Eisai, Kinoxis, Livanova, Supernus, and UCB Pharma. Dr. Porter reported financial relationships with Axonis, Engrail, Longboard, Neurocrine, and Xenon, which provided funding for the study he discussed. Dr. French has financial relationships with more than 20 pharmaceutical companies, including Xenon, which provided funding for the study she discussed. Dr. Nicholas is chief executive officer of Neurona Therapeutics. Dr. Zecavati reported no potential conflicts of interest.
DENVER — , according to new data presented at the 2024 annual meeting of the American Academy of Neurology.
Of the two drugs evaluated in phase 2 trials, one is a highly targeted TARP-8–dependent AMPA receptor antagonist known as ES-481. The other is XEN1101, a novel potassium channel opener that was well tolerated as well as effective.
TARP inhibitors, which act on transmembrane AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) receptor regulatory proteins, are already available for the control of epilepsy, but ES-481 might be different, according to Terrence J. O’Brien, MD, department of neuroscience, Monash University, Melbourne, Australia.
First-in-Class TARP Inhibitor Is Tested
As a “first-in-class, potent and selective antagonist of the TARP-γ8 AMPA receptor,” ES-481 is “predicted to effectively suppress focal seizures arising from the hippocampus and limbic system,” he said. Dr. O’Brien claims that this specificity of action appears to circumvent central nervous system side effects in studies so far.
In the phase 2a multicenter, randomized trial, 22 patients with drug-resistant epilepsy of any type (focal, generalized, or mixed) were randomized to ES-481 or placebo. In the ES-481 arm, the dose was escalated each week, climbing from 25 mg once-daily, to 25 mg twice-daily, 50 mg twice-daily, and then to 75 mg twice daily. At the end of 4 weeks and after a 7-day washout, the randomized groups were crossed over to the opposite therapy for another 4 weeks.
When data were confined to the first treatment period to avoid a carry-over effect, there was a consistent advantage for active treatment over placebo. At the highest 75-mg twice-daily dose of ES-481, the reduction in seizure frequency was 80% vs 49% on placebo ( P < .05).
The rate of complete remission at the end of the study was not greater for ES-481, but higher proportions of patients on active therapy achieved reductions from baseline in seizure activity when defined as greater than 30% (72.77% vs 36.4%) or greater than 50% (36.4% vs 18.2%). P values for these differences were not provided.
Differences in EEG were not observed, but Dr. O’Brien reported that 18 of the subjects had no EEG activity at baseline, diminishing the opportunity to show a difference.
Open-Label Study Supports Controlled Data
Sixteen patients have entered an open-label extension with sustained suppression of seizure activity relative to baseline observed so far, Dr. O’Brien reported.
ES-481 was well tolerated. There were no significant changes in lab values, and all four of the adverse events leading to discontinuation occurred on placebo. There were higher rates of dizziness, insomnia, gait disturbance, and dysarthria associated with ES-481 than placebo, but the rate of serious adverse events was lower (4.8% vs 14.3%).
These response rates are noteworthy because patients had severe disease with diminishing therapeutic options, according to Dr. O’Brien. For entry, patients were required to be taking one to four antiseizure medications while still experiencing seizure activity. The patients averaged one interictal epileptiform discharge and/or seizure per hour on EEG.
Large-scale, double-blind, controlled studies are planned and warranted on the basis of these data, according to Dr. O’Brien, who emphasized that benefit was achieved with a low relative risk of significant adverse events.
New Potassium Channel Opener Shows Promise
Data with the selective potassium channel opener XEN1101 from the previously published phase 2b X-TOLE trial were reported in two parts. The first set of data involved an analysis of response by baseline activity. The other set of data were generated by an ongoing open-label extension (OLE) of X-TOLE.
In X-TOLE, which randomized 325 patients with treatment-resistant focal-onset seizures (FOS) to one of three doses of XEN-1011 or placebo, the median reduction in FOS at the highest dose of 25 mg once-daily XEN-1011 was 52.8% vs placebo (P < .001).
In the new analysis, the goal was to look at efficacy of the 25-mg dose across differences in baseline severity, reported Roger J. Porter, MD, adjunct professor of neurology, University of Pennsylvania, Philadelphia.
