Earlier this year, Representative Greg Murphy, MD, along with several cosponsors, introduced H.R. 7725, the Embracing Anti-Discrimination, Unbiased Curricula, and Advancing Truth in Education (EDUCATE) Act.

If enacted, the EDUCATE Act would cut off federal funding to medical schools that force students or faculty to adopt specific beliefs; discriminate based on race or ethnicity; or have diversity, equity, and inclusion (DEI) offices or any functional equivalent. The bill would also require accreditation agencies to check that their standards do not push these practices, while still allowing instruction about health issues tied to race or collecting data for research.

In response to the introduction of this act, CHEST published a statement in support of DEI practices and their necessary role within the practice of health care and medical training programs.

It is our belief that health care requires a solid patient-provider therapeutic alliance to achieve successful outcomes, and decades of scientific research have shown that a lack of clinician diversity worsens health disparities. For patients from historically underserved communities, having clinicians who share similar lived experiences almost always leads to significant improvements in patient outcomes. If identity concordance is not feasible, clinicians with considerable exposure to diverse patient populations, equitable approaches to care, and inclusive perspectives on health gained through continuing, comprehensive medical education and professional training can also positively impact outcomes.

Research indicates that a diverse medical workforce improves cultural competence and can help clinicians better meet the needs of patients from diverse backgrounds and ethnicities and that the benefits of diverse learning environments enhance the educational experience of all participants. Racial and ethnic health inequities illuminate the greatest gaps and worst patient outcomes, especially when compounded by disparities related to gender identity, ability, language, immigration status, sexual orientation, age, socioeconomics, and other social drivers of health. Research also shows that nearly one-fifth of Latine Americans avoid medical care due to concern about experiencing discrimination, Black Americans have significantly lower life expectancies, and Asian Americans are the only racial group to experience cancer as a leading cause of death. It is also well documented that communities experiencing disproportionately high rates of COVID-19 infection, hospitalization, and mortality when compared with White Americans include Black, Latine, Asian, Native Hawaiian, and Native Americans.

“In 2023, the CHEST organization shared its organizational values: community, inclusivity, innovation, advocacy, and integrity,” said CHEST President, Jack D. Buckley, MD, MPH, FCCP. “In strong accordance with these values and with our mission to champion the prevention, diagnosis, and treatment of chest diseases and advance the best patient outcomes, CHEST is firmly committed to the necessity of diversity, equity, and inclusion in health care research, education, and delivery.”

Guided by our core values, CHEST is relentlessly committed to improving the professional’s experience and patient outcomes equally. This commitment compels us to work toward eliminating disparities in the medical field. According to the most recent US Census projections, by 2045, White Americans will no longer be considered a racial majority, with Black, Latine, and Asian Americans continuing to rise. It is incumbent upon us to ensure that our clinician workforce reflects the diversity of its local and national communities.

The underrepresentation of physicians from racially diverse backgrounds is factually clear. Black physicians comprise 5% of the current physician workforce despite Black Americans representing 13% of the population.¹ Similarly, while Native Americans comprise 3% of the United States population, Native American physicians account for less than 1% of the physician workforce, with less than 10% of medical schools reporting total enrollment of more than four Native American students.² Where gender is concerned, women make up about 36% of the physician workforce, a professional disparity that is further exacerbated given the intersections of race and gender, resulting in a significant impact on the current workforce.³ Allowing disinformation to influence the future of medical education and patient care directly contradicts our mission as clinicians dedicated to improving the health of all people.

If physician representation and patient outcomes are linked, as research shows, the lack of diverse medical school representation has dire consequences for matriculation, job recruitment, retention, and promotion. Without supportive policies, programs, and equity-focused curriculums in medical education, we will never close the gap on professional disparities, which means we will similarly never close the gap on health disparities.

Our commitment to our members, all health care professionals, and the field of medicine means that we will stand firm in our defense of DEI today and every day until we have achieved optimal, equitable health for all people in all places. CHEST is committed to an intersectional approach to equitable health care education and delivery. We strive to design solutions that center the most impacted and radiate support outward, ensuring our interventions benefit all others experiencing discrimination.

Read more about CHEST’s commitment to diversity and other advocacy work on the CHEST website.

References

1. AAMC. Figure 18. Percentage of all active physicians by race/ethnicity, 2018. AAMC; 2019. https://www.aamc.org/data-reports/workforce/data/figure-18-percentage-all-active-physicians-race/ethnicity-2018#:~:text=Diversity%20in%20Medicine%3A%20Facts%20and%20Figures%202019,-Diversity%20in%20Medicine&text=Among%20active%20physicians%2C%2056.2%25%20identified,as%20Black%20or%20African%20American

2. Murphy B. New effort to help Native American pre-meds pursue physician dreams. AMA. January 13, 2022. https://www.ama-assn.org/education/medical-school-diversity/new-effort-help-native-american-pre-meds-pursue-physician-dreams

3. AAMC. U.S. Physician Workforce Data Dashboard. AAMC; 2023. https://www.aamc.org/data-reports/report/us-physician-workforce-data-dashboard

Earlier this year, Representative Greg Murphy, MD, along with several cosponsors, introduced H.R. 7725, the Embracing Anti-Discrimination, Unbiased Curricula, and Advancing Truth in Education (EDUCATE) Act.

If enacted, the EDUCATE Act would cut off federal funding to medical schools that force students or faculty to adopt specific beliefs; discriminate based on race or ethnicity; or have diversity, equity, and inclusion (DEI) offices or any functional equivalent. The bill would also require accreditation agencies to check that their standards do not push these practices, while still allowing instruction about health issues tied to race or collecting data for research.

In response to the introduction of this act, CHEST published a statement in support of DEI practices and their necessary role within the practice of health care and medical training programs.

It is our belief that health care requires a solid patient-provider therapeutic alliance to achieve successful outcomes, and decades of scientific research have shown that a lack of clinician diversity worsens health disparities. For patients from historically underserved communities, having clinicians who share similar lived experiences almost always leads to significant improvements in patient outcomes. If identity concordance is not feasible, clinicians with considerable exposure to diverse patient populations, equitable approaches to care, and inclusive perspectives on health gained through continuing, comprehensive medical education and professional training can also positively impact outcomes.

Research indicates that a diverse medical workforce improves cultural competence and can help clinicians better meet the needs of patients from diverse backgrounds and ethnicities and that the benefits of diverse learning environments enhance the educational experience of all participants. Racial and ethnic health inequities illuminate the greatest gaps and worst patient outcomes, especially when compounded by disparities related to gender identity, ability, language, immigration status, sexual orientation, age, socioeconomics, and other social drivers of health. Research also shows that nearly one-fifth of Latine Americans avoid medical care due to concern about experiencing discrimination, Black Americans have significantly lower life expectancies, and Asian Americans are the only racial group to experience cancer as a leading cause of death. It is also well documented that communities experiencing disproportionately high rates of COVID-19 infection, hospitalization, and mortality when compared with White Americans include Black, Latine, Asian, Native Hawaiian, and Native Americans.

“In 2023, the CHEST organization shared its organizational values: community, inclusivity, innovation, advocacy, and integrity,” said CHEST President, Jack D. Buckley, MD, MPH, FCCP. “In strong accordance with these values and with our mission to champion the prevention, diagnosis, and treatment of chest diseases and advance the best patient outcomes, CHEST is firmly committed to the necessity of diversity, equity, and inclusion in health care research, education, and delivery.”

Guided by our core values, CHEST is relentlessly committed to improving the professional’s experience and patient outcomes equally. This commitment compels us to work toward eliminating disparities in the medical field. According to the most recent US Census projections, by 2045, White Americans will no longer be considered a racial majority, with Black, Latine, and Asian Americans continuing to rise. It is incumbent upon us to ensure that our clinician workforce reflects the diversity of its local and national communities.

The underrepresentation of physicians from racially diverse backgrounds is factually clear. Black physicians comprise 5% of the current physician workforce despite Black Americans representing 13% of the population.¹ Similarly, while Native Americans comprise 3% of the United States population, Native American physicians account for less than 1% of the physician workforce, with less than 10% of medical schools reporting total enrollment of more than four Native American students.² Where gender is concerned, women make up about 36% of the physician workforce, a professional disparity that is further exacerbated given the intersections of race and gender, resulting in a significant impact on the current workforce.³ Allowing disinformation to influence the future of medical education and patient care directly contradicts our mission as clinicians dedicated to improving the health of all people.

If physician representation and patient outcomes are linked, as research shows, the lack of diverse medical school representation has dire consequences for matriculation, job recruitment, retention, and promotion. Without supportive policies, programs, and equity-focused curriculums in medical education, we will never close the gap on professional disparities, which means we will similarly never close the gap on health disparities.

Our commitment to our members, all health care professionals, and the field of medicine means that we will stand firm in our defense of DEI today and every day until we have achieved optimal, equitable health for all people in all places. CHEST is committed to an intersectional approach to equitable health care education and delivery. We strive to design solutions that center the most impacted and radiate support outward, ensuring our interventions benefit all others experiencing discrimination.

Read more about CHEST’s commitment to diversity and other advocacy work on the CHEST website.

References

1. AAMC. Figure 18. Percentage of all active physicians by race/ethnicity, 2018. AAMC; 2019. https://www.aamc.org/data-reports/workforce/data/figure-18-percentage-all-active-physicians-race/ethnicity-2018#:~:text=Diversity%20in%20Medicine%3A%20Facts%20and%20Figures%202019,-Diversity%20in%20Medicine&text=Among%20active%20physicians%2C%2056.2%25%20identified,as%20Black%20or%20African%20American

2. Murphy B. New effort to help Native American pre-meds pursue physician dreams. AMA. January 13, 2022. https://www.ama-assn.org/education/medical-school-diversity/new-effort-help-native-american-pre-meds-pursue-physician-dreams

3. AAMC. U.S. Physician Workforce Data Dashboard. AAMC; 2023. https://www.aamc.org/data-reports/report/us-physician-workforce-data-dashboard

Earlier this year, Representative Greg Murphy, MD, along with several cosponsors, introduced H.R. 7725, the Embracing Anti-Discrimination, Unbiased Curricula, and Advancing Truth in Education (EDUCATE) Act.

If enacted, the EDUCATE Act would cut off federal funding to medical schools that force students or faculty to adopt specific beliefs; discriminate based on race or ethnicity; or have diversity, equity, and inclusion (DEI) offices or any functional equivalent. The bill would also require accreditation agencies to check that their standards do not push these practices, while still allowing instruction about health issues tied to race or collecting data for research.

In response to the introduction of this act, CHEST published a statement in support of DEI practices and their necessary role within the practice of health care and medical training programs.

It is our belief that health care requires a solid patient-provider therapeutic alliance to achieve successful outcomes, and decades of scientific research have shown that a lack of clinician diversity worsens health disparities. For patients from historically underserved communities, having clinicians who share similar lived experiences almost always leads to significant improvements in patient outcomes. If identity concordance is not feasible, clinicians with considerable exposure to diverse patient populations, equitable approaches to care, and inclusive perspectives on health gained through continuing, comprehensive medical education and professional training can also positively impact outcomes.

Research indicates that a diverse medical workforce improves cultural competence and can help clinicians better meet the needs of patients from diverse backgrounds and ethnicities and that the benefits of diverse learning environments enhance the educational experience of all participants. Racial and ethnic health inequities illuminate the greatest gaps and worst patient outcomes, especially when compounded by disparities related to gender identity, ability, language, immigration status, sexual orientation, age, socioeconomics, and other social drivers of health. Research also shows that nearly one-fifth of Latine Americans avoid medical care due to concern about experiencing discrimination, Black Americans have significantly lower life expectancies, and Asian Americans are the only racial group to experience cancer as a leading cause of death. It is also well documented that communities experiencing disproportionately high rates of COVID-19 infection, hospitalization, and mortality when compared with White Americans include Black, Latine, Asian, Native Hawaiian, and Native Americans.

“In 2023, the CHEST organization shared its organizational values: community, inclusivity, innovation, advocacy, and integrity,” said CHEST President, Jack D. Buckley, MD, MPH, FCCP. “In strong accordance with these values and with our mission to champion the prevention, diagnosis, and treatment of chest diseases and advance the best patient outcomes, CHEST is firmly committed to the necessity of diversity, equity, and inclusion in health care research, education, and delivery.”

Guided by our core values, CHEST is relentlessly committed to improving the professional’s experience and patient outcomes equally. This commitment compels us to work toward eliminating disparities in the medical field. According to the most recent US Census projections, by 2045, White Americans will no longer be considered a racial majority, with Black, Latine, and Asian Americans continuing to rise. It is incumbent upon us to ensure that our clinician workforce reflects the diversity of its local and national communities.

The underrepresentation of physicians from racially diverse backgrounds is factually clear. Black physicians comprise 5% of the current physician workforce despite Black Americans representing 13% of the population.¹ Similarly, while Native Americans comprise 3% of the United States population, Native American physicians account for less than 1% of the physician workforce, with less than 10% of medical schools reporting total enrollment of more than four Native American students.² Where gender is concerned, women make up about 36% of the physician workforce, a professional disparity that is further exacerbated given the intersections of race and gender, resulting in a significant impact on the current workforce.³ Allowing disinformation to influence the future of medical education and patient care directly contradicts our mission as clinicians dedicated to improving the health of all people.

If physician representation and patient outcomes are linked, as research shows, the lack of diverse medical school representation has dire consequences for matriculation, job recruitment, retention, and promotion. Without supportive policies, programs, and equity-focused curriculums in medical education, we will never close the gap on professional disparities, which means we will similarly never close the gap on health disparities.

Our commitment to our members, all health care professionals, and the field of medicine means that we will stand firm in our defense of DEI today and every day until we have achieved optimal, equitable health for all people in all places. CHEST is committed to an intersectional approach to equitable health care education and delivery. We strive to design solutions that center the most impacted and radiate support outward, ensuring our interventions benefit all others experiencing discrimination.

Read more about CHEST’s commitment to diversity and other advocacy work on the CHEST website.

References

1. AAMC. Figure 18. Percentage of all active physicians by race/ethnicity, 2018. AAMC; 2019. https://www.aamc.org/data-reports/workforce/data/figure-18-percentage-all-active-physicians-race/ethnicity-2018#:~:text=Diversity%20in%20Medicine%3A%20Facts%20and%20Figures%202019,-Diversity%20in%20Medicine&text=Among%20active%20physicians%2C%2056.2%25%20identified,as%20Black%20or%20African%20American

2. Murphy B. New effort to help Native American pre-meds pursue physician dreams. AMA. January 13, 2022. https://www.ama-assn.org/education/medical-school-diversity/new-effort-help-native-american-pre-meds-pursue-physician-dreams

3. AAMC. U.S. Physician Workforce Data Dashboard. AAMC; 2023. https://www.aamc.org/data-reports/report/us-physician-workforce-data-dashboard

Pseudomonas aeruginosa is a clinically important organism that infects patients with noncystic fibrosis bronchiectasis (NCFB). In the United States, the estimated prevalence of NCFB is 213 per 100,000 across all age groups and 813 per 100,000 in the over 65 age group.¹ A retrospective cohort study suggests the incidence of NCFB as ascertained from International Classification of Diseases codes may significantly underestimate its true prevalence.²

As the incidence of patients with NCFB continues to increase, the impact of the Pseudomonas infection is expected to grow. A recent retrospective cohort study of commercial claims from IQVIA’s PharMetrics Plus database for the period 2006 to 2020 showed that patients with NCFB and Pseudomonas infection had on average 2.58 hospital admissions per year, with a mean length of stay of 9.94 (± 11.06) days, compared with 1.18 admissions per year, with a mean length of stay of 6.5 (± 8.42) days, in patients with Pseudomonas-negative NCFB. The same trend applied to 30-day readmissions and ICU admissions, 1.32 (± 2.51 days) vs 0.47 (± 1.30 days) and 0.95 (± 1.62 days) vs 0.33 (± 0.76 days), respectively. The differential cost of care per patient per year between patients with NCFB with and without Pseudomonas infection ranged from $55,225 to $315,901.³

CHEST

Recent data from the United States Bronchiectasis Registry showed the probability of acquiring Pseudomonas aeruginosa was 3% annually.⁴ The prevalence of Pseudomonas infection in a large, geographically diverse cohort in the United States was quoted at 15%.⁵ A retrospective analysis of the European Bronchiectasis Registry database showed Pseudomonas infection was the most commonly isolated pathogen (21.8%).⁶

Given the high incidence and prevalence of NCFB, the high prevalence of Pseudomonas infection in patients with NCFB, and the associated costs and morbidity from infection, identifying effective treatments has become a priority. The British, Spanish (SEPAR), South African, and European bronchiectasis guidelines outline several antibiotic regimens meant to achieve eradication. Generally, there is induction with a (1) quinolone, (2) β-lactam + aminoglycoside, or (3) quinolone with an inhaled antibiotic followed by three months of maintenance inhaled antibiotics.^7-10 SEPAR allows for retreatment for recurrence at any time during the first year with any regimen.