Generally, a greater response was observed for those with less severe disease. For example, the response rate defined as greater than 50% reduction in seizure frequency on XEN1101 was higher for those with a baseline seizure activity of 8.5 seizures/month or fewer relative to more (65.5% vs 50.6%) and six or fewer antiseizure medications relative to more (64.2% vs 40.0%).
Pointing out that the study enrolled a challenging group of patients, Dr. Porter said that the data do not rule out efficacy “across the spectrum of epilepsy severity,” but he did suggest that these data will provide context for the coming phase 3 trials.
In the OLE data presented by Jacqueline French, MD, professor of neurology at the Langone School of Medicine of New York University, the efficacy and safety of XEN1101 taken with food has been consistent with what was observed in the double-blind trial. With up to 2 years of follow-up in the planned 5-year OLE, which is evaluating 20 mg once-daily taken with food, 60% are still on therapy,
For those followed for 24 months, 23.6% are completely seizure free, according to Dr. French. For those followed at least 12 months, 31.5% have achieved a median percent reduction in monthly seizure activity of 90% or more; 41.8% a reduction of 75% or more; and 69.7% a reduction of 50% or more.
The side-effect profile has also been consistent with that seen in the phase 2b trial. Dizziness and other mild to moderate side effects that often accompany antiseizure medications have been observed, along with modest weight gain, but there have been no new safety signals over long-term use.
If a planned phase 3 study enrolling patients with localized and general epilepsy confirms these phase 2 data, Dr. French indicated that it has the potential to advance a potassium channel opener that is both efficacious and well tolerated.
First-in-Man Study Performed With Stem Cell Product
The investigational product for treatment-resistant epilepsy has data on just five patients. Yet, the two patients followed the longest, both of which had highly treatment-resistant epilepsy, have had reductions in seizure activity exceeding 95%, according to Cory Nicholas, PhD, the chief executive officer of Neurona Therapeutics.
NRTX-100 is a GABAergic interneuron product derived from human pluripotent stem cells. The NRTX cells are surgically transplanted into the head and body of the hippocampus in patients with unilateral temporal lobe epilepsy with hippocampal sclerosis. The procedure is performed with MRI guidance, and patients are placed on immunosuppression that starts 1 week before surgery and is tapered 1 year later.
In this first-in-man study, the primary outcome of interest was safety. There have been no adverse events associated with this stem cell product in follow-up so far, according to Dr. Nicholas, who presented data on the first 5 of 10 procedures that have been completed so far.
Consistent with the prior work in animal models, it takes several months for the reduction in seizures to be achieved and, in animal models, to see improved functionality. It is notable that the reductions in seizure activity observed over time in those patients followed the longest have been accompanied by evidence of neurocognitive improvement, Dr. Nicholas reported.
“The efficacy has seemed durable so far, and we expect incremental improvement in clinical response over time,” said Dr. Nicholas, who reported that the Food and Drug Administration has already approved a second clinical study.
Are New Antiseizure Therapies Needed?
The value of this and the other emerging therapies is that “no treatment for epilepsy works well in every patient. We continue to need a wide array of treatments to find the one right for the patient in front of us,” said Nassim Zecavati, MD, director of Epilepsy, Children’s Hospital, Virginia Commonwealth University, Richmond.
Asked to comment on the promise of these three therapies, Dr. Zecavati suggested each is intriguing for different reasons. AMPA receptor antagonists have proven to be a promising drug class so far, suggesting that “another could be helpful.” Potassium channel openers appear to have “a great mechanism of action,” but Dr. Zecavati said drugs in this class with a more favorable safety profile are needed.
As for NRTX-1001, she was intrigued with its novelty. She speculated that it might have particular promise for intractable drug-resistant epilepsy in patients who are not candidates for standard surgical strategies but might tolerate a less invasive procedure.
“My question might be who is going to perform this procedure,” Dr. Zecavati said. Noting that experience and skill might be needed to achieve an optimal result with cell transplantation into the brain, she said she will be waiting for more studies that might answer this question and to determine where, if effective, it would fit among current options.
Dr. O’Brien reported financial relationships with Eisai, Kinoxis, Livanova, Supernus, and UCB Pharma. Dr. Porter reported financial relationships with Axonis, Engrail, Longboard, Neurocrine, and Xenon, which provided funding for the study he discussed. Dr. French has financial relationships with more than 20 pharmaceutical companies, including Xenon, which provided funding for the study she discussed. Dr. Nicholas is chief executive officer of Neurona Therapeutics. Dr. Zecavati reported no potential conflicts of interest.
FROM AAN 2024
MicroRNAs May Predict Pancreatic Cancer Risk Years Before Diagnosis
TOPLINE:
METHODOLOGY:
- Early detection of pancreatic cancer could improve patient prognosis, but clinically viable biomarkers are lacking. In a two-stage study, researchers screened and validated circulating miRNAs as biomarkers for early detection using prediagnostic plasma samples from 462 case-control pairs across multiple cohorts.
- The discovery stage included 185 pairs from the PLCO Cancer Screening Trial, and the replication stage included 277 pairs from Shanghai Women’s/Men’s Health Study, Southern Community Cohort Study, and Multiethnic Cohort Study.
- Overall, 798 plasma microRNAs were measured using the NanoString nCounter Analysis System, and odds ratios (ORs) for pancreatic cancer risk were calculated on the basis of miRNA concentrations.
- Statistical analysis involved conditional logistic regression, stratified by age and time from sample collection to diagnosis.
TAKEAWAY:
- In the discovery stage, the researchers identified 120 miRNAs significantly associated with pancreatic cancer risk.
- Three of these miRNAs showed consistent significant associations in the replication stage. Specifically, hsa-miR-199a-3p/hsa-miR-199b-3p and hsa-miR-191-5p were associated with a 10%-11% lower risk for pancreatic cancer (OR, 0.89 and 0.90, respectively), and hsa-miR-767-5p was associated with an 8% higher risk for pancreatic cancer (OR, 1.08) within 5 years of the blood draw.
- In age-stratified analyses, hsa-miR-767-5p (OR, 1.23) along with four other miRNAs — hsa-miR-640 (OR, 1.33), hsa-miR-874-5p (OR, 1.25), hsa-miR-1299 (OR, 1.28), and hsa-miR-449b-5p (OR, 1.22) — were associated with an increased risk for pancreatic cancer among patients diagnosed at age 65 or older.
- One miRNA, hsa-miR-22-3p (OR, 0.76), was associated with a lower risk for pancreatic cancer in this older age group.
IN PRACTICE:
The findings provide evidence that miRNAs “have a potential utilization in clinical practice” to help “identify high-risk individuals who could subsequently undergo a more definitive but invasive diagnostic procedure,” the authors said. “Such a multistep strategy for pancreatic cancer screening and early detection, likely cost-efficient and low-risk, could be critical to improve survival.”
SOURCE:
The study, with first author Cong Wang, Vanderbilt University Medical Center, Nashville, Tennessee, was published online in the International Journal of Cancer.
LIMITATIONS:
The researchers lacked miRNA profiles of patients with pancreatic cancer at diagnosis and were not able to track the miRNA changes among pancreatic cancer cases at the time of clinical diagnosis. Sample collection protocols differed across study cohorts, and the researchers changed assay panels during the study.
DISCLOSURES:
The research was funded by grants from the National Cancer Institute. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Early detection of pancreatic cancer could improve patient prognosis, but clinically viable biomarkers are lacking. In a two-stage study, researchers screened and validated circulating miRNAs as biomarkers for early detection using prediagnostic plasma samples from 462 case-control pairs across multiple cohorts.
- The discovery stage included 185 pairs from the PLCO Cancer Screening Trial, and the replication stage included 277 pairs from Shanghai Women’s/Men’s Health Study, Southern Community Cohort Study, and Multiethnic Cohort Study.
- Overall, 798 plasma microRNAs were measured using the NanoString nCounter Analysis System, and odds ratios (ORs) for pancreatic cancer risk were calculated on the basis of miRNA concentrations.
- Statistical analysis involved conditional logistic regression, stratified by age and time from sample collection to diagnosis.
TAKEAWAY:
- In the discovery stage, the researchers identified 120 miRNAs significantly associated with pancreatic cancer risk.