For chronic Pseudomonas infection, SEPAR recommends treatment with inhaled antibiotics for patients with more than two exacerbations or one hospitalization, while the threshold in the British and European guidelines is more than three exacerbations. Azithromycin may be used for those who are intolerant or allergic to the nebulized antibiotics. It is worth noting that in the United States, the antibiotics colistin, ciprofloxacin, aztreonam, gentamicin, and tobramycin are administered off label for this indication. A systematic review found a 10% rate of bronchospasm in the treated group compared with 2.3% in the control group, and premedication with albuterol is often needed.¹¹

Unfortunately, the data supporting the listed eradication and suppressive regimens are weak. A systematic review and meta-analysis of six observational studies including 289 patients showed a 12-month eradication rate of only 40% (95% CI, 34-45; P < 0.00001; I² = 0).¹² These results are disappointing and identify a need for further research into the manner in which Pseudomonas infection interacts with the host lung.

We currently know Pseudomonas infection evades antibiotics and host defenses by accumulating mutations and deletions. These include loss-of-function mutations in mucA (mucoidy), lasR (quorum-sensing), mexS (regulates the antibiotic efflux pump), and other genes related to the production of the polysaccharides Psl and Pel (which contribute to biofilm formation).¹³ There may also be differences in low and high bacteria microbial networks that interact differently with host cytokines to create an unstable environment that predisposes to exacerbation.¹⁴

In an attempt to improve our eradication and suppression rates, investigators have begun to target specific aspects of Pseudomonas infection behavior. The GREAT-2 trial compares gremubamab (a bivalent, bispecific, monoclonal antibody targeting Psl exopolysaccharide and the type 3 secretion system component of PcrV) with placebo in patients with chronic Pseudomonas infection. A phase II trial with the phosphodiesterase inhibitor esifentrine, a phase III trial with a reversible DPP1 inhibitor called brensocatib (ASPEN), and a phase II trial with the CatC inhibitor BI 1291583 (Airleaf) are also being conducted. Each of these agents targets mediators of neutrophil inflammation.

In summary, NCFB with Pseudomonas infection is common and leads to an increase in costs, respiratory exacerbations, and hospitalizations. While eradication and suppression are recommended, they are difficult to achieve and require sustained durations of expensive medications that can be difficult to tolerate. Antibiotic therapies will continue to be studied (the ERASE randomized controlled trial to investigate the efficacy and safety of tobramycin to eradicate Pseudomonas infection is currently underway), but targeted therapies represent a promising new approach to combating this stubbornly resistant bacteria. The NCFB community will be watching closely to see whether medicines targeting molecular behavior and host interaction can achieve what antibiotic regimens thus far have not: consistent and sustainable eradication.
 

Dr. Green is Assistant Professor in Medicine, Medical Director, Bronchiectasis Program, UMass Chan/Baystate Health, Chest Infections Section, Member-at-Large

References

1. Weycker D, Hansen GL, Seifer FD. Prevalence and incidence of noncystic fibrosis bronchiectasis among US adults in 2013. Chron Respir Dis. 2017;14(4):377-384. doi: 10.1177/1479972317709649

2. Green O, Liautaud S, Knee A, Modahl L. Measuring accuracy of International Classification of Diseases codes in identification of patients with non-cystic fibrosis bronchiectasis. ERJ Open Res. 2024;10(2):00715-2023. doi: 10.1183/23120541.00715-2023

3. Franklin M, Minshall ME, Pontenani F, Devarajan S. Impact of Pseudomonas aeruginosa on resource utilization and costs in patients with exacerbated non-cystic fibrosis bronchiectasis. J Med Econ. 2024;27(1):671-677. doi: 10.1080/13696998.2024.2340382

4. Aksamit TR, Locantore N, Addrizzo-Harris D, et al. Five-year outcomes among U.S. bronchiectasis and NTM research registry patients. Am J Respir Crit Care Med. Accepted manuscript. Published online April 26, 2024.

5. Dean SG, Blakney RA, Ricotta EE, et al. Bronchiectasis-associated infections and outcomes in a large, geographically diverse electronic health record cohort in the United States. BMC Pulm Med. 2024;24(1):172. doi: 10.1186/s12890-024-02973-3

6. Chalmers JD, Polverino E, Crichton ML, et al. Bronchiectasis in Europe: data on disease characteristics from the European Bronchiectasis registry (EMBARC). Lancet Respir Med. 2023;11(7):637-649. doi: 10.1016/S2213-2600(23)00093-0

7. Polverino E, Goeminne PC, McDonnell MJ, et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017;50(3):1700629. doi: 10.1183/13993003.00629-2017

8. Martínez-García MÁ, Máiz L, Olveira C, et al. Spanish guidelines on treatment of bronchiectasis in adults. Arch Bronconeumol. 2018;54(2):88-98. doi: 10.1016/j.arbres.2017.07.016

9. Hill AT, Sullivan AL, Chalmers JD, et al. British Thoracic Society guideline for bronchiectasis in adults. Thorax. 2019;74(Suppl 1):1-69. doi: 10.1136/thoraxjnl-2018-212463

10. Goolam Mahomed A, Maasdorp SD, Barnes R, et al. South African Thoracic Society position statement on the management of non-cystic fibrosis bronchiectasis in adults: 2023. Afr J Thorac Crit Care Med. 2023;29(2):10.7196/AJTCCM. 2023.v29i2.647. doi: 10.7196/AJTCCM.2023.v29i2.647

11. Brodt AM, Stovold E, Zhang L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic review. Eur Respir J. 2014;44(2):382-393. doi: 10.1183/09031936.00018414

12. Conceição M, Shteinberg M, Goeminne P, Altenburg J, Chalmers JD. Eradication treatment for Pseudomonas aeruginosa infection in adults with bronchiectasis: a systematic review and meta-analysis. Eur Respir Rev. 2024;33(171):230178. doi: 10.1183/16000617.0178-2023

13. Hilliam Y, Moore MP, Lamont IL, et al. Pseudomonas aeruginosa adaptation and diversification in the non-cystic fibrosis bronchiectasis lung. Eur Respir J. 2017;49(4):1602108. doi: 10.1183/13993003.02108-2016

14. Gramegna A, Kumar Narayana J, Amati F, et al. Microbial inflammatory networks in bronchiectasis exacerbators with Pseudomonas aeruginosa. Chest. 2023;164(1):65-68. doi: 10.1016/j.chest.2023.02.014

Pseudomonas aeruginosa is a clinically important organism that infects patients with noncystic fibrosis bronchiectasis (NCFB). In the United States, the estimated prevalence of NCFB is 213 per 100,000 across all age groups and 813 per 100,000 in the over 65 age group.¹ A retrospective cohort study suggests the incidence of NCFB as ascertained from International Classification of Diseases codes may significantly underestimate its true prevalence.²

As the incidence of patients with NCFB continues to increase, the impact of the Pseudomonas infection is expected to grow. A recent retrospective cohort study of commercial claims from IQVIA’s PharMetrics Plus database for the period 2006 to 2020 showed that patients with NCFB and Pseudomonas infection had on average 2.58 hospital admissions per year, with a mean length of stay of 9.94 (± 11.06) days, compared with 1.18 admissions per year, with a mean length of stay of 6.5 (± 8.42) days, in patients with Pseudomonas-negative NCFB. The same trend applied to 30-day readmissions and ICU admissions, 1.32 (± 2.51 days) vs 0.47 (± 1.30 days) and 0.95 (± 1.62 days) vs 0.33 (± 0.76 days), respectively. The differential cost of care per patient per year between patients with NCFB with and without Pseudomonas infection ranged from $55,225 to $315,901.³

CHEST

Recent data from the United States Bronchiectasis Registry showed the probability of acquiring Pseudomonas aeruginosa was 3% annually.⁴ The prevalence of Pseudomonas infection in a large, geographically diverse cohort in the United States was quoted at 15%.⁵ A retrospective analysis of the European Bronchiectasis Registry database showed Pseudomonas infection was the most commonly isolated pathogen (21.8%).⁶

Given the high incidence and prevalence of NCFB, the high prevalence of Pseudomonas infection in patients with NCFB, and the associated costs and morbidity from infection, identifying effective treatments has become a priority. The British, Spanish (SEPAR), South African, and European bronchiectasis guidelines outline several antibiotic regimens meant to achieve eradication. Generally, there is induction with a (1) quinolone, (2) β-lactam + aminoglycoside, or (3) quinolone with an inhaled antibiotic followed by three months of maintenance inhaled antibiotics.^7-10 SEPAR allows for retreatment for recurrence at any time during the first year with any regimen.

For chronic Pseudomonas infection, SEPAR recommends treatment with inhaled antibiotics for patients with more than two exacerbations or one hospitalization, while the threshold in the British and European guidelines is more than three exacerbations. Azithromycin may be used for those who are intolerant or allergic to the nebulized antibiotics. It is worth noting that in the United States, the antibiotics colistin, ciprofloxacin, aztreonam, gentamicin, and tobramycin are administered off label for this indication. A systematic review found a 10% rate of bronchospasm in the treated group compared with 2.3% in the control group, and premedication with albuterol is often needed.¹¹

Unfortunately, the data supporting the listed eradication and suppressive regimens are weak. A systematic review and meta-analysis of six observational studies including 289 patients showed a 12-month eradication rate of only 40% (95% CI, 34-45; P < 0.00001; I² = 0).¹² These results are disappointing and identify a need for further research into the manner in which Pseudomonas infection interacts with the host lung.

We currently know Pseudomonas infection evades antibiotics and host defenses by accumulating mutations and deletions. These include loss-of-function mutations in mucA (mucoidy), lasR (quorum-sensing), mexS (regulates the antibiotic efflux pump), and other genes related to the production of the polysaccharides Psl and Pel (which contribute to biofilm formation).¹³ There may also be differences in low and high bacteria microbial networks that interact differently with host cytokines to create an unstable environment that predisposes to exacerbation.¹⁴

In an attempt to improve our eradication and suppression rates, investigators have begun to target specific aspects of Pseudomonas infection behavior. The GREAT-2 trial compares gremubamab (a bivalent, bispecific, monoclonal antibody targeting Psl exopolysaccharide and the type 3 secretion system component of PcrV) with placebo in patients with chronic Pseudomonas infection. A phase II trial with the phosphodiesterase inhibitor esifentrine, a phase III trial with a reversible DPP1 inhibitor called brensocatib (ASPEN), and a phase II trial with the CatC inhibitor BI 1291583 (Airleaf) are also being conducted. Each of these agents targets mediators of neutrophil inflammation.

In summary, NCFB with Pseudomonas infection is common and leads to an increase in costs, respiratory exacerbations, and hospitalizations. While eradication and suppression are recommended, they are difficult to achieve and require sustained durations of expensive medications that can be difficult to tolerate. Antibiotic therapies will continue to be studied (the ERASE randomized controlled trial to investigate the efficacy and safety of tobramycin to eradicate Pseudomonas infection is currently underway), but targeted therapies represent a promising new approach to combating this stubbornly resistant bacteria. The NCFB community will be watching closely to see whether medicines targeting molecular behavior and host interaction can achieve what antibiotic regimens thus far have not: consistent and sustainable eradication.
 

Dr. Green is Assistant Professor in Medicine, Medical Director, Bronchiectasis Program, UMass Chan/Baystate Health, Chest Infections Section, Member-at-Large

References

1. Weycker D, Hansen GL, Seifer FD. Prevalence and incidence of noncystic fibrosis bronchiectasis among US adults in 2013. Chron Respir Dis. 2017;14(4):377-384. doi: 10.1177/1479972317709649

2. Green O, Liautaud S, Knee A, Modahl L. Measuring accuracy of International Classification of Diseases codes in identification of patients with non-cystic fibrosis bronchiectasis. ERJ Open Res. 2024;10(2):00715-2023. doi: 10.1183/23120541.00715-2023

3. Franklin M, Minshall ME, Pontenani F, Devarajan S. Impact of Pseudomonas aeruginosa on resource utilization and costs in patients with exacerbated non-cystic fibrosis bronchiectasis. J Med Econ. 2024;27(1):671-677. doi: 10.1080/13696998.2024.2340382

4. Aksamit TR, Locantore N, Addrizzo-Harris D, et al. Five-year outcomes among U.S. bronchiectasis and NTM research registry patients. Am J Respir Crit Care Med. Accepted manuscript. Published online April 26, 2024.

5. Dean SG, Blakney RA, Ricotta EE, et al. Bronchiectasis-associated infections and outcomes in a large, geographically diverse electronic health record cohort in the United States. BMC Pulm Med. 2024;24(1):172. doi: 10.1186/s12890-024-02973-3

6. Chalmers JD, Polverino E, Crichton ML, et al. Bronchiectasis in Europe: data on disease characteristics from the European Bronchiectasis registry (EMBARC). Lancet Respir Med. 2023;11(7):637-649. doi: 10.1016/S2213-2600(23)00093-0

7. Polverino E, Goeminne PC, McDonnell MJ, et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017;50(3):1700629. doi: 10.1183/13993003.00629-2017

8. Martínez-García MÁ, Máiz L, Olveira C, et al. Spanish guidelines on treatment of bronchiectasis in adults. Arch Bronconeumol. 2018;54(2):88-98. doi: 10.1016/j.arbres.2017.07.016

9. Hill AT, Sullivan AL, Chalmers JD, et al. British Thoracic Society guideline for bronchiectasis in adults. Thorax. 2019;74(Suppl 1):1-69. doi: 10.1136/thoraxjnl-2018-212463

10. Goolam Mahomed A, Maasdorp SD, Barnes R, et al. South African Thoracic Society position statement on the management of non-cystic fibrosis bronchiectasis in adults: 2023. Afr J Thorac Crit Care Med. 2023;29(2):10.7196/AJTCCM. 2023.v29i2.647. doi: 10.7196/AJTCCM.2023.v29i2.647

11. Brodt AM, Stovold E, Zhang L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic review. Eur Respir J. 2014;44(2):382-393. doi: 10.1183/09031936.00018414

12. Conceição M, Shteinberg M, Goeminne P, Altenburg J, Chalmers JD. Eradication treatment for Pseudomonas aeruginosa infection in adults with bronchiectasis: a systematic review and meta-analysis. Eur Respir Rev. 2024;33(171):230178. doi: 10.1183/16000617.0178-2023

13. Hilliam Y, Moore MP, Lamont IL, et al. Pseudomonas aeruginosa adaptation and diversification in the non-cystic fibrosis bronchiectasis lung. Eur Respir J. 2017;49(4):1602108. doi: 10.1183/13993003.02108-2016

14. Gramegna A, Kumar Narayana J, Amati F, et al. Microbial inflammatory networks in bronchiectasis exacerbators with Pseudomonas aeruginosa. Chest. 2023;164(1):65-68. doi: 10.1016/j.chest.2023.02.014

Pseudomonas aeruginosa is a clinically important organism that infects patients with noncystic fibrosis bronchiectasis (NCFB). In the United States, the estimated prevalence of NCFB is 213 per 100,000 across all age groups and 813 per 100,000 in the over 65 age group.¹ A retrospective cohort study suggests the incidence of NCFB as ascertained from International Classification of Diseases codes may significantly underestimate its true prevalence.²

As the incidence of patients with NCFB continues to increase, the impact of the Pseudomonas infection is expected to grow. A recent retrospective cohort study of commercial claims from IQVIA’s PharMetrics Plus database for the period 2006 to 2020 showed that patients with NCFB and Pseudomonas infection had on average 2.58 hospital admissions per year, with a mean length of stay of 9.94 (± 11.06) days, compared with 1.18 admissions per year, with a mean length of stay of 6.5 (± 8.42) days, in patients with Pseudomonas-negative NCFB. The same trend applied to 30-day readmissions and ICU admissions, 1.32 (± 2.51 days) vs 0.47 (± 1.30 days) and 0.95 (± 1.62 days) vs 0.33 (± 0.76 days), respectively. The differential cost of care per patient per year between patients with NCFB with and without Pseudomonas infection ranged from $55,225 to $315,901.³

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Recent data from the United States Bronchiectasis Registry showed the probability of acquiring Pseudomonas aeruginosa was 3% annually.⁴ The prevalence of Pseudomonas infection in a large, geographically diverse cohort in the United States was quoted at 15%.⁵ A retrospective analysis of the European Bronchiectasis Registry database showed Pseudomonas infection was the most commonly isolated pathogen (21.8%).⁶

Given the high incidence and prevalence of NCFB, the high prevalence of Pseudomonas infection in patients with NCFB, and the associated costs and morbidity from infection, identifying effective treatments has become a priority. The British, Spanish (SEPAR), South African, and European bronchiectasis guidelines outline several antibiotic regimens meant to achieve eradication. Generally, there is induction with a (1) quinolone, (2) β-lactam + aminoglycoside, or (3) quinolone with an inhaled antibiotic followed by three months of maintenance inhaled antibiotics.^7-10 SEPAR allows for retreatment for recurrence at any time during the first year with any regimen.