- Three of these miRNAs showed consistent significant associations in the replication stage. Specifically, hsa-miR-199a-3p/hsa-miR-199b-3p and hsa-miR-191-5p were associated with a 10%-11% lower risk for pancreatic cancer (OR, 0.89 and 0.90, respectively), and hsa-miR-767-5p was associated with an 8% higher risk for pancreatic cancer (OR, 1.08) within 5 years of the blood draw.
- In age-stratified analyses, hsa-miR-767-5p (OR, 1.23) along with four other miRNAs — hsa-miR-640 (OR, 1.33), hsa-miR-874-5p (OR, 1.25), hsa-miR-1299 (OR, 1.28), and hsa-miR-449b-5p (OR, 1.22) — were associated with an increased risk for pancreatic cancer among patients diagnosed at age 65 or older.
- One miRNA, hsa-miR-22-3p (OR, 0.76), was associated with a lower risk for pancreatic cancer in this older age group.
IN PRACTICE:
The findings provide evidence that miRNAs “have a potential utilization in clinical practice” to help “identify high-risk individuals who could subsequently undergo a more definitive but invasive diagnostic procedure,” the authors said. “Such a multistep strategy for pancreatic cancer screening and early detection, likely cost-efficient and low-risk, could be critical to improve survival.”
SOURCE:
The study, with first author Cong Wang, Vanderbilt University Medical Center, Nashville, Tennessee, was published online in the International Journal of Cancer.
LIMITATIONS:
The researchers lacked miRNA profiles of patients with pancreatic cancer at diagnosis and were not able to track the miRNA changes among pancreatic cancer cases at the time of clinical diagnosis. Sample collection protocols differed across study cohorts, and the researchers changed assay panels during the study.
DISCLOSURES:
The research was funded by grants from the National Cancer Institute. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Early detection of pancreatic cancer could improve patient prognosis, but clinically viable biomarkers are lacking. In a two-stage study, researchers screened and validated circulating miRNAs as biomarkers for early detection using prediagnostic plasma samples from 462 case-control pairs across multiple cohorts.
- The discovery stage included 185 pairs from the PLCO Cancer Screening Trial, and the replication stage included 277 pairs from Shanghai Women’s/Men’s Health Study, Southern Community Cohort Study, and Multiethnic Cohort Study.
- Overall, 798 plasma microRNAs were measured using the NanoString nCounter Analysis System, and odds ratios (ORs) for pancreatic cancer risk were calculated on the basis of miRNA concentrations.
- Statistical analysis involved conditional logistic regression, stratified by age and time from sample collection to diagnosis.
TAKEAWAY:
- In the discovery stage, the researchers identified 120 miRNAs significantly associated with pancreatic cancer risk.
- Three of these miRNAs showed consistent significant associations in the replication stage. Specifically, hsa-miR-199a-3p/hsa-miR-199b-3p and hsa-miR-191-5p were associated with a 10%-11% lower risk for pancreatic cancer (OR, 0.89 and 0.90, respectively), and hsa-miR-767-5p was associated with an 8% higher risk for pancreatic cancer (OR, 1.08) within 5 years of the blood draw.
- In age-stratified analyses, hsa-miR-767-5p (OR, 1.23) along with four other miRNAs — hsa-miR-640 (OR, 1.33), hsa-miR-874-5p (OR, 1.25), hsa-miR-1299 (OR, 1.28), and hsa-miR-449b-5p (OR, 1.22) — were associated with an increased risk for pancreatic cancer among patients diagnosed at age 65 or older.
- One miRNA, hsa-miR-22-3p (OR, 0.76), was associated with a lower risk for pancreatic cancer in this older age group.
IN PRACTICE:
The findings provide evidence that miRNAs “have a potential utilization in clinical practice” to help “identify high-risk individuals who could subsequently undergo a more definitive but invasive diagnostic procedure,” the authors said. “Such a multistep strategy for pancreatic cancer screening and early detection, likely cost-efficient and low-risk, could be critical to improve survival.”
SOURCE:
The study, with first author Cong Wang, Vanderbilt University Medical Center, Nashville, Tennessee, was published online in the International Journal of Cancer.