For chronic Pseudomonas infection, SEPAR recommends treatment with inhaled antibiotics for patients with more than two exacerbations or one hospitalization, while the threshold in the British and European guidelines is more than three exacerbations. Azithromycin may be used for those who are intolerant or allergic to the nebulized antibiotics. It is worth noting that in the United States, the antibiotics colistin, ciprofloxacin, aztreonam, gentamicin, and tobramycin are administered off label for this indication. A systematic review found a 10% rate of bronchospasm in the treated group compared with 2.3% in the control group, and premedication with albuterol is often needed.¹¹

Unfortunately, the data supporting the listed eradication and suppressive regimens are weak. A systematic review and meta-analysis of six observational studies including 289 patients showed a 12-month eradication rate of only 40% (95% CI, 34-45; P < 0.00001; I² = 0).¹² These results are disappointing and identify a need for further research into the manner in which Pseudomonas infection interacts with the host lung.

We currently know Pseudomonas infection evades antibiotics and host defenses by accumulating mutations and deletions. These include loss-of-function mutations in mucA (mucoidy), lasR (quorum-sensing), mexS (regulates the antibiotic efflux pump), and other genes related to the production of the polysaccharides Psl and Pel (which contribute to biofilm formation).¹³ There may also be differences in low and high bacteria microbial networks that interact differently with host cytokines to create an unstable environment that predisposes to exacerbation.¹⁴

In an attempt to improve our eradication and suppression rates, investigators have begun to target specific aspects of Pseudomonas infection behavior. The GREAT-2 trial compares gremubamab (a bivalent, bispecific, monoclonal antibody targeting Psl exopolysaccharide and the type 3 secretion system component of PcrV) with placebo in patients with chronic Pseudomonas infection. A phase II trial with the phosphodiesterase inhibitor esifentrine, a phase III trial with a reversible DPP1 inhibitor called brensocatib (ASPEN), and a phase II trial with the CatC inhibitor BI 1291583 (Airleaf) are also being conducted. Each of these agents targets mediators of neutrophil inflammation.

In summary, NCFB with Pseudomonas infection is common and leads to an increase in costs, respiratory exacerbations, and hospitalizations. While eradication and suppression are recommended, they are difficult to achieve and require sustained durations of expensive medications that can be difficult to tolerate. Antibiotic therapies will continue to be studied (the ERASE randomized controlled trial to investigate the efficacy and safety of tobramycin to eradicate Pseudomonas infection is currently underway), but targeted therapies represent a promising new approach to combating this stubbornly resistant bacteria. The NCFB community will be watching closely to see whether medicines targeting molecular behavior and host interaction can achieve what antibiotic regimens thus far have not: consistent and sustainable eradication.
 

Dr. Green is Assistant Professor in Medicine, Medical Director, Bronchiectasis Program, UMass Chan/Baystate Health, Chest Infections Section, Member-at-Large

References

1. Weycker D, Hansen GL, Seifer FD. Prevalence and incidence of noncystic fibrosis bronchiectasis among US adults in 2013. Chron Respir Dis. 2017;14(4):377-384. doi: 10.1177/1479972317709649

2. Green O, Liautaud S, Knee A, Modahl L. Measuring accuracy of International Classification of Diseases codes in identification of patients with non-cystic fibrosis bronchiectasis. ERJ Open Res. 2024;10(2):00715-2023. doi: 10.1183/23120541.00715-2023

3. Franklin M, Minshall ME, Pontenani F, Devarajan S. Impact of Pseudomonas aeruginosa on resource utilization and costs in patients with exacerbated non-cystic fibrosis bronchiectasis. J Med Econ. 2024;27(1):671-677. doi: 10.1080/13696998.2024.2340382

4. Aksamit TR, Locantore N, Addrizzo-Harris D, et al. Five-year outcomes among U.S. bronchiectasis and NTM research registry patients. Am J Respir Crit Care Med. Accepted manuscript. Published online April 26, 2024.

5. Dean SG, Blakney RA, Ricotta EE, et al. Bronchiectasis-associated infections and outcomes in a large, geographically diverse electronic health record cohort in the United States. BMC Pulm Med. 2024;24(1):172. doi: 10.1186/s12890-024-02973-3

6. Chalmers JD, Polverino E, Crichton ML, et al. Bronchiectasis in Europe: data on disease characteristics from the European Bronchiectasis registry (EMBARC). Lancet Respir Med. 2023;11(7):637-649. doi: 10.1016/S2213-2600(23)00093-0

7. Polverino E, Goeminne PC, McDonnell MJ, et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017;50(3):1700629. doi: 10.1183/13993003.00629-2017

8. Martínez-García MÁ, Máiz L, Olveira C, et al. Spanish guidelines on treatment of bronchiectasis in adults. Arch Bronconeumol. 2018;54(2):88-98. doi: 10.1016/j.arbres.2017.07.016

9. Hill AT, Sullivan AL, Chalmers JD, et al. British Thoracic Society guideline for bronchiectasis in adults. Thorax. 2019;74(Suppl 1):1-69. doi: 10.1136/thoraxjnl-2018-212463

10. Goolam Mahomed A, Maasdorp SD, Barnes R, et al. South African Thoracic Society position statement on the management of non-cystic fibrosis bronchiectasis in adults: 2023. Afr J Thorac Crit Care Med. 2023;29(2):10.7196/AJTCCM. 2023.v29i2.647. doi: 10.7196/AJTCCM.2023.v29i2.647

11. Brodt AM, Stovold E, Zhang L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic review. Eur Respir J. 2014;44(2):382-393. doi: 10.1183/09031936.00018414

12. Conceição M, Shteinberg M, Goeminne P, Altenburg J, Chalmers JD. Eradication treatment for Pseudomonas aeruginosa infection in adults with bronchiectasis: a systematic review and meta-analysis. Eur Respir Rev. 2024;33(171):230178. doi: 10.1183/16000617.0178-2023

13. Hilliam Y, Moore MP, Lamont IL, et al. Pseudomonas aeruginosa adaptation and diversification in the non-cystic fibrosis bronchiectasis lung. Eur Respir J. 2017;49(4):1602108. doi: 10.1183/13993003.02108-2016

14. Gramegna A, Kumar Narayana J, Amati F, et al. Microbial inflammatory networks in bronchiectasis exacerbators with Pseudomonas aeruginosa. Chest. 2023;164(1):65-68. doi: 10.1016/j.chest.2023.02.014

Sleep Medicine Network

Respiratory-Related Sleep Disorders Section

Considering the recent Olympics, it is timely to review the importance of sleep for optimal athletic performance. When surveyed, 20% to 50% of athletes report poor or insufficient sleep, with consequences across four categories.^1,2

Athletic performance: Objective measures of athletic performance, such as oxygen-carrying capacity during cardiopulmonary exercise and even sport-specific accuracy measures, like shooting percentage in basketball, have been shown to worsen with decreased sleep.

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References

1. Cook JD, Charest J. Sleep and performance in professional athletes. Curr Sleep Med Rep. 2023;9(1):56-81.



2. Charest J, Grandner MA. Sleep and athletic performance: impacts on physical performance, mental performance, injury risk and recovery, and mental health. Sleep Med Clin. 2020;15(1):41-57.

Sleep Medicine Network

Respiratory-Related Sleep Disorders Section

Considering the recent Olympics, it is timely to review the importance of sleep for optimal athletic performance. When surveyed, 20% to 50% of athletes report poor or insufficient sleep, with consequences across four categories.^1,2

Athletic performance: Objective measures of athletic performance, such as oxygen-carrying capacity during cardiopulmonary exercise and even sport-specific accuracy measures, like shooting percentage in basketball, have been shown to worsen with decreased sleep.

CHEST

CHEST

References

1. Cook JD, Charest J. Sleep and performance in professional athletes. Curr Sleep Med Rep. 2023;9(1):56-81.



2. Charest J, Grandner MA. Sleep and athletic performance: impacts on physical performance, mental performance, injury risk and recovery, and mental health. Sleep Med Clin. 2020;15(1):41-57.

Sleep Medicine Network

Respiratory-Related Sleep Disorders Section

Considering the recent Olympics, it is timely to review the importance of sleep for optimal athletic performance. When surveyed, 20% to 50% of athletes report poor or insufficient sleep, with consequences across four categories.^1,2

Athletic performance: Objective measures of athletic performance, such as oxygen-carrying capacity during cardiopulmonary exercise and even sport-specific accuracy measures, like shooting percentage in basketball, have been shown to worsen with decreased sleep.

CHEST

CHEST

References

1. Cook JD, Charest J. Sleep and performance in professional athletes. Curr Sleep Med Rep. 2023;9(1):56-81.



2. Charest J, Grandner MA. Sleep and athletic performance: impacts on physical performance, mental performance, injury risk and recovery, and mental health. Sleep Med Clin. 2020;15(1):41-57.

COPENHAGEN — Women of childbearing age with multiple sclerosis (MS) receive fewer highly effective medications than do men with similar levels of disability, even after accounting for treatment discontinuations during pregnancy and the postpartum period, new research suggested.

“We believe that pregnancy-related considerations probably still explain the major part of this gap,” said Antoine Gavoille, MD, University of Lyon, France, who presented the study at the 2024 ECTRIMS annual meeting.

This is likely due to “factors such as anticipation of pregnancy long before it occurs and fear of exposing women of childbearing age to certain treatments even in the absence of planned pregnancy,” he added.

Caution is warranted when medications are first marketed because there are no data on safety in pregnancy. However, in 2024, “this lesser treatment in women is unacceptable,” said Dr. Gavoille. “We now have several highly effective treatment options which are compatible with pregnancy,” he noted.

The researchers analyzed the French MS registry of 22,657 patients with relapsing MS (74.2% women) between 1997 and 2022 for treatment differences between women and their male counterparts. The results were adjusted for multiple factors including educational level, disease activity, disability levels, and discontinuation of drugs during pregnancy.

They found that over a median follow-up of 11.6 years, women had a significantly lower probability of receiving any disease-modifying treatment (odds ratio [OR], 0.92; 95% CI, 0.87-0.97).

In addition, women were even less likely to receive high-efficacy treatments such as natalizumab, anti-CD20 antibodies, or S1P modulators such as fingolimod (OR, 0.80; 95% CI, 0.74-0.86).

The difference in disease-modifying treatment usage varied across different treatments and over time. Teriflunomide, fingolimod, and anti-CD20 therapies were significantly underused throughout their entire availability (OR, 0.87, 0.78, and 0.80, respectively).

Interferon and natalizumab were initially used less frequently in women, but the use of these medications equalized over time.

In contrast, glatiramer acetate and dimethyl fumarate were initially used equally between genders but eventually became more commonly prescribed to women (OR, 1.27 and 1.17, respectively).

The disparity in treatment emerged after 2 years of disease duration for disease-modifying treatments in general and as early as 1 year for highly effective treatments.

The gender-based treatment gap did not significantly vary with patient age, indicating that therapeutic inertia may persist regardless of a woman’s age.

“Women may not be receiving the most effective therapies at the optimal time, often due to concerns about pregnancy risks that may never materialize,” said the study’s lead investigator Sandra Vukusic, MD, Lyon University Hospital, France.

“The main impact of this therapeutic inertia in women is the less effective control of disease activity, leading to the accumulation of lesions and an increased risk of long-term disability. This represents a real loss of opportunity for women, especially in an era where disease-modifying treatments so effective when used early,” she added.

Dr. Gavoille said that recommendations in France allow the use of moderately active drugs, including interferon and glatiramer acetate, during pregnancy or in women planning a pregnancy. More recently there has been enough data to allow the use of natalizumab up until the second trimester.

In addition, although not in the guidelines, it is thought that the anti-CD20 monoclonal antibodies, such as rituximab or ocrelizumab, may be safe as they are very long acting. Women can be dosed before pregnancy and be covered for the whole pregnancy period without exposing the fetus to the drug, he explained.

“The message is that now we have both moderately and highly effective treatments that are compatible with a pregnancy plan,” Dr. Gavoille said.

First, clinicians have to select a level of treatment based on disease activity and then choose the best option, depending on the woman’s plans with respect to pregnancy.

Drugs that are contraindicated in pregnancy include teriflunomide and S1P modulators such as fingolimod, which have been shown to be harmful to the fetus.

“But they could still be used in women of childbearing years as long as they are not planning a pregnancy and understand the need for contraception,” Dr. Gavoille noted.

He believes both neurologists and patients are afraid of using drugs in pregnancy. “It is, of course, important to be cautious on this issue, but we should not let fear stop these women receiving the best treatments available.”

However, he added, clinical practice is changing, and confidence is gradually building around using highly effective treatments in women of childbearing age.

Dr. Gavoille also called for more research to collate data in pregnant women with MS who are exposed to various treatments, starting with case reports and then academic registries, which he described as “difficult but important work.”

Commenting on the study, Robert Hoepner, MD, University Hospital of Bern, Switzerland, agreed that this treatment disparity between men and women is “unacceptable.”

Dr. Hoepner noted that a recent study showed that women have different relapse symptoms than men, which may also affect treatment choice.

Dr. Gavoille responded that other research has shown that women are less likely to have treatment escalation post-relapse. “This could be because of a difference in symptoms. But this is something we haven’t looked at yet.” 

Also commenting on the research, Frauke Zipp, MD, University Medical Center Mainz in Germany, said it would be interesting to follow this cohort over the long term to see if the women do less well several years down the line.

The study authors and commentators reported no relevant disclosures.
 

A version of this article first appeared on Medscape.com.

COPENHAGEN — Women of childbearing age with multiple sclerosis (MS) receive fewer highly effective medications than do men with similar levels of disability, even after accounting for treatment discontinuations during pregnancy and the postpartum period, new research suggested.

“We believe that pregnancy-related considerations probably still explain the major part of this gap,” said Antoine Gavoille, MD, University of Lyon, France, who presented the study at the 2024 ECTRIMS annual meeting.

This is likely due to “factors such as anticipation of pregnancy long before it occurs and fear of exposing women of childbearing age to certain treatments even in the absence of planned pregnancy,” he added.