LIMITATIONS:
The researchers lacked miRNA profiles of patients with pancreatic cancer at diagnosis and were not able to track the miRNA changes among pancreatic cancer cases at the time of clinical diagnosis. Sample collection protocols differed across study cohorts, and the researchers changed assay panels during the study.
DISCLOSURES:
The research was funded by grants from the National Cancer Institute. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
‘Bread and Butter’: Societies Issue T2D Management Guidance
Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.
On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors.
The document was also presented simultaneously at the ACP annual meeting.
And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
General Agreement but Some Differences
The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone.
The new ACP document gives two general recommendations:
1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control.
*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.
*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.
2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.
Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.
ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.”
The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely.
This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”
Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.”
In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness.
In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”
Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”
However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.
“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”
Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.
A version of this article first appeared on Medscape.com.
Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.
On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors.
The document was also presented simultaneously at the ACP annual meeting.
And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
General Agreement but Some Differences
The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone.
The new ACP document gives two general recommendations:
1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control.
*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.
*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.
2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.
Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.
ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.”
The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely.
This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”
Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.”
In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness.
In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”
Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”
However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.
“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”
Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.
A version of this article first appeared on Medscape.com.
Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.
On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors.
The document was also presented simultaneously at the ACP annual meeting.
And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
General Agreement but Some Differences
The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone.
The new ACP document gives two general recommendations:
1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control.
*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.
*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.
2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.
Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.
ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.”
The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely.
This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”
Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.”
In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness.
In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”
Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”
However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.
“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”
Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.
A version of this article first appeared on Medscape.com.
Pediatric Clinic Doubles Well-Visit Data Capture by Going Completely Paperless
TORONTO — , and, of course, it eliminated the work associated with managing paper records.
Due to the efficacy of the pre-visit capture, “all of the information — including individual responses and total scores — is available to the provider at a glance” by the time of the examination encounter, according to Brian T. Ketterman, MD, a third-year resident in pediatrics at the Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tennessee.
Urgent issues, such as suicidality risk, “are flagged so that they are seen first,” he added.
The goal of going paperless was to improve the amount and the consistency of data captured with each well visit, according to Dr. Ketterman. He described a major undertaking involving fundamental changes in the electronic medical record (EMR) system to accommodate the new approach.
Characterizing screening at well visits as “one of the most important jobs of a pediatrician” when he presented these data at the Pediatric Academic Societies annual meeting, he added that a paperless approach comes with many advantages.
Raising the Rate of Complete Data Capture
The American Academy of Pediatrics (AAP) has identified more than 30 screening elements at well-child visits. At his institution several additional screening elements have been added. Prior to going paperless, about 45.6% on average of this well-visit data was being captured in any specific patient encounter, even if the institution was doing well overall in capturing essential information, such as key laboratory values and immunizations.
The vast majority of the information that was missing depended on patient or family input, such as social determinants of health (SDoH), which includes the aspects of home environment, such as nutrition and safety. Dr. Ketterman said that going paperless was inspired by positive experiences reported elsewhere.
“We wanted to build on this work,” he said.
The goal of the program was to raise the rate of complete data capture at well visits to at least 80% and do this across all languages. The first step was to create digital forms in English and Spanish for completion unique to each milestone well-child visit defined by age. For those who speak English or Spanish, these forms were supplied through the patient portal several days before the visit.
For those who spoke one of the more than 40 other languages encountered among patients at Dr. Ketterman’s institution, an interpreter was supplied. If patients arrived at the clinic without completing the digital entry, they completed it on a tablet with the help of an interpreter if one was needed.
Prior to going paperless, all screening data were captured on paper forms completed in the waiting room. The provider then manually reviewed and scored the forms before they were then scanned into the medical records. The paperless approach has eliminated all of these steps and the information is already available for review by the time the pediatrician enters the examination room.
With more than 50,000 well-child checkups captured over a recent 15-month period of paperless questionnaires, the proportion with 100% data capture using what Dr. Ketterman characterized as “strict criteria” was 84%, surpassing the goal at the initiation of the program.
“We improved in almost every screening measure,” Dr. Ketterman said, providing P values that were mostly < .001 for a range of standard tests such as M-CHAT-R (Modified Checklist for Autism in Toddlers), QPA (Quick Parenting Assessment), and PSC-17 (Pediatric Symptom Checklist) when compared to the baseline period.