Caution is warranted when medications are first marketed because there are no data on safety in pregnancy. However, in 2024, “this lesser treatment in women is unacceptable,” said Dr. Gavoille. “We now have several highly effective treatment options which are compatible with pregnancy,” he noted.

The researchers analyzed the French MS registry of 22,657 patients with relapsing MS (74.2% women) between 1997 and 2022 for treatment differences between women and their male counterparts. The results were adjusted for multiple factors including educational level, disease activity, disability levels, and discontinuation of drugs during pregnancy.

They found that over a median follow-up of 11.6 years, women had a significantly lower probability of receiving any disease-modifying treatment (odds ratio [OR], 0.92; 95% CI, 0.87-0.97).

In addition, women were even less likely to receive high-efficacy treatments such as natalizumab, anti-CD20 antibodies, or S1P modulators such as fingolimod (OR, 0.80; 95% CI, 0.74-0.86).

The difference in disease-modifying treatment usage varied across different treatments and over time. Teriflunomide, fingolimod, and anti-CD20 therapies were significantly underused throughout their entire availability (OR, 0.87, 0.78, and 0.80, respectively).

Interferon and natalizumab were initially used less frequently in women, but the use of these medications equalized over time.

In contrast, glatiramer acetate and dimethyl fumarate were initially used equally between genders but eventually became more commonly prescribed to women (OR, 1.27 and 1.17, respectively).

The disparity in treatment emerged after 2 years of disease duration for disease-modifying treatments in general and as early as 1 year for highly effective treatments.

The gender-based treatment gap did not significantly vary with patient age, indicating that therapeutic inertia may persist regardless of a woman’s age.

“Women may not be receiving the most effective therapies at the optimal time, often due to concerns about pregnancy risks that may never materialize,” said the study’s lead investigator Sandra Vukusic, MD, Lyon University Hospital, France.

“The main impact of this therapeutic inertia in women is the less effective control of disease activity, leading to the accumulation of lesions and an increased risk of long-term disability. This represents a real loss of opportunity for women, especially in an era where disease-modifying treatments so effective when used early,” she added.

Dr. Gavoille said that recommendations in France allow the use of moderately active drugs, including interferon and glatiramer acetate, during pregnancy or in women planning a pregnancy. More recently there has been enough data to allow the use of natalizumab up until the second trimester.

In addition, although not in the guidelines, it is thought that the anti-CD20 monoclonal antibodies, such as rituximab or ocrelizumab, may be safe as they are very long acting. Women can be dosed before pregnancy and be covered for the whole pregnancy period without exposing the fetus to the drug, he explained.

“The message is that now we have both moderately and highly effective treatments that are compatible with a pregnancy plan,” Dr. Gavoille said.

First, clinicians have to select a level of treatment based on disease activity and then choose the best option, depending on the woman’s plans with respect to pregnancy.

Drugs that are contraindicated in pregnancy include teriflunomide and S1P modulators such as fingolimod, which have been shown to be harmful to the fetus.

“But they could still be used in women of childbearing years as long as they are not planning a pregnancy and understand the need for contraception,” Dr. Gavoille noted.

He believes both neurologists and patients are afraid of using drugs in pregnancy. “It is, of course, important to be cautious on this issue, but we should not let fear stop these women receiving the best treatments available.”

However, he added, clinical practice is changing, and confidence is gradually building around using highly effective treatments in women of childbearing age.

Dr. Gavoille also called for more research to collate data in pregnant women with MS who are exposed to various treatments, starting with case reports and then academic registries, which he described as “difficult but important work.”

Commenting on the study, Robert Hoepner, MD, University Hospital of Bern, Switzerland, agreed that this treatment disparity between men and women is “unacceptable.”

Dr. Hoepner noted that a recent study showed that women have different relapse symptoms than men, which may also affect treatment choice.

Dr. Gavoille responded that other research has shown that women are less likely to have treatment escalation post-relapse. “This could be because of a difference in symptoms. But this is something we haven’t looked at yet.” 

Also commenting on the research, Frauke Zipp, MD, University Medical Center Mainz in Germany, said it would be interesting to follow this cohort over the long term to see if the women do less well several years down the line.

The study authors and commentators reported no relevant disclosures.
 

A version of this article first appeared on Medscape.com.

COPENHAGEN — Women of childbearing age with multiple sclerosis (MS) receive fewer highly effective medications than do men with similar levels of disability, even after accounting for treatment discontinuations during pregnancy and the postpartum period, new research suggested.

“We believe that pregnancy-related considerations probably still explain the major part of this gap,” said Antoine Gavoille, MD, University of Lyon, France, who presented the study at the 2024 ECTRIMS annual meeting.

This is likely due to “factors such as anticipation of pregnancy long before it occurs and fear of exposing women of childbearing age to certain treatments even in the absence of planned pregnancy,” he added.

Caution is warranted when medications are first marketed because there are no data on safety in pregnancy. However, in 2024, “this lesser treatment in women is unacceptable,” said Dr. Gavoille. “We now have several highly effective treatment options which are compatible with pregnancy,” he noted.

The researchers analyzed the French MS registry of 22,657 patients with relapsing MS (74.2% women) between 1997 and 2022 for treatment differences between women and their male counterparts. The results were adjusted for multiple factors including educational level, disease activity, disability levels, and discontinuation of drugs during pregnancy.

They found that over a median follow-up of 11.6 years, women had a significantly lower probability of receiving any disease-modifying treatment (odds ratio [OR], 0.92; 95% CI, 0.87-0.97).

In addition, women were even less likely to receive high-efficacy treatments such as natalizumab, anti-CD20 antibodies, or S1P modulators such as fingolimod (OR, 0.80; 95% CI, 0.74-0.86).

The difference in disease-modifying treatment usage varied across different treatments and over time. Teriflunomide, fingolimod, and anti-CD20 therapies were significantly underused throughout their entire availability (OR, 0.87, 0.78, and 0.80, respectively).

Interferon and natalizumab were initially used less frequently in women, but the use of these medications equalized over time.

In contrast, glatiramer acetate and dimethyl fumarate were initially used equally between genders but eventually became more commonly prescribed to women (OR, 1.27 and 1.17, respectively).

The disparity in treatment emerged after 2 years of disease duration for disease-modifying treatments in general and as early as 1 year for highly effective treatments.

The gender-based treatment gap did not significantly vary with patient age, indicating that therapeutic inertia may persist regardless of a woman’s age.

“Women may not be receiving the most effective therapies at the optimal time, often due to concerns about pregnancy risks that may never materialize,” said the study’s lead investigator Sandra Vukusic, MD, Lyon University Hospital, France.

“The main impact of this therapeutic inertia in women is the less effective control of disease activity, leading to the accumulation of lesions and an increased risk of long-term disability. This represents a real loss of opportunity for women, especially in an era where disease-modifying treatments so effective when used early,” she added.

Dr. Gavoille said that recommendations in France allow the use of moderately active drugs, including interferon and glatiramer acetate, during pregnancy or in women planning a pregnancy. More recently there has been enough data to allow the use of natalizumab up until the second trimester.

In addition, although not in the guidelines, it is thought that the anti-CD20 monoclonal antibodies, such as rituximab or ocrelizumab, may be safe as they are very long acting. Women can be dosed before pregnancy and be covered for the whole pregnancy period without exposing the fetus to the drug, he explained.

“The message is that now we have both moderately and highly effective treatments that are compatible with a pregnancy plan,” Dr. Gavoille said.

First, clinicians have to select a level of treatment based on disease activity and then choose the best option, depending on the woman’s plans with respect to pregnancy.

Drugs that are contraindicated in pregnancy include teriflunomide and S1P modulators such as fingolimod, which have been shown to be harmful to the fetus.

“But they could still be used in women of childbearing years as long as they are not planning a pregnancy and understand the need for contraception,” Dr. Gavoille noted.

He believes both neurologists and patients are afraid of using drugs in pregnancy. “It is, of course, important to be cautious on this issue, but we should not let fear stop these women receiving the best treatments available.”

However, he added, clinical practice is changing, and confidence is gradually building around using highly effective treatments in women of childbearing age.

Dr. Gavoille also called for more research to collate data in pregnant women with MS who are exposed to various treatments, starting with case reports and then academic registries, which he described as “difficult but important work.”

Commenting on the study, Robert Hoepner, MD, University Hospital of Bern, Switzerland, agreed that this treatment disparity between men and women is “unacceptable.”

Dr. Hoepner noted that a recent study showed that women have different relapse symptoms than men, which may also affect treatment choice.

Dr. Gavoille responded that other research has shown that women are less likely to have treatment escalation post-relapse. “This could be because of a difference in symptoms. But this is something we haven’t looked at yet.” 

Also commenting on the research, Frauke Zipp, MD, University Medical Center Mainz in Germany, said it would be interesting to follow this cohort over the long term to see if the women do less well several years down the line.

The study authors and commentators reported no relevant disclosures.
 

A version of this article first appeared on Medscape.com.

Diffuse Lung Disease and Lung Transplant Network

Occupational and Environmental Health Section

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The kitchen is considered the heart of the home, but recent discoveries have raised concerns about whether this beloved space might also pose hidden health risks. Gas stoves, present in 38% of U.S. homes, generate multiple pollutants including nitrogen dioxide (NO₂), a known respiratory irritant.¹ Studies have identified a correlation between NO₂ levels and respiratory conditions, with children being particularly vulnerable.² The association between domestic NO₂ exposure from gas stoves and conditions such as asthma has led to increased scrutiny of indoor air quality.

Studies have demonstrated that households using gas stoves have higher indoor NO₂ levels, with levels that far exceed the EPA national ambient air quality standards.³ While the predominance of studies have looked at a correlation with pediatric pulmonary processes, there is also evidence of increased lung function loss in patients who smoke and have COPD.⁴

Switching from gas to electric stoves is one proposed solution to mitigate exposure to NO₂. Evidence suggests that electric stoves significantly reduce indoor NO₂ levels, lowering the risk of respiratory illnesses.

Another proposed solution has been to utilize hoods; however, capture efficiency is variable and some recycle the air and return it indoors.⁵ While existing data indicates a connection between gas stove use and respiratory health risks, conclusive evidence examining the magnitude and mechanisms linking these factors to chronic lung diseases is still needed. Comprehensive studies will help determine whether the kitchen staple—a gas stove—is indeed a friend or a foe to our respiratory health.

References

1. U.S. Energy Information Administration, Appliances in U.S. homes, by household income, 2020. https://www.eia.gov/consumption/residential/data/2020/hc/pdf/HC%203.5.pdf. Accessed September 10, 2024.

2. Belanger K, Holford TR, Gent JF, Hill ME, Kezik JM, Leaderer BP. Household levels of nitrogen dioxide and pediatric asthma severity. Epidemiology. 2013;24(2):320-330.

3. Singer BC, Pass RZ, Delp WW, Lorenzetti DM, Maddalena RL. Pollutant concentrations and emission rates from natural gas cooking burners without and with range hood exhaust in nine California homes. Building and Environment. 2017;122:215-229.

4. Hansel NN, Woo H, Koehler K, et al. Indoor pollution and lung function decline in current and former smokers: SPIROMICS AIR. Am J Respir Crit Care Med. 2023;208(10):1042-1051.

5. Nassikas NJ, McCormack MC, Ewart G, et al. Indoor air sources of outdoor air pollution: health consequences, policy, and recommendations: an Official American Thoracic Society Workshop report. Ann Am Thorac Soc. 2024;21(3), 365-376.

Diffuse Lung Disease and Lung Transplant Network

Occupational and Environmental Health Section

CHEST

CHEST

CHEST

The kitchen is considered the heart of the home, but recent discoveries have raised concerns about whether this beloved space might also pose hidden health risks. Gas stoves, present in 38% of U.S. homes, generate multiple pollutants including nitrogen dioxide (NO₂), a known respiratory irritant.¹ Studies have identified a correlation between NO₂ levels and respiratory conditions, with children being particularly vulnerable.² The association between domestic NO₂ exposure from gas stoves and conditions such as asthma has led to increased scrutiny of indoor air quality.

Studies have demonstrated that households using gas stoves have higher indoor NO₂ levels, with levels that far exceed the EPA national ambient air quality standards.³ While the predominance of studies have looked at a correlation with pediatric pulmonary processes, there is also evidence of increased lung function loss in patients who smoke and have COPD.⁴

Switching from gas to electric stoves is one proposed solution to mitigate exposure to NO₂. Evidence suggests that electric stoves significantly reduce indoor NO₂ levels, lowering the risk of respiratory illnesses.

Another proposed solution has been to utilize hoods; however, capture efficiency is variable and some recycle the air and return it indoors.⁵ While existing data indicates a connection between gas stove use and respiratory health risks, conclusive evidence examining the magnitude and mechanisms linking these factors to chronic lung diseases is still needed. Comprehensive studies will help determine whether the kitchen staple—a gas stove—is indeed a friend or a foe to our respiratory health.

References

1. U.S. Energy Information Administration, Appliances in U.S. homes, by household income, 2020. https://www.eia.gov/consumption/residential/data/2020/hc/pdf/HC%203.5.pdf. Accessed September 10, 2024.

2. Belanger K, Holford TR, Gent JF, Hill ME, Kezik JM, Leaderer BP. Household levels of nitrogen dioxide and pediatric asthma severity. Epidemiology. 2013;24(2):320-330.

3. Singer BC, Pass RZ, Delp WW, Lorenzetti DM, Maddalena RL. Pollutant concentrations and emission rates from natural gas cooking burners without and with range hood exhaust in nine California homes. Building and Environment. 2017;122:215-229.

4. Hansel NN, Woo H, Koehler K, et al. Indoor pollution and lung function decline in current and former smokers: SPIROMICS AIR. Am J Respir Crit Care Med. 2023;208(10):1042-1051.

5. Nassikas NJ, McCormack MC, Ewart G, et al. Indoor air sources of outdoor air pollution: health consequences, policy, and recommendations: an Official American Thoracic Society Workshop report. Ann Am Thorac Soc. 2024;21(3), 365-376.

Diffuse Lung Disease and Lung Transplant Network

Occupational and Environmental Health Section

CHEST

CHEST

CHEST

The kitchen is considered the heart of the home, but recent discoveries have raised concerns about whether this beloved space might also pose hidden health risks. Gas stoves, present in 38% of U.S. homes, generate multiple pollutants including nitrogen dioxide (NO₂), a known respiratory irritant.¹ Studies have identified a correlation between NO₂ levels and respiratory conditions, with children being particularly vulnerable.² The association between domestic NO₂ exposure from gas stoves and conditions such as asthma has led to increased scrutiny of indoor air quality.

Studies have demonstrated that households using gas stoves have higher indoor NO₂ levels, with levels that far exceed the EPA national ambient air quality standards.³ While the predominance of studies have looked at a correlation with pediatric pulmonary processes, there is also evidence of increased lung function loss in patients who smoke and have COPD.⁴

Switching from gas to electric stoves is one proposed solution to mitigate exposure to NO₂. Evidence suggests that electric stoves significantly reduce indoor NO₂ levels, lowering the risk of respiratory illnesses.

Another proposed solution has been to utilize hoods; however, capture efficiency is variable and some recycle the air and return it indoors.⁵ While existing data indicates a connection between gas stove use and respiratory health risks, conclusive evidence examining the magnitude and mechanisms linking these factors to chronic lung diseases is still needed. Comprehensive studies will help determine whether the kitchen staple—a gas stove—is indeed a friend or a foe to our respiratory health.

References

1. U.S. Energy Information Administration, Appliances in U.S. homes, by household income, 2020. https://www.eia.gov/consumption/residential/data/2020/hc/pdf/HC%203.5.pdf. Accessed September 10, 2024.

2. Belanger K, Holford TR, Gent JF, Hill ME, Kezik JM, Leaderer BP. Household levels of nitrogen dioxide and pediatric asthma severity. Epidemiology. 2013;24(2):320-330.

3. Singer BC, Pass RZ, Delp WW, Lorenzetti DM, Maddalena RL. Pollutant concentrations and emission rates from natural gas cooking burners without and with range hood exhaust in nine California homes. Building and Environment. 2017;122:215-229.

4. Hansel NN, Woo H, Koehler K, et al. Indoor pollution and lung function decline in current and former smokers: SPIROMICS AIR. Am J Respir Crit Care Med. 2023;208(10):1042-1051.

5. Nassikas NJ, McCormack MC, Ewart G, et al. Indoor air sources of outdoor air pollution: health consequences, policy, and recommendations: an Official American Thoracic Society Workshop report. Ann Am Thorac Soc. 2024;21(3), 365-376.

Critical Care Network

Sepsis/Shock Section

Early recognition is the linchpin of sepsis management, as mortality from sepsis increases by 4% to 9% for every hour that diagnosis and treatment are delayed.^1,2 Artificial intelligence (AI) and machine learning (ML) are increasingly featured in discussions and publications about sepsis care. Already ML models are embedded in electronic medical records (EMR), driving best-practice advisories that are presented to users.³ Epic, the EMR that serves over half of patients in the US, offers its own proprietary cognitive computing model for early detection.

CHEST

CHEST

References

1. Sepsis Alliance. (2024, June 19). Septic shock. 2024. https://www.sepsis.org/sepsisand/septic-shock/. Accessed September 10, 2024.

2. Djikic M, Milenkovic M, Stojadinovic M, et al. The six scoring systems’ prognostic value in predicting 24-hour mortality in septic patients. Eur Rev Med Pharmacol Sci. 2024;28(12):3849-3859.

3. Kamran F, Tjandra D, Heiler A, et al. Evaluation of sepsis prediction models before onset of treatment. NEJM AI. 2024.

4. Lilly CM, Kirk D, Pessach IM, et al. Application of machine learning models to biomedical and information system signals from critically ill adults. CHEST. 2024;165(5):1139-1148.
 

Critical Care Network

Sepsis/Shock Section

Early recognition is the linchpin of sepsis management, as mortality from sepsis increases by 4% to 9% for every hour that diagnosis and treatment are delayed.^1,2 Artificial intelligence (AI) and machine learning (ML) are increasingly featured in discussions and publications about sepsis care. Already ML models are embedded in electronic medical records (EMR), driving best-practice advisories that are presented to users.³ Epic, the EMR that serves over half of patients in the US, offers its own proprietary cognitive computing model for early detection.

CHEST

CHEST

References

1. Sepsis Alliance. (2024, June 19). Septic shock. 2024. https://www.sepsis.org/sepsisand/septic-shock/. Accessed September 10, 2024.

2. Djikic M, Milenkovic M, Stojadinovic M, et al. The six scoring systems’ prognostic value in predicting 24-hour mortality in septic patients. Eur Rev Med Pharmacol Sci. 2024;28(12):3849-3859.

3. Kamran F, Tjandra D, Heiler A, et al. Evaluation of sepsis prediction models before onset of treatment. NEJM AI. 2024.

4. Lilly CM, Kirk D, Pessach IM, et al. Application of machine learning models to biomedical and information system signals from critically ill adults. CHEST. 2024;165(5):1139-1148.
 

Critical Care Network

Sepsis/Shock Section

Early recognition is the linchpin of sepsis management, as mortality from sepsis increases by 4% to 9% for every hour that diagnosis and treatment are delayed.^1,2 Artificial intelligence (AI) and machine learning (ML) are increasingly featured in discussions and publications about sepsis care. Already ML models are embedded in electronic medical records (EMR), driving best-practice advisories that are presented to users.³ Epic, the EMR that serves over half of patients in the US, offers its own proprietary cognitive computing model for early detection.

CHEST

CHEST

References

1. Sepsis Alliance. (2024, June 19). Septic shock. 2024. https://www.sepsis.org/sepsisand/septic-shock/. Accessed September 10, 2024.

2. Djikic M, Milenkovic M, Stojadinovic M, et al. The six scoring systems’ prognostic value in predicting 24-hour mortality in septic patients. Eur Rev Med Pharmacol Sci. 2024;28(12):3849-3859.

3. Kamran F, Tjandra D, Heiler A, et al. Evaluation of sepsis prediction models before onset of treatment. NEJM AI. 2024.

4. Lilly CM, Kirk D, Pessach IM, et al. Application of machine learning models to biomedical and information system signals from critically ill adults. CHEST. 2024;165(5):1139-1148.
 

Thoracic Oncology and Chest Procedures Network

Ultrasound and Chest Imaging Section

An assessment using bedside thoracic ultrasound (TUS) improves diagnostic evaluation and therapeutic management in critically ill patients without undue risk. With changes in diagnosis occurring in 23% of cases and alterations in management in 39% of critically ill patients, TUS can improve length of stay, reduce complications, minimize delays in therapy, and lower hospitalization costs.¹ Compared with its cardiac counterpart, attaining proficiency in lung ultrasound (LUS) is easier.² Intensivists are at risk of forgoing mastering LUS in favor of developing more difficult skills. Proficiency in LUS is essential, as more than half of TUS evaluations are for respiratory complaints and most findings are pulmonary.¹

CHEST

A quick bedside assessment outperforms chest radiographs and available clinical scores in distinguishing pneumonia from atelectasis. The presence of dynamic air bronchograms within the consolidation is 45% sensitive and 99% specific for pneumonia over atelectasis.³ When air bronchograms are static, the presence of flow on color Doppler is 98% sensitive and 68% specific for pneumonia over atelectasis. Similarly, a closer look at the pleural lining shows more than the presence or absence of lung sliding. The presence of fragmentation, irregularity, or thickening of pleural lines provides 100% specificity in discriminating a noncardiogenic interstitial pathology from cardiogenic pulmonary edema.⁴

CHEST

References

1. Heldeweg M, Lopez Matta JE, Pisani L, Slot S. The impact of thoracic ultrasound on clinical management of critically ill patients (UltraMan): an international prospective observational study. Crit Care Med. 2023;51:357-364.

2. Kraaijenbrink BVC, Mousa A, Bos LD, et al. Defining basic (lung) ultrasound skills: not so basic after all? Intensive Care Med. 2022;48:628–629.

3. Haaksma M, Smit J, Heldeweg M, Nooitgedacht J, de Grooth H. Extended lung ultrasound to differentiate between pneumonia and atelectasis in critically ill patients: a diagnostic accuracy study. Crit Care Med. 2022;50:750-759.

4. Heldeweg M, Smit M, Kramer-Elliott S, et al. Lung ultrasound signs to diagnose and discriminate interstitial syndromes in ICU patients: a diagnostic accuracy study in two cohorts. Crit Care Med. 2022;50(11):1607-1617.
 

Thoracic Oncology and Chest Procedures Network

Ultrasound and Chest Imaging Section

An assessment using bedside thoracic ultrasound (TUS) improves diagnostic evaluation and therapeutic management in critically ill patients without undue risk. With changes in diagnosis occurring in 23% of cases and alterations in management in 39% of critically ill patients, TUS can improve length of stay, reduce complications, minimize delays in therapy, and lower hospitalization costs.¹ Compared with its cardiac counterpart, attaining proficiency in lung ultrasound (LUS) is easier.² Intensivists are at risk of forgoing mastering LUS in favor of developing more difficult skills. Proficiency in LUS is essential, as more than half of TUS evaluations are for respiratory complaints and most findings are pulmonary.¹

CHEST

A quick bedside assessment outperforms chest radiographs and available clinical scores in distinguishing pneumonia from atelectasis. The presence of dynamic air bronchograms within the consolidation is 45% sensitive and 99% specific for pneumonia over atelectasis.³ When air bronchograms are static, the presence of flow on color Doppler is 98% sensitive and 68% specific for pneumonia over atelectasis. Similarly, a closer look at the pleural lining shows more than the presence or absence of lung sliding. The presence of fragmentation, irregularity, or thickening of pleural lines provides 100% specificity in discriminating a noncardiogenic interstitial pathology from cardiogenic pulmonary edema.⁴

CHEST

References

1. Heldeweg M, Lopez Matta JE, Pisani L, Slot S. The impact of thoracic ultrasound on clinical management of critically ill patients (UltraMan): an international prospective observational study. Crit Care Med. 2023;51:357-364.

2. Kraaijenbrink BVC, Mousa A, Bos LD, et al. Defining basic (lung) ultrasound skills: not so basic after all? Intensive Care Med. 2022;48:628–629.

3. Haaksma M, Smit J, Heldeweg M, Nooitgedacht J, de Grooth H. Extended lung ultrasound to differentiate between pneumonia and atelectasis in critically ill patients: a diagnostic accuracy study. Crit Care Med. 2022;50:750-759.

4. Heldeweg M, Smit M, Kramer-Elliott S, et al. Lung ultrasound signs to diagnose and discriminate interstitial syndromes in ICU patients: a diagnostic accuracy study in two cohorts. Crit Care Med. 2022;50(11):1607-1617.
 

Thoracic Oncology and Chest Procedures Network

Ultrasound and Chest Imaging Section

An assessment using bedside thoracic ultrasound (TUS) improves diagnostic evaluation and therapeutic management in critically ill patients without undue risk. With changes in diagnosis occurring in 23% of cases and alterations in management in 39% of critically ill patients, TUS can improve length of stay, reduce complications, minimize delays in therapy, and lower hospitalization costs.¹ Compared with its cardiac counterpart, attaining proficiency in lung ultrasound (LUS) is easier.² Intensivists are at risk of forgoing mastering LUS in favor of developing more difficult skills. Proficiency in LUS is essential, as more than half of TUS evaluations are for respiratory complaints and most findings are pulmonary.¹

CHEST

A quick bedside assessment outperforms chest radiographs and available clinical scores in distinguishing pneumonia from atelectasis. The presence of dynamic air bronchograms within the consolidation is 45% sensitive and 99% specific for pneumonia over atelectasis.³ When air bronchograms are static, the presence of flow on color Doppler is 98% sensitive and 68% specific for pneumonia over atelectasis. Similarly, a closer look at the pleural lining shows more than the presence or absence of lung sliding. The presence of fragmentation, irregularity, or thickening of pleural lines provides 100% specificity in discriminating a noncardiogenic interstitial pathology from cardiogenic pulmonary edema.⁴

CHEST

References

1. Heldeweg M, Lopez Matta JE, Pisani L, Slot S. The impact of thoracic ultrasound on clinical management of critically ill patients (UltraMan): an international prospective observational study. Crit Care Med. 2023;51:357-364.

2. Kraaijenbrink BVC, Mousa A, Bos LD, et al. Defining basic (lung) ultrasound skills: not so basic after all? Intensive Care Med. 2022;48:628–629.

3. Haaksma M, Smit J, Heldeweg M, Nooitgedacht J, de Grooth H. Extended lung ultrasound to differentiate between pneumonia and atelectasis in critically ill patients: a diagnostic accuracy study. Crit Care Med. 2022;50:750-759.

4. Heldeweg M, Smit M, Kramer-Elliott S, et al. Lung ultrasound signs to diagnose and discriminate interstitial syndromes in ICU patients: a diagnostic accuracy study in two cohorts. Crit Care Med. 2022;50(11):1607-1617.
 

Gitanjali Srivastava, MD, professor of medicine, pediatrics, and surgery, and medical director of obesity medicine at Vanderbilt University School of Medicine in Nashville, Tennessee, was nearly 10 years into practicing pediatric medicine when she graduated from the obesity medicine fellowship at Massachusetts General Hospital in Boston in 2013. “We were the very first sort of fellows to speak of then; there were no standards or curriculum,” she said.

Obesity was already epidemic, but stigma and bias were still pervasive in the medical community and within the public. After graduating, Dr. Srivastava spent months vying for a position with hospital CEOs. She traveled across the country explaining the specialty and its value, going into detail about the budget, business model, space requirement, and revenue potential of obesity medicine. 

Today marks a very different era.

Obesity medicine is exploding. Patients are spilling into doctors’ offices looking for obesity treatment. Healthcare systems are seeking out obesity specialists and building metabolic health centers. Since 2020, the number of doctors board-certified by the American Board of Obesity Medicine has nearly doubled, and the number of obesity medicine fellowships across the country has more than doubled. Next month, another 2115 doctors from primary care, surgery, orthopedics, pediatrics, fertility, endocrinology, and beyond will sit for the 2024 exam. The once niche specialty is quickly becoming intertwined with most of modern medicine.
 

The Need to Treat

It’s no mystery that the rapid expansion of obesity medicine coincides with the US Food and Drug Administration’s approval of GLP-1 injections. The drugs’ radical weight loss properties have captured headlines and driven up patient demand. Meanwhile, doctors are finally able to offer effective treatment for a disease that affects 40% of US adults.

“We are finally treating it as a chronic disease, not as a lifestyle,” said Marcio Griebeler, MD, director of the obesity medicine fellowship at the Cleveland Clinic. And “I think it’s fulfilling for physicians,” he said. 

For so long, the advice for obesity was about lifestyle. Move more, eat less, and harness willpower, “which really is a fallacy,” said Kimberly Gudzune, MD, MPH, an obesity medicine specialist and chief medical officer for the American Board of Obesity Medicine (ABOM) Foundation. For people with obesity, “your brain is operating differently,” she said. “Your body really is set up to work against you.” 

Brianna Johnson-Rabbett, MD, medical director of the ABOM, told this news organization that with the advent of GLP-1s, “there’s a clearer recognition that obesity is a disease that needs to be treated like other diseases.” Some of that is thanks to clinical trial data showing that just as with other diseases such as high blood pressure or diabetes, obesity can be treated with medication and it resurges when the medication is stopped, she said.

Doctors don’t have to go looking for patients with obesity, dr. Griebeler added. Now that treatment options exist, they’re showing up in droves at the doctor’s office — all the doctors’ offices. In primary care, endocrinology, surgery, pediatrics — a wide variety of doctors are being asked about obesity drugs, Dr. Griebeler noted.

And while doctors are often just as excited as patients about the potential for treatment, many find themselves under-equipped when it comes to obesity. “More physicians are ... recognizing the value in treating this, and some are realizing, “Oh gosh, I never learned how to do this,” said Dr. Gudzune.
 

Information Patients Have Been Waiting For

Medical training has traditionally devoted minimal, if any, curriculum to obesity and metabolism. “To be honest, we didn’t really cover this at all in my training,” said Nina Paddu, MD, obesity medicine specialist at Maimonides Medical Center in New York City who finished her training only 2 years ago. “The guidance even in residency was ‘let’s send them to nutrition’ and ‘recommend exercising.’ ”

In addition to the medical education gap, until recently there was a “paucity of robust evidence,” Dr. Srivastava said. Leaders in the field wanted to establish standards and guidelines, but there wasn’t enough strong evidence on obesity and its treatments to build them, she said. 

Only in the last 5 years or so has the evidence-based understanding of obesity’s pathophysiology truly accelerated: The brain’s driving roles, its interplay with hormones, and its interactions with other diseases. “We are just at the cusp of understanding all the different factors,” Dr. Gudzune said.

But already endocrinologists, surgeons, fertility specialists, gynecologists, and oncologists, to name a few, see the critical overlap with their own field. “Conditions were once suspected of being intertwined [with obesity], and now we have data to connect them,” Dr. Srivastava said. For example, there’s now data connecting semaglutide to a 20% reduction in cardiovascular events for people with obesity. That’s a game changer for multiple specialties, she told this news organization. 
 

Getting Trained in Obesity Management

The recent uptick in obesity insights and increased patient need has doctors from every career stage seeking additional training.

The ABOM offers two board certification pathways: 60 hours of CME credits or a 12-month fellowship. Both paths require doctors to pass the board’s exam. 

Many doctors incorporate the training into their existing practice. The CME credit pathway, especially, is designed to help get doctors up to speed without requiring them to upend their lives for a fellowship.

Dr. Srivastava said that the fellowship is more consuming and immersive. While it’s often younger doctors just out of training who apply to fellowship, every year, “I’m astonished at the number of talented physicians with clinical and research experience who want to immerse themselves in a fellowship experience.”