Additional Advantages
The improvement in well-visit data capture was the goal, but the list of other advantages of the paperless system is long. For one, the EMR system now automatically uses the data to offer guidance that might improve patient outcomes. For example, if the family reports that the child does not see a dentist or does not know how to swim, these lead prompt the EMR to provide resources, such as the names of dentists of swim programs, to address the problem.
As another example, screening questions that reveal food insecurity automatically trigger guidance for enrolling in the U.S. Department of Agriculture’s WIC (Women, Infants, and Children) food program. According to Dr. Ketterman, the proportion of children now enrolled in WIC has increased 10-fold from baseline. He also reported there was a twofold increase in the proportion of patients enrolled in a free book program as a result of a screening questions that ask about reading at home.
The improvement in well-visit data capture was seen across all languages. Even if the gains were not quite as good in languages other than English or Spanish, they were still highly significant relative to baseline.
A ‘Life-Changing’ Improvement
The discussion following his talk made it clear that similar approaches are being actively pursued nationwide. Several in the audience working on similar programs identified such challenges as getting electronic medical record (EMR) systems to cooperate, ensuring patient enrollment in the portals, and avoiding form completion fatigue, but the comments were uniformly supportive of the benefits of this approach.
“This has been life-changing for us,” said Katie E. McPeak, MD, a primary care pediatrician and Medical Director for Health Equity at the Children’s Hospital of Philadelphia. “The information is more accurate in the digital format and it reduces time for the clinician reviewing the data in the exam room.” She also agreed that paperless completion of screen captures better information on more topics, like sleep, nutrition, and mood disorders.
However, Dr. McPeak was one of those who was concerned about form fatigue. Patients have to enter extensive information over multiple screens for each well-child visit. She said this problem might need to be addressed if the success of paperless screening leads to even greater expansion of data requested.
In addressing the work behind creating a system of the depth and scope of the one he described, Dr. Ketterman acknowledged that it involved a daunting development process with substantial coding and testing. Referring to the EMR system used at his hospital, he said the preparation required an “epic guru,” but he said that input fatigue has not yet arisen as a major issue.
“Many of the screens are mandatory, so you cannot advance without completing them, but some are optional,” he noted. “However, we are seeing a high rate of response even on the screens they could click past.”
Dr. Ketterman and Dr. McPeak report no potential conflicts of interest.
TORONTO — , and, of course, it eliminated the work associated with managing paper records.
Due to the efficacy of the pre-visit capture, “all of the information — including individual responses and total scores — is available to the provider at a glance” by the time of the examination encounter, according to Brian T. Ketterman, MD, a third-year resident in pediatrics at the Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tennessee.
Urgent issues, such as suicidality risk, “are flagged so that they are seen first,” he added.
The goal of going paperless was to improve the amount and the consistency of data captured with each well visit, according to Dr. Ketterman. He described a major undertaking involving fundamental changes in the electronic medical record (EMR) system to accommodate the new approach.
Characterizing screening at well visits as “one of the most important jobs of a pediatrician” when he presented these data at the Pediatric Academic Societies annual meeting, he added that a paperless approach comes with many advantages.
Raising the Rate of Complete Data Capture
The American Academy of Pediatrics (AAP) has identified more than 30 screening elements at well-child visits. At his institution several additional screening elements have been added. Prior to going paperless, about 45.6% on average of this well-visit data was being captured in any specific patient encounter, even if the institution was doing well overall in capturing essential information, such as key laboratory values and immunizations.
The vast majority of the information that was missing depended on patient or family input, such as social determinants of health (SDoH), which includes the aspects of home environment, such as nutrition and safety. Dr. Ketterman said that going paperless was inspired by positive experiences reported elsewhere.
“We wanted to build on this work,” he said.
The goal of the program was to raise the rate of complete data capture at well visits to at least 80% and do this across all languages. The first step was to create digital forms in English and Spanish for completion unique to each milestone well-child visit defined by age. For those who speak English or Spanish, these forms were supplied through the patient portal several days before the visit.