Some doctors return to their previous specialties after fellowship. But many will go on to take obesity medicine–specific roles or set aside clinic hours for obesity medicine. Their credentials are “really attractive to institutions, especially those looking to open up obesity medicine or weight management programs,” said Dr. Srivastava.

Dr. Paddu, who finished her obesity medicine fellowship this year, said there are a variety of obesity medicine jobs to choose from — far different from Dr. Srivastava’s job search 15 years ago. Dr. Paddu’s new role combines 2 days of primary care with 2 days devoted to obesity medicine and 1 day each week set aside for administrative work so she can build up the hospital’s new metabolic health clinic. 
 

Still Not Enough Obesity Specialists

As with all things, rapid growth requires careful oversight. “Part of the responsibility of the board is to think critically of how the field is growing” and conduct ongoing monitoring, Dr. Gudzune said.

This is also why the board’s credentials are time-limited and must be recertified, Dr. Johnson-Rabbett added. 

But even with the rise in certified doctors and obesity medicine positions, the 8263 doctors certified by ABOM are only a tiny fraction of US physicians. As a result, there’s genuine likelihood that many patients seeking GLP-1s or other obesity treatment don’t yet have access to the holistic care they need. Plus, doctors may still not have obesity expertise within their networks.

“The field has grown rapidly, but it’s still such a small field relative to the patient need,” said Dr. Gudzune.
 

A version of this article appeared on Medscape.com.

Gitanjali Srivastava, MD, professor of medicine, pediatrics, and surgery, and medical director of obesity medicine at Vanderbilt University School of Medicine in Nashville, Tennessee, was nearly 10 years into practicing pediatric medicine when she graduated from the obesity medicine fellowship at Massachusetts General Hospital in Boston in 2013. “We were the very first sort of fellows to speak of then; there were no standards or curriculum,” she said.

Obesity was already epidemic, but stigma and bias were still pervasive in the medical community and within the public. After graduating, Dr. Srivastava spent months vying for a position with hospital CEOs. She traveled across the country explaining the specialty and its value, going into detail about the budget, business model, space requirement, and revenue potential of obesity medicine. 

Today marks a very different era.

Obesity medicine is exploding. Patients are spilling into doctors’ offices looking for obesity treatment. Healthcare systems are seeking out obesity specialists and building metabolic health centers. Since 2020, the number of doctors board-certified by the American Board of Obesity Medicine has nearly doubled, and the number of obesity medicine fellowships across the country has more than doubled. Next month, another 2115 doctors from primary care, surgery, orthopedics, pediatrics, fertility, endocrinology, and beyond will sit for the 2024 exam. The once niche specialty is quickly becoming intertwined with most of modern medicine.
 

The Need to Treat

It’s no mystery that the rapid expansion of obesity medicine coincides with the US Food and Drug Administration’s approval of GLP-1 injections. The drugs’ radical weight loss properties have captured headlines and driven up patient demand. Meanwhile, doctors are finally able to offer effective treatment for a disease that affects 40% of US adults.

“We are finally treating it as a chronic disease, not as a lifestyle,” said Marcio Griebeler, MD, director of the obesity medicine fellowship at the Cleveland Clinic. And “I think it’s fulfilling for physicians,” he said. 

For so long, the advice for obesity was about lifestyle. Move more, eat less, and harness willpower, “which really is a fallacy,” said Kimberly Gudzune, MD, MPH, an obesity medicine specialist and chief medical officer for the American Board of Obesity Medicine (ABOM) Foundation. For people with obesity, “your brain is operating differently,” she said. “Your body really is set up to work against you.” 

Brianna Johnson-Rabbett, MD, medical director of the ABOM, told this news organization that with the advent of GLP-1s, “there’s a clearer recognition that obesity is a disease that needs to be treated like other diseases.” Some of that is thanks to clinical trial data showing that just as with other diseases such as high blood pressure or diabetes, obesity can be treated with medication and it resurges when the medication is stopped, she said.

Doctors don’t have to go looking for patients with obesity, dr. Griebeler added. Now that treatment options exist, they’re showing up in droves at the doctor’s office — all the doctors’ offices. In primary care, endocrinology, surgery, pediatrics — a wide variety of doctors are being asked about obesity drugs, Dr. Griebeler noted.

And while doctors are often just as excited as patients about the potential for treatment, many find themselves under-equipped when it comes to obesity. “More physicians are ... recognizing the value in treating this, and some are realizing, “Oh gosh, I never learned how to do this,” said Dr. Gudzune.
 

Information Patients Have Been Waiting For

Medical training has traditionally devoted minimal, if any, curriculum to obesity and metabolism. “To be honest, we didn’t really cover this at all in my training,” said Nina Paddu, MD, obesity medicine specialist at Maimonides Medical Center in New York City who finished her training only 2 years ago. “The guidance even in residency was ‘let’s send them to nutrition’ and ‘recommend exercising.’ ”

In addition to the medical education gap, until recently there was a “paucity of robust evidence,” Dr. Srivastava said. Leaders in the field wanted to establish standards and guidelines, but there wasn’t enough strong evidence on obesity and its treatments to build them, she said. 

Only in the last 5 years or so has the evidence-based understanding of obesity’s pathophysiology truly accelerated: The brain’s driving roles, its interplay with hormones, and its interactions with other diseases. “We are just at the cusp of understanding all the different factors,” Dr. Gudzune said.

But already endocrinologists, surgeons, fertility specialists, gynecologists, and oncologists, to name a few, see the critical overlap with their own field. “Conditions were once suspected of being intertwined [with obesity], and now we have data to connect them,” Dr. Srivastava said. For example, there’s now data connecting semaglutide to a 20% reduction in cardiovascular events for people with obesity. That’s a game changer for multiple specialties, she told this news organization. 
 

Getting Trained in Obesity Management

The recent uptick in obesity insights and increased patient need has doctors from every career stage seeking additional training.

The ABOM offers two board certification pathways: 60 hours of CME credits or a 12-month fellowship. Both paths require doctors to pass the board’s exam. 

Many doctors incorporate the training into their existing practice. The CME credit pathway, especially, is designed to help get doctors up to speed without requiring them to upend their lives for a fellowship.

Dr. Srivastava said that the fellowship is more consuming and immersive. While it’s often younger doctors just out of training who apply to fellowship, every year, “I’m astonished at the number of talented physicians with clinical and research experience who want to immerse themselves in a fellowship experience.”

Some doctors return to their previous specialties after fellowship. But many will go on to take obesity medicine–specific roles or set aside clinic hours for obesity medicine. Their credentials are “really attractive to institutions, especially those looking to open up obesity medicine or weight management programs,” said Dr. Srivastava.

Dr. Paddu, who finished her obesity medicine fellowship this year, said there are a variety of obesity medicine jobs to choose from — far different from Dr. Srivastava’s job search 15 years ago. Dr. Paddu’s new role combines 2 days of primary care with 2 days devoted to obesity medicine and 1 day each week set aside for administrative work so she can build up the hospital’s new metabolic health clinic. 
 

Still Not Enough Obesity Specialists

As with all things, rapid growth requires careful oversight. “Part of the responsibility of the board is to think critically of how the field is growing” and conduct ongoing monitoring, Dr. Gudzune said.

This is also why the board’s credentials are time-limited and must be recertified, Dr. Johnson-Rabbett added. 

But even with the rise in certified doctors and obesity medicine positions, the 8263 doctors certified by ABOM are only a tiny fraction of US physicians. As a result, there’s genuine likelihood that many patients seeking GLP-1s or other obesity treatment don’t yet have access to the holistic care they need. Plus, doctors may still not have obesity expertise within their networks.

“The field has grown rapidly, but it’s still such a small field relative to the patient need,” said Dr. Gudzune.
 

A version of this article appeared on Medscape.com.

Gitanjali Srivastava, MD, professor of medicine, pediatrics, and surgery, and medical director of obesity medicine at Vanderbilt University School of Medicine in Nashville, Tennessee, was nearly 10 years into practicing pediatric medicine when she graduated from the obesity medicine fellowship at Massachusetts General Hospital in Boston in 2013. “We were the very first sort of fellows to speak of then; there were no standards or curriculum,” she said.

Obesity was already epidemic, but stigma and bias were still pervasive in the medical community and within the public. After graduating, Dr. Srivastava spent months vying for a position with hospital CEOs. She traveled across the country explaining the specialty and its value, going into detail about the budget, business model, space requirement, and revenue potential of obesity medicine. 

Today marks a very different era.

Obesity medicine is exploding. Patients are spilling into doctors’ offices looking for obesity treatment. Healthcare systems are seeking out obesity specialists and building metabolic health centers. Since 2020, the number of doctors board-certified by the American Board of Obesity Medicine has nearly doubled, and the number of obesity medicine fellowships across the country has more than doubled. Next month, another 2115 doctors from primary care, surgery, orthopedics, pediatrics, fertility, endocrinology, and beyond will sit for the 2024 exam. The once niche specialty is quickly becoming intertwined with most of modern medicine.
 

The Need to Treat

It’s no mystery that the rapid expansion of obesity medicine coincides with the US Food and Drug Administration’s approval of GLP-1 injections. The drugs’ radical weight loss properties have captured headlines and driven up patient demand. Meanwhile, doctors are finally able to offer effective treatment for a disease that affects 40% of US adults.

“We are finally treating it as a chronic disease, not as a lifestyle,” said Marcio Griebeler, MD, director of the obesity medicine fellowship at the Cleveland Clinic. And “I think it’s fulfilling for physicians,” he said. 

For so long, the advice for obesity was about lifestyle. Move more, eat less, and harness willpower, “which really is a fallacy,” said Kimberly Gudzune, MD, MPH, an obesity medicine specialist and chief medical officer for the American Board of Obesity Medicine (ABOM) Foundation. For people with obesity, “your brain is operating differently,” she said. “Your body really is set up to work against you.” 

Brianna Johnson-Rabbett, MD, medical director of the ABOM, told this news organization that with the advent of GLP-1s, “there’s a clearer recognition that obesity is a disease that needs to be treated like other diseases.” Some of that is thanks to clinical trial data showing that just as with other diseases such as high blood pressure or diabetes, obesity can be treated with medication and it resurges when the medication is stopped, she said.

Doctors don’t have to go looking for patients with obesity, dr. Griebeler added. Now that treatment options exist, they’re showing up in droves at the doctor’s office — all the doctors’ offices. In primary care, endocrinology, surgery, pediatrics — a wide variety of doctors are being asked about obesity drugs, Dr. Griebeler noted.

And while doctors are often just as excited as patients about the potential for treatment, many find themselves under-equipped when it comes to obesity. “More physicians are ... recognizing the value in treating this, and some are realizing, “Oh gosh, I never learned how to do this,” said Dr. Gudzune.
 

Information Patients Have Been Waiting For

Medical training has traditionally devoted minimal, if any, curriculum to obesity and metabolism. “To be honest, we didn’t really cover this at all in my training,” said Nina Paddu, MD, obesity medicine specialist at Maimonides Medical Center in New York City who finished her training only 2 years ago. “The guidance even in residency was ‘let’s send them to nutrition’ and ‘recommend exercising.’ ”

In addition to the medical education gap, until recently there was a “paucity of robust evidence,” Dr. Srivastava said. Leaders in the field wanted to establish standards and guidelines, but there wasn’t enough strong evidence on obesity and its treatments to build them, she said. 

Only in the last 5 years or so has the evidence-based understanding of obesity’s pathophysiology truly accelerated: The brain’s driving roles, its interplay with hormones, and its interactions with other diseases. “We are just at the cusp of understanding all the different factors,” Dr. Gudzune said.

But already endocrinologists, surgeons, fertility specialists, gynecologists, and oncologists, to name a few, see the critical overlap with their own field. “Conditions were once suspected of being intertwined [with obesity], and now we have data to connect them,” Dr. Srivastava said. For example, there’s now data connecting semaglutide to a 20% reduction in cardiovascular events for people with obesity. That’s a game changer for multiple specialties, she told this news organization. 
 

Getting Trained in Obesity Management

The recent uptick in obesity insights and increased patient need has doctors from every career stage seeking additional training.

The ABOM offers two board certification pathways: 60 hours of CME credits or a 12-month fellowship. Both paths require doctors to pass the board’s exam. 

Many doctors incorporate the training into their existing practice. The CME credit pathway, especially, is designed to help get doctors up to speed without requiring them to upend their lives for a fellowship.

Dr. Srivastava said that the fellowship is more consuming and immersive. While it’s often younger doctors just out of training who apply to fellowship, every year, “I’m astonished at the number of talented physicians with clinical and research experience who want to immerse themselves in a fellowship experience.”

Some doctors return to their previous specialties after fellowship. But many will go on to take obesity medicine–specific roles or set aside clinic hours for obesity medicine. Their credentials are “really attractive to institutions, especially those looking to open up obesity medicine or weight management programs,” said Dr. Srivastava.

Dr. Paddu, who finished her obesity medicine fellowship this year, said there are a variety of obesity medicine jobs to choose from — far different from Dr. Srivastava’s job search 15 years ago. Dr. Paddu’s new role combines 2 days of primary care with 2 days devoted to obesity medicine and 1 day each week set aside for administrative work so she can build up the hospital’s new metabolic health clinic. 
 

Still Not Enough Obesity Specialists

As with all things, rapid growth requires careful oversight. “Part of the responsibility of the board is to think critically of how the field is growing” and conduct ongoing monitoring, Dr. Gudzune said.

This is also why the board’s credentials are time-limited and must be recertified, Dr. Johnson-Rabbett added. 

But even with the rise in certified doctors and obesity medicine positions, the 8263 doctors certified by ABOM are only a tiny fraction of US physicians. As a result, there’s genuine likelihood that many patients seeking GLP-1s or other obesity treatment don’t yet have access to the holistic care they need. Plus, doctors may still not have obesity expertise within their networks.

“The field has grown rapidly, but it’s still such a small field relative to the patient need,” said Dr. Gudzune.
 

A version of this article appeared on Medscape.com.

LONDON — Single-pill combinations that include three or four antihypertensive medications are the way forward for the management of patients with elevated blood pressure, according to experts evaluating the new approach.

This multidrug strategy — in which ultralow-dose triple combinations can be used as a starting treatment and four full-dose combinations can be used to treat resistant hypertension — has shown an impressive ability to lower blood pressure in several new studies.

But will it catch on as a routine treatment recommendation in current practice?

Studies of treatment strategies that involve an ultralow quarter dose of three drugs that lower blood pressure and then escalation to a half-dose triple combination and then to a full-dose triple combination, all given as a single pill, were presented at the European Society of Cardiology (ESC) Congress 2024. Another strategy presented involves a four-drug full-dose combination in patients with resistant hypertension.
 

Start With Low Doses of Three Drugs

The triple-combination pill contains telmisartan (an angiotensin blocker), amlodipine (a calcium channel blocker), and indapamide (a diuretic). The three medications are used at three doses: Quarter, half, and standard.

“The idea is to start treatment with a little bit of the three main drug classes instead of the full dose of one drug and then to increase the triple-combination doses as required to get to blood pressure goal,” said Anthony Rodgers, PhD, from the team at The George Institute for Global Health, Sydney, Australia, that is developing this triple-combination product.

“Using three different mechanisms right from the beginning covers all the bases and leads to improved blood pressure reduction while just using very small doses of each agent. This represents a completely new approach that could transform the management of hypertension,” he reported.

Single-pill triple-combination antihypertensive formulations exist already, but the component drugs are all at standard doses. Such combinations were designed to improve adherence in patients with hard-to-control blood pressure who need more than two full-dose medications, he explained.

“We are suggesting a completely different concept using much lower doses of the triple combination right from the beginning of treatment,” Dr. Rodgers explained. “Convenience and adherence will be an added advantage, but there’s more to it than that. It’s about combining the different mechanisms of three separate drug classes to get a better antihypertensive effect and being able to do this right from the start of treatment in patients with mildly elevated blood pressure, as well as those with higher levels.”