For those who spoke one of the more than 40 other languages encountered among patients at Dr. Ketterman’s institution, an interpreter was supplied. If patients arrived at the clinic without completing the digital entry, they completed it on a tablet with the help of an interpreter if one was needed.
Prior to going paperless, all screening data were captured on paper forms completed in the waiting room. The provider then manually reviewed and scored the forms before they were then scanned into the medical records. The paperless approach has eliminated all of these steps and the information is already available for review by the time the pediatrician enters the examination room.
With more than 50,000 well-child checkups captured over a recent 15-month period of paperless questionnaires, the proportion with 100% data capture using what Dr. Ketterman characterized as “strict criteria” was 84%, surpassing the goal at the initiation of the program.
“We improved in almost every screening measure,” Dr. Ketterman said, providing P values that were mostly < .001 for a range of standard tests such as M-CHAT-R (Modified Checklist for Autism in Toddlers), QPA (Quick Parenting Assessment), and PSC-17 (Pediatric Symptom Checklist) when compared to the baseline period.
Additional Advantages
The improvement in well-visit data capture was the goal, but the list of other advantages of the paperless system is long. For one, the EMR system now automatically uses the data to offer guidance that might improve patient outcomes. For example, if the family reports that the child does not see a dentist or does not know how to swim, these lead prompt the EMR to provide resources, such as the names of dentists of swim programs, to address the problem.
As another example, screening questions that reveal food insecurity automatically trigger guidance for enrolling in the U.S. Department of Agriculture’s WIC (Women, Infants, and Children) food program. According to Dr. Ketterman, the proportion of children now enrolled in WIC has increased 10-fold from baseline. He also reported there was a twofold increase in the proportion of patients enrolled in a free book program as a result of a screening questions that ask about reading at home.
The improvement in well-visit data capture was seen across all languages. Even if the gains were not quite as good in languages other than English or Spanish, they were still highly significant relative to baseline.
A ‘Life-Changing’ Improvement
The discussion following his talk made it clear that similar approaches are being actively pursued nationwide. Several in the audience working on similar programs identified such challenges as getting electronic medical record (EMR) systems to cooperate, ensuring patient enrollment in the portals, and avoiding form completion fatigue, but the comments were uniformly supportive of the benefits of this approach.
“This has been life-changing for us,” said Katie E. McPeak, MD, a primary care pediatrician and Medical Director for Health Equity at the Children’s Hospital of Philadelphia. “The information is more accurate in the digital format and it reduces time for the clinician reviewing the data in the exam room.” She also agreed that paperless completion of screen captures better information on more topics, like sleep, nutrition, and mood disorders.
However, Dr. McPeak was one of those who was concerned about form fatigue. Patients have to enter extensive information over multiple screens for each well-child visit. She said this problem might need to be addressed if the success of paperless screening leads to even greater expansion of data requested.
In addressing the work behind creating a system of the depth and scope of the one he described, Dr. Ketterman acknowledged that it involved a daunting development process with substantial coding and testing. Referring to the EMR system used at his hospital, he said the preparation required an “epic guru,” but he said that input fatigue has not yet arisen as a major issue.
“Many of the screens are mandatory, so you cannot advance without completing them, but some are optional,” he noted. “However, we are seeing a high rate of response even on the screens they could click past.”
Dr. Ketterman and Dr. McPeak report no potential conflicts of interest.
TORONTO — , and, of course, it eliminated the work associated with managing paper records.
Due to the efficacy of the pre-visit capture, “all of the information — including individual responses and total scores — is available to the provider at a glance” by the time of the examination encounter, according to Brian T. Ketterman, MD, a third-year resident in pediatrics at the Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tennessee.
Urgent issues, such as suicidality risk, “are flagged so that they are seen first,” he added.
The goal of going paperless was to improve the amount and the consistency of data captured with each well visit, according to Dr. Ketterman. He described a major undertaking involving fundamental changes in the electronic medical record (EMR) system to accommodate the new approach.
Characterizing screening at well visits as “one of the most important jobs of a pediatrician” when he presented these data at the Pediatric Academic Societies annual meeting, he added that a paperless approach comes with many advantages.
Raising the Rate of Complete Data Capture
The American Academy of Pediatrics (AAP) has identified more than 30 screening elements at well-child visits. At his institution several additional screening elements have been added. Prior to going paperless, about 45.6% on average of this well-visit data was being captured in any specific patient encounter, even if the institution was doing well overall in capturing essential information, such as key laboratory values and immunizations.
The vast majority of the information that was missing depended on patient or family input, such as social determinants of health (SDoH), which includes the aspects of home environment, such as nutrition and safety. Dr. Ketterman said that going paperless was inspired by positive experiences reported elsewhere.
“We wanted to build on this work,” he said.
The goal of the program was to raise the rate of complete data capture at well visits to at least 80% and do this across all languages. The first step was to create digital forms in English and Spanish for completion unique to each milestone well-child visit defined by age. For those who speak English or Spanish, these forms were supplied through the patient portal several days before the visit.
For those who spoke one of the more than 40 other languages encountered among patients at Dr. Ketterman’s institution, an interpreter was supplied. If patients arrived at the clinic without completing the digital entry, they completed it on a tablet with the help of an interpreter if one was needed.
Prior to going paperless, all screening data were captured on paper forms completed in the waiting room. The provider then manually reviewed and scored the forms before they were then scanned into the medical records. The paperless approach has eliminated all of these steps and the information is already available for review by the time the pediatrician enters the examination room.
With more than 50,000 well-child checkups captured over a recent 15-month period of paperless questionnaires, the proportion with 100% data capture using what Dr. Ketterman characterized as “strict criteria” was 84%, surpassing the goal at the initiation of the program.
“We improved in almost every screening measure,” Dr. Ketterman said, providing P values that were mostly < .001 for a range of standard tests such as M-CHAT-R (Modified Checklist for Autism in Toddlers), QPA (Quick Parenting Assessment), and PSC-17 (Pediatric Symptom Checklist) when compared to the baseline period.
Additional Advantages
The improvement in well-visit data capture was the goal, but the list of other advantages of the paperless system is long. For one, the EMR system now automatically uses the data to offer guidance that might improve patient outcomes. For example, if the family reports that the child does not see a dentist or does not know how to swim, these lead prompt the EMR to provide resources, such as the names of dentists of swim programs, to address the problem.
As another example, screening questions that reveal food insecurity automatically trigger guidance for enrolling in the U.S. Department of Agriculture’s WIC (Women, Infants, and Children) food program. According to Dr. Ketterman, the proportion of children now enrolled in WIC has increased 10-fold from baseline. He also reported there was a twofold increase in the proportion of patients enrolled in a free book program as a result of a screening questions that ask about reading at home.
The improvement in well-visit data capture was seen across all languages. Even if the gains were not quite as good in languages other than English or Spanish, they were still highly significant relative to baseline.
A ‘Life-Changing’ Improvement
The discussion following his talk made it clear that similar approaches are being actively pursued nationwide. Several in the audience working on similar programs identified such challenges as getting electronic medical record (EMR) systems to cooperate, ensuring patient enrollment in the portals, and avoiding form completion fatigue, but the comments were uniformly supportive of the benefits of this approach.
“This has been life-changing for us,” said Katie E. McPeak, MD, a primary care pediatrician and Medical Director for Health Equity at the Children’s Hospital of Philadelphia. “The information is more accurate in the digital format and it reduces time for the clinician reviewing the data in the exam room.” She also agreed that paperless completion of screen captures better information on more topics, like sleep, nutrition, and mood disorders.
However, Dr. McPeak was one of those who was concerned about form fatigue. Patients have to enter extensive information over multiple screens for each well-child visit. She said this problem might need to be addressed if the success of paperless screening leads to even greater expansion of data requested.
In addressing the work behind creating a system of the depth and scope of the one he described, Dr. Ketterman acknowledged that it involved a daunting development process with substantial coding and testing. Referring to the EMR system used at his hospital, he said the preparation required an “epic guru,” but he said that input fatigue has not yet arisen as a major issue.
“Many of the screens are mandatory, so you cannot advance without completing them, but some are optional,” he noted. “However, we are seeing a high rate of response even on the screens they could click past.”
Dr. Ketterman and Dr. McPeak report no potential conflicts of interest.
FROM PAS 2024