Proof-of-concept trials of this approach have been conducted, but no commercial low-dose triple-combination product has been available.

The George Institute is now developing such a product — through George Medicines, its commercial arm — with the aim of bringing the triple-combination pill to market in both high- and low-income countries. An approval submission has been filed in the United States.

Dr. Rodgers presented two studies that assessed the triple combination. One showed that the quarter dose reduced blood pressure significantly better than placebo in patients with mildly elevated blood pressure. The second showed that half and standard doses of the three medications were more effective at lowering blood pressure than three dual combinations at the same doses.
 

The VERONICA Trial

The triple combination was also assessed in the VERONICA study, which showed that among Black adults in Nigeria with uncontrolled hypertension, blood pressure was lower and control was better with the low-dose triple-combination pill than with standard care, and tolerability was good.

In VERONICA, recently published in JAMA, 300 patients with a mean baseline blood pressure of 151/97 mm Hg at home and 156/97 mm Hg in the clinic were randomly assigned to receive the triple-combination pill or standard care.

In the triple-combination group, patients started with the quarter-dose pill, then accelerated, as necessary, to the half-dose and standard-dose pills.

In the standard care group, patients started with amlodipine (5 mg), which was stepped up at monthly intervals so patients could achieve a target blood pressure < 140/90 mm Hg as follows: Amlodipine (5 mg) plus losartan (50 mg); then amlodipine (10 mg) plus losartan (100 mg); then amlodipine (10 mg), losartan (100 mg), plus hydrochlorothiazide (25 mg); and finally referral to a specialist if the target blood pressure was still not achieved.

At month 6, mean home systolic blood pressure was, on average, 31 mm Hg lower in the triple-combination group and 26 mm Hg lower in the standard care group (adjusted difference, −5.8 mm Hg; P < .001).

More patients in the triple-combination group than in the standard care group achieved clinic blood pressure control, defined as blood pressure < 140/90 mm Hg (82% vs 72%), and more patients achieved home blood pressure control, defined as blood pressure below 130/80 mm Hg (62% vs 28%).

No participants discontinued treatment due to adverse events, and adverse events of special interest were reported by just 2% and 3% patients in the triple-combination and standard care groups, respectively.

At month 6, however, more participants in the triple-combination group than in the standard care group had serum potassium levels < 3.5 mmol/L (34% vs 18%), although fewer participants in both the groups had potassium levels < 3.0 mmol/L (10% vs 5%).

Hypokalemia may be the consequence of low dietary potassium intake in Africa, and co-administration with potassium-enriched salt substitution should be evaluated, said Dike Ojji, MBBS, PhD, University of Abuja, Nigeria, who was the lead investigator of VERONICA.

“These findings have broad clinical and public health implications, given that improved hypertension control is a priority in Africa and globally. The results underscore the need for combination therapy to be the cornerstone of effective treatment regimens,” Dr. Ojji said.
 

Missed Targets

“It has taken a long time for the penny to drop as to why the existing antihypertensive treatment paradigm does not work so well,” Dr. Rodgers pointed out. “What tends to happen in clinical practice is that people start on one drug and blood pressure falls a bit, then no further action is taken. But this is not usually enough to get to target. With our approach of using three drugs at low doses straight away, we can often get the blood pressure controlled to target much more quickly with one tablet.”

Low doses of the triple-combination pill should also have a favorable adverse-effect profile and fewer drug interactions, as these issues are generally seen much more frequently with higher doses of drugs, he explained.

This low-dose triple-combination approach could help manage the current epidemic of hypertension and cardiometabolic disease, said Pam Taub, MD, director of preventive cardiology at UC San Diego Health System.

“We are in a new era of cardiometabolic disease, and one of the fundamental drivers of atherosclerotic cardiovascular disease is hypertension, which is prevalent in patients with diabetes, in those with obesity, and is a contributor to chronic kidney disease,” she said.

“We really need to be addressing hypertension very early to prevent this end-organ damage, but because hypertension tends to occur alongside multiple other comorbidities, patients are often on many different medications and are overwhelmed by the burden of polypharmacy.”

Dr. Taub described this triple-combination approach as “looking at hypertension treatment through a new lens.”

“We’ve always been taught to maximize the dose of one agent before we go to a new agent,” she said. “These studies are fundamentally challenging that paradigm. From a pathophysiological and mechanistic perspective, we are seeing that lower doses of different medications can really harness some unique synergistic mechanisms, which can be beneficial for patients.”

But not all experts are convinced that this approach will be a popular option in all countries.

Although this approach makes sense, in that the different agents work synergistically to give a better antihypertensive effect, many physicians could be uncomfortable with the idea of giving multiple medications straight off as the first step of treatment, said Eugene Yang, MD, from the University of Washington in Seattle.

If the patient develops a side effect, it will not be clear which medication is causing it, making it difficult to know which one to stop, he pointed out.

“These studies confirm that a low-dose multidrug-combination pill is effective at lowering blood pressure, but we already have previous studies showing this,” he added. “The issue is how we translate this into patient care. It would be great if we could get people to use it, but I think concerns from both clinicians and patients about identifying the source of any side effects may be a stumbling block.”

The approach is more likely to be adopted in low- to middle-income countries, where there is limited access to healthcare and where the population-wide control of blood pressure makes sense, said Dr. Yang.

Most current guidelines now recommend initiating therapy with two agents, ideally, as a single-pill combination product. “We have finally acknowledged that the vast majority of patients need two drugs. That’s a good starting point. This low-dose triple combination could be an interesting new approach,” said Neil Poulter, MD, professor of preventive cardiovascular medicine at Imperial College London, England.

This approach is in line with the idea that single-pill combinations are the way forward for hypertension therapy, he added.

“The triple combination is attractive, in that you are never quite sure which particular mechanism is driving an individual’s elevated blood pressure, so if you can target three different mechanisms at the same time, you’ve got more chance of a good hit,” Dr. Poulter said.

“The VERONICA trial showed a very good result on lowering BP using this low-dose triple combination as a starting point and increasing quickly to single-pill combinations of triple half doses, then triple full doses, as required. But I think we need more evidence on how this compares to current practice than just this one study in Africa to make this an acceptable routine approach on a global level,” he said.
 

QUADRO: Four-Drug Combo in Resistant Hypertension

Another scenario in which single-pill antihypertensive combinations could be particularly useful is at the other end of the spectrum: The treatment of patients with resistant hypertension.

The QUADRO study showed that a single pill containing perindopril, indapamide, amlodipine, and bisoprolol is better at lowering blood pressure than the triple combination of perindopril, indapamide, and amlodipine.

The primary endpoint — office sitting systolic blood pressure at 16 weeks — was 8 mm Hg lower with the quadruple combination than with the triple combination. And mean ambulatory 24-hour systolic blood pressure was 7.5 mm Hg lower with the four-drug combination.

This was the first study of a single-pill quadruple combination in patients with resistant hypertension, which is a “difficult-to-treat condition demanding a high number of pills with not enough safe and practical options,” said Stefano Taddei, MD, from the University of Pisa, Italy, when he presented the study at the ESC meeting.

Using “four well-established drugs in a single-combination pill may improve adherence and should be an innovative solution for resistant and difficult-to-treat hypertensive patients,” he said.

Nonadherence is a big problem in patients with resistant hypertension. “It is really difficult to get patients to take three or four antihypertensive agents along with all the other medications they have for other comorbidities,” Dr. Taub pointed out. “We really need to think about combination formulations that reduce the pill burden for our patients.”

Around 10% patients with hypertension may require a fourth drug, so a four-drug single-pill combination therefore makes good sense, said Dr. Poulter.

But the choice of the fourth drug is the subject of debate. The PATHWAY trial showed spironolactone to be the most effective fourth agent, but it can cause side effects, such as gynecomastia and hyperkalemia.

“The beta-blocker in the four-drug combination product used in the QUADRO study may not be as effective as spironolactone at lowering blood pressure,” Dr. Poulter explained, noting that beta-blockers have known side effects. However, “they are often already recommended for patients with very common comorbidities, such as arrhythmias, history of MI, heart failure, angina. In that regard, it makes sense to have a beta-blocker in there.”

The four-drug combination used in the QUADRO study led to a bigger reduction — by 8 mm Hg — than the three-drug combination. “That’s pretty good. I thought this was a very useful and interesting study,” he said.

There could be a role for a four-drug combination product in resistant hypertension. “Whatever we can do to improve adherence and reduce blood pressure is good thing,” said Dr. Yang.

However, a mineralocorticoid receptor antagonist (such as spironolactone) might be better as the fourth drug; that is what is recommended in the resistant hypertension algorithm.
 

Lower Blood Pressure, Better Outcomes

“What we are seeing in these trials is that across a wide spectrum of patients with hypertension or resistant hypertension, combination pills are superior to standard practice for BP lowering, and that will lead to improved outcomes,” said Dr. Taub.

“For years, such single-pill combinations have been viewed as ‘bad medicine’ in hypertension,” Dr. Poulter added. “That is clearly not the case, as these studies are showing. And single-pill combination therapies are used extensively in practically every other area of medicine. We are starting to accept them now in the blood pressure community, and I think the use of triple and quadruple combinations, as in these studies, has a real logic to it. But for this approach to be useful, these single-pill combinations must be made available, cheaply, across the world, especially in low- and middle-income countries where hypertension rates are a particular problem.”
 

A version of this article appeared on Medscape.com.

LONDON — Single-pill combinations that include three or four antihypertensive medications are the way forward for the management of patients with elevated blood pressure, according to experts evaluating the new approach.

This multidrug strategy — in which ultralow-dose triple combinations can be used as a starting treatment and four full-dose combinations can be used to treat resistant hypertension — has shown an impressive ability to lower blood pressure in several new studies.

But will it catch on as a routine treatment recommendation in current practice?

Studies of treatment strategies that involve an ultralow quarter dose of three drugs that lower blood pressure and then escalation to a half-dose triple combination and then to a full-dose triple combination, all given as a single pill, were presented at the European Society of Cardiology (ESC) Congress 2024. Another strategy presented involves a four-drug full-dose combination in patients with resistant hypertension.
 

Start With Low Doses of Three Drugs

The triple-combination pill contains telmisartan (an angiotensin blocker), amlodipine (a calcium channel blocker), and indapamide (a diuretic). The three medications are used at three doses: Quarter, half, and standard.

“The idea is to start treatment with a little bit of the three main drug classes instead of the full dose of one drug and then to increase the triple-combination doses as required to get to blood pressure goal,” said Anthony Rodgers, PhD, from the team at The George Institute for Global Health, Sydney, Australia, that is developing this triple-combination product.

“Using three different mechanisms right from the beginning covers all the bases and leads to improved blood pressure reduction while just using very small doses of each agent. This represents a completely new approach that could transform the management of hypertension,” he reported.

Single-pill triple-combination antihypertensive formulations exist already, but the component drugs are all at standard doses. Such combinations were designed to improve adherence in patients with hard-to-control blood pressure who need more than two full-dose medications, he explained.

“We are suggesting a completely different concept using much lower doses of the triple combination right from the beginning of treatment,” Dr. Rodgers explained. “Convenience and adherence will be an added advantage, but there’s more to it than that. It’s about combining the different mechanisms of three separate drug classes to get a better antihypertensive effect and being able to do this right from the start of treatment in patients with mildly elevated blood pressure, as well as those with higher levels.”

Proof-of-concept trials of this approach have been conducted, but no commercial low-dose triple-combination product has been available.

The George Institute is now developing such a product — through George Medicines, its commercial arm — with the aim of bringing the triple-combination pill to market in both high- and low-income countries. An approval submission has been filed in the United States.

Dr. Rodgers presented two studies that assessed the triple combination. One showed that the quarter dose reduced blood pressure significantly better than placebo in patients with mildly elevated blood pressure. The second showed that half and standard doses of the three medications were more effective at lowering blood pressure than three dual combinations at the same doses.
 

The VERONICA Trial

The triple combination was also assessed in the VERONICA study, which showed that among Black adults in Nigeria with uncontrolled hypertension, blood pressure was lower and control was better with the low-dose triple-combination pill than with standard care, and tolerability was good.

In VERONICA, recently published in JAMA, 300 patients with a mean baseline blood pressure of 151/97 mm Hg at home and 156/97 mm Hg in the clinic were randomly assigned to receive the triple-combination pill or standard care.

In the triple-combination group, patients started with the quarter-dose pill, then accelerated, as necessary, to the half-dose and standard-dose pills.

In the standard care group, patients started with amlodipine (5 mg), which was stepped up at monthly intervals so patients could achieve a target blood pressure < 140/90 mm Hg as follows: Amlodipine (5 mg) plus losartan (50 mg); then amlodipine (10 mg) plus losartan (100 mg); then amlodipine (10 mg), losartan (100 mg), plus hydrochlorothiazide (25 mg); and finally referral to a specialist if the target blood pressure was still not achieved.

At month 6, mean home systolic blood pressure was, on average, 31 mm Hg lower in the triple-combination group and 26 mm Hg lower in the standard care group (adjusted difference, −5.8 mm Hg; P < .001).

More patients in the triple-combination group than in the standard care group achieved clinic blood pressure control, defined as blood pressure < 140/90 mm Hg (82% vs 72%), and more patients achieved home blood pressure control, defined as blood pressure below 130/80 mm Hg (62% vs 28%).

No participants discontinued treatment due to adverse events, and adverse events of special interest were reported by just 2% and 3% patients in the triple-combination and standard care groups, respectively.

At month 6, however, more participants in the triple-combination group than in the standard care group had serum potassium levels < 3.5 mmol/L (34% vs 18%), although fewer participants in both the groups had potassium levels < 3.0 mmol/L (10% vs 5%).

Hypokalemia may be the consequence of low dietary potassium intake in Africa, and co-administration with potassium-enriched salt substitution should be evaluated, said Dike Ojji, MBBS, PhD, University of Abuja, Nigeria, who was the lead investigator of VERONICA.

“These findings have broad clinical and public health implications, given that improved hypertension control is a priority in Africa and globally. The results underscore the need for combination therapy to be the cornerstone of effective treatment regimens,” Dr. Ojji said.
 

Missed Targets

“It has taken a long time for the penny to drop as to why the existing antihypertensive treatment paradigm does not work so well,” Dr. Rodgers pointed out. “What tends to happen in clinical practice is that people start on one drug and blood pressure falls a bit, then no further action is taken. But this is not usually enough to get to target. With our approach of using three drugs at low doses straight away, we can often get the blood pressure controlled to target much more quickly with one tablet.”

Low doses of the triple-combination pill should also have a favorable adverse-effect profile and fewer drug interactions, as these issues are generally seen much more frequently with higher doses of drugs, he explained.

This low-dose triple-combination approach could help manage the current epidemic of hypertension and cardiometabolic disease, said Pam Taub, MD, director of preventive cardiology at UC San Diego Health System.

“We are in a new era of cardiometabolic disease, and one of the fundamental drivers of atherosclerotic cardiovascular disease is hypertension, which is prevalent in patients with diabetes, in those with obesity, and is a contributor to chronic kidney disease,” she said.

“We really need to be addressing hypertension very early to prevent this end-organ damage, but because hypertension tends to occur alongside multiple other comorbidities, patients are often on many different medications and are overwhelmed by the burden of polypharmacy.”

Dr. Taub described this triple-combination approach as “looking at hypertension treatment through a new lens.”

“We’ve always been taught to maximize the dose of one agent before we go to a new agent,” she said. “These studies are fundamentally challenging that paradigm. From a pathophysiological and mechanistic perspective, we are seeing that lower doses of different medications can really harness some unique synergistic mechanisms, which can be beneficial for patients.”

But not all experts are convinced that this approach will be a popular option in all countries.

Although this approach makes sense, in that the different agents work synergistically to give a better antihypertensive effect, many physicians could be uncomfortable with the idea of giving multiple medications straight off as the first step of treatment, said Eugene Yang, MD, from the University of Washington in Seattle.

If the patient develops a side effect, it will not be clear which medication is causing it, making it difficult to know which one to stop, he pointed out.

“These studies confirm that a low-dose multidrug-combination pill is effective at lowering blood pressure, but we already have previous studies showing this,” he added. “The issue is how we translate this into patient care. It would be great if we could get people to use it, but I think concerns from both clinicians and patients about identifying the source of any side effects may be a stumbling block.”

The approach is more likely to be adopted in low- to middle-income countries, where there is limited access to healthcare and where the population-wide control of blood pressure makes sense, said Dr. Yang.

Most current guidelines now recommend initiating therapy with two agents, ideally, as a single-pill combination product. “We have finally acknowledged that the vast majority of patients need two drugs. That’s a good starting point. This low-dose triple combination could be an interesting new approach,” said Neil Poulter, MD, professor of preventive cardiovascular medicine at Imperial College London, England.

This approach is in line with the idea that single-pill combinations are the way forward for hypertension therapy, he added.

“The triple combination is attractive, in that you are never quite sure which particular mechanism is driving an individual’s elevated blood pressure, so if you can target three different mechanisms at the same time, you’ve got more chance of a good hit,” Dr. Poulter said.

“The VERONICA trial showed a very good result on lowering BP using this low-dose triple combination as a starting point and increasing quickly to single-pill combinations of triple half doses, then triple full doses, as required. But I think we need more evidence on how this compares to current practice than just this one study in Africa to make this an acceptable routine approach on a global level,” he said.
 

QUADRO: Four-Drug Combo in Resistant Hypertension

Another scenario in which single-pill antihypertensive combinations could be particularly useful is at the other end of the spectrum: The treatment of patients with resistant hypertension.

The QUADRO study showed that a single pill containing perindopril, indapamide, amlodipine, and bisoprolol is better at lowering blood pressure than the triple combination of perindopril, indapamide, and amlodipine.

The primary endpoint — office sitting systolic blood pressure at 16 weeks — was 8 mm Hg lower with the quadruple combination than with the triple combination. And mean ambulatory 24-hour systolic blood pressure was 7.5 mm Hg lower with the four-drug combination.

This was the first study of a single-pill quadruple combination in patients with resistant hypertension, which is a “difficult-to-treat condition demanding a high number of pills with not enough safe and practical options,” said Stefano Taddei, MD, from the University of Pisa, Italy, when he presented the study at the ESC meeting.

Using “four well-established drugs in a single-combination pill may improve adherence and should be an innovative solution for resistant and difficult-to-treat hypertensive patients,” he said.

Nonadherence is a big problem in patients with resistant hypertension. “It is really difficult to get patients to take three or four antihypertensive agents along with all the other medications they have for other comorbidities,” Dr. Taub pointed out. “We really need to think about combination formulations that reduce the pill burden for our patients.”

Around 10% patients with hypertension may require a fourth drug, so a four-drug single-pill combination therefore makes good sense, said Dr. Poulter.

But the choice of the fourth drug is the subject of debate. The PATHWAY trial showed spironolactone to be the most effective fourth agent, but it can cause side effects, such as gynecomastia and hyperkalemia.

“The beta-blocker in the four-drug combination product used in the QUADRO study may not be as effective as spironolactone at lowering blood pressure,” Dr. Poulter explained, noting that beta-blockers have known side effects. However, “they are often already recommended for patients with very common comorbidities, such as arrhythmias, history of MI, heart failure, angina. In that regard, it makes sense to have a beta-blocker in there.”

The four-drug combination used in the QUADRO study led to a bigger reduction — by 8 mm Hg — than the three-drug combination. “That’s pretty good. I thought this was a very useful and interesting study,” he said.

There could be a role for a four-drug combination product in resistant hypertension. “Whatever we can do to improve adherence and reduce blood pressure is good thing,” said Dr. Yang.

However, a mineralocorticoid receptor antagonist (such as spironolactone) might be better as the fourth drug; that is what is recommended in the resistant hypertension algorithm.
 

Lower Blood Pressure, Better Outcomes

“What we are seeing in these trials is that across a wide spectrum of patients with hypertension or resistant hypertension, combination pills are superior to standard practice for BP lowering, and that will lead to improved outcomes,” said Dr. Taub.

“For years, such single-pill combinations have been viewed as ‘bad medicine’ in hypertension,” Dr. Poulter added. “That is clearly not the case, as these studies are showing. And single-pill combination therapies are used extensively in practically every other area of medicine. We are starting to accept them now in the blood pressure community, and I think the use of triple and quadruple combinations, as in these studies, has a real logic to it. But for this approach to be useful, these single-pill combinations must be made available, cheaply, across the world, especially in low- and middle-income countries where hypertension rates are a particular problem.”
 

A version of this article appeared on Medscape.com.

LONDON — Single-pill combinations that include three or four antihypertensive medications are the way forward for the management of patients with elevated blood pressure, according to experts evaluating the new approach.

This multidrug strategy — in which ultralow-dose triple combinations can be used as a starting treatment and four full-dose combinations can be used to treat resistant hypertension — has shown an impressive ability to lower blood pressure in several new studies.

But will it catch on as a routine treatment recommendation in current practice?

Studies of treatment strategies that involve an ultralow quarter dose of three drugs that lower blood pressure and then escalation to a half-dose triple combination and then to a full-dose triple combination, all given as a single pill, were presented at the European Society of Cardiology (ESC) Congress 2024. Another strategy presented involves a four-drug full-dose combination in patients with resistant hypertension.
 

Start With Low Doses of Three Drugs

The triple-combination pill contains telmisartan (an angiotensin blocker), amlodipine (a calcium channel blocker), and indapamide (a diuretic). The three medications are used at three doses: Quarter, half, and standard.

“The idea is to start treatment with a little bit of the three main drug classes instead of the full dose of one drug and then to increase the triple-combination doses as required to get to blood pressure goal,” said Anthony Rodgers, PhD, from the team at The George Institute for Global Health, Sydney, Australia, that is developing this triple-combination product.

“Using three different mechanisms right from the beginning covers all the bases and leads to improved blood pressure reduction while just using very small doses of each agent. This represents a completely new approach that could transform the management of hypertension,” he reported.

Single-pill triple-combination antihypertensive formulations exist already, but the component drugs are all at standard doses. Such combinations were designed to improve adherence in patients with hard-to-control blood pressure who need more than two full-dose medications, he explained.

“We are suggesting a completely different concept using much lower doses of the triple combination right from the beginning of treatment,” Dr. Rodgers explained. “Convenience and adherence will be an added advantage, but there’s more to it than that. It’s about combining the different mechanisms of three separate drug classes to get a better antihypertensive effect and being able to do this right from the start of treatment in patients with mildly elevated blood pressure, as well as those with higher levels.”

Proof-of-concept trials of this approach have been conducted, but no commercial low-dose triple-combination product has been available.

The George Institute is now developing such a product — through George Medicines, its commercial arm — with the aim of bringing the triple-combination pill to market in both high- and low-income countries. An approval submission has been filed in the United States.

Dr. Rodgers presented two studies that assessed the triple combination. One showed that the quarter dose reduced blood pressure significantly better than placebo in patients with mildly elevated blood pressure. The second showed that half and standard doses of the three medications were more effective at lowering blood pressure than three dual combinations at the same doses.
 

The VERONICA Trial

The triple combination was also assessed in the VERONICA study, which showed that among Black adults in Nigeria with uncontrolled hypertension, blood pressure was lower and control was better with the low-dose triple-combination pill than with standard care, and tolerability was good.

In VERONICA, recently published in JAMA, 300 patients with a mean baseline blood pressure of 151/97 mm Hg at home and 156/97 mm Hg in the clinic were randomly assigned to receive the triple-combination pill or standard care.

In the triple-combination group, patients started with the quarter-dose pill, then accelerated, as necessary, to the half-dose and standard-dose pills.

In the standard care group, patients started with amlodipine (5 mg), which was stepped up at monthly intervals so patients could achieve a target blood pressure < 140/90 mm Hg as follows: Amlodipine (5 mg) plus losartan (50 mg); then amlodipine (10 mg) plus losartan (100 mg); then amlodipine (10 mg), losartan (100 mg), plus hydrochlorothiazide (25 mg); and finally referral to a specialist if the target blood pressure was still not achieved.

At month 6, mean home systolic blood pressure was, on average, 31 mm Hg lower in the triple-combination group and 26 mm Hg lower in the standard care group (adjusted difference, −5.8 mm Hg; P < .001).

More patients in the triple-combination group than in the standard care group achieved clinic blood pressure control, defined as blood pressure < 140/90 mm Hg (82% vs 72%), and more patients achieved home blood pressure control, defined as blood pressure below 130/80 mm Hg (62% vs 28%).

No participants discontinued treatment due to adverse events, and adverse events of special interest were reported by just 2% and 3% patients in the triple-combination and standard care groups, respectively.

At month 6, however, more participants in the triple-combination group than in the standard care group had serum potassium levels < 3.5 mmol/L (34% vs 18%), although fewer participants in both the groups had potassium levels < 3.0 mmol/L (10% vs 5%).

Hypokalemia may be the consequence of low dietary potassium intake in Africa, and co-administration with potassium-enriched salt substitution should be evaluated, said Dike Ojji, MBBS, PhD, University of Abuja, Nigeria, who was the lead investigator of VERONICA.

“These findings have broad clinical and public health implications, given that improved hypertension control is a priority in Africa and globally. The results underscore the need for combination therapy to be the cornerstone of effective treatment regimens,” Dr. Ojji said.
 

Missed Targets

“It has taken a long time for the penny to drop as to why the existing antihypertensive treatment paradigm does not work so well,” Dr. Rodgers pointed out. “What tends to happen in clinical practice is that people start on one drug and blood pressure falls a bit, then no further action is taken. But this is not usually enough to get to target. With our approach of using three drugs at low doses straight away, we can often get the blood pressure controlled to target much more quickly with one tablet.”

Low doses of the triple-combination pill should also have a favorable adverse-effect profile and fewer drug interactions, as these issues are generally seen much more frequently with higher doses of drugs, he explained.

This low-dose triple-combination approach could help manage the current epidemic of hypertension and cardiometabolic disease, said Pam Taub, MD, director of preventive cardiology at UC San Diego Health System.

“We are in a new era of cardiometabolic disease, and one of the fundamental drivers of atherosclerotic cardiovascular disease is hypertension, which is prevalent in patients with diabetes, in those with obesity, and is a contributor to chronic kidney disease,” she said.

“We really need to be addressing hypertension very early to prevent this end-organ damage, but because hypertension tends to occur alongside multiple other comorbidities, patients are often on many different medications and are overwhelmed by the burden of polypharmacy.”

Dr. Taub described this triple-combination approach as “looking at hypertension treatment through a new lens.”

“We’ve always been taught to maximize the dose of one agent before we go to a new agent,” she said. “These studies are fundamentally challenging that paradigm. From a pathophysiological and mechanistic perspective, we are seeing that lower doses of different medications can really harness some unique synergistic mechanisms, which can be beneficial for patients.”

But not all experts are convinced that this approach will be a popular option in all countries.

Although this approach makes sense, in that the different agents work synergistically to give a better antihypertensive effect, many physicians could be uncomfortable with the idea of giving multiple medications straight off as the first step of treatment, said Eugene Yang, MD, from the University of Washington in Seattle.

If the patient develops a side effect, it will not be clear which medication is causing it, making it difficult to know which one to stop, he pointed out.

“These studies confirm that a low-dose multidrug-combination pill is effective at lowering blood pressure, but we already have previous studies showing this,” he added. “The issue is how we translate this into patient care. It would be great if we could get people to use it, but I think concerns from both clinicians and patients about identifying the source of any side effects may be a stumbling block.”

The approach is more likely to be adopted in low- to middle-income countries, where there is limited access to healthcare and where the population-wide control of blood pressure makes sense, said Dr. Yang.

Most current guidelines now recommend initiating therapy with two agents, ideally, as a single-pill combination product. “We have finally acknowledged that the vast majority of patients need two drugs. That’s a good starting point. This low-dose triple combination could be an interesting new approach,” said Neil Poulter, MD, professor of preventive cardiovascular medicine at Imperial College London, England.

This approach is in line with the idea that single-pill combinations are the way forward for hypertension therapy, he added.

“The triple combination is attractive, in that you are never quite sure which particular mechanism is driving an individual’s elevated blood pressure, so if you can target three different mechanisms at the same time, you’ve got more chance of a good hit,” Dr. Poulter said.

“The VERONICA trial showed a very good result on lowering BP using this low-dose triple combination as a starting point and increasing quickly to single-pill combinations of triple half doses, then triple full doses, as required. But I think we need more evidence on how this compares to current practice than just this one study in Africa to make this an acceptable routine approach on a global level,” he said.
 

QUADRO: Four-Drug Combo in Resistant Hypertension

Another scenario in which single-pill antihypertensive combinations could be particularly useful is at the other end of the spectrum: The treatment of patients with resistant hypertension.

The QUADRO study showed that a single pill containing perindopril, indapamide, amlodipine, and bisoprolol is better at lowering blood pressure than the triple combination of perindopril, indapamide, and amlodipine.

The primary endpoint — office sitting systolic blood pressure at 16 weeks — was 8 mm Hg lower with the quadruple combination than with the triple combination. And mean ambulatory 24-hour systolic blood pressure was 7.5 mm Hg lower with the four-drug combination.

This was the first study of a single-pill quadruple combination in patients with resistant hypertension, which is a “difficult-to-treat condition demanding a high number of pills with not enough safe and practical options,” said Stefano Taddei, MD, from the University of Pisa, Italy, when he presented the study at the ESC meeting.

Using “four well-established drugs in a single-combination pill may improve adherence and should be an innovative solution for resistant and difficult-to-treat hypertensive patients,” he said.

Nonadherence is a big problem in patients with resistant hypertension. “It is really difficult to get patients to take three or four antihypertensive agents along with all the other medications they have for other comorbidities,” Dr. Taub pointed out. “We really need to think about combination formulations that reduce the pill burden for our patients.”

Around 10% patients with hypertension may require a fourth drug, so a four-drug single-pill combination therefore makes good sense, said Dr. Poulter.

But the choice of the fourth drug is the subject of debate. The PATHWAY trial showed spironolactone to be the most effective fourth agent, but it can cause side effects, such as gynecomastia and hyperkalemia.

“The beta-blocker in the four-drug combination product used in the QUADRO study may not be as effective as spironolactone at lowering blood pressure,” Dr. Poulter explained, noting that beta-blockers have known side effects. However, “they are often already recommended for patients with very common comorbidities, such as arrhythmias, history of MI, heart failure, angina. In that regard, it makes sense to have a beta-blocker in there.”

The four-drug combination used in the QUADRO study led to a bigger reduction — by 8 mm Hg — than the three-drug combination. “That’s pretty good. I thought this was a very useful and interesting study,” he said.

There could be a role for a four-drug combination product in resistant hypertension. “Whatever we can do to improve adherence and reduce blood pressure is good thing,” said Dr. Yang.

However, a mineralocorticoid receptor antagonist (such as spironolactone) might be better as the fourth drug; that is what is recommended in the resistant hypertension algorithm.
 

Lower Blood Pressure, Better Outcomes

“What we are seeing in these trials is that across a wide spectrum of patients with hypertension or resistant hypertension, combination pills are superior to standard practice for BP lowering, and that will lead to improved outcomes,” said Dr. Taub.

“For years, such single-pill combinations have been viewed as ‘bad medicine’ in hypertension,” Dr. Poulter added. “That is clearly not the case, as these studies are showing. And single-pill combination therapies are used extensively in practically every other area of medicine. We are starting to accept them now in the blood pressure community, and I think the use of triple and quadruple combinations, as in these studies, has a real logic to it. But for this approach to be useful, these single-pill combinations must be made available, cheaply, across the world, especially in low- and middle-income countries where hypertension rates are a particular problem.”
 

A version of this article appeared on Medscape.com.

MILAN — Antidepressants escitalopram and duloxetine have been shown to improve verbal memory in moderate to severe depression, a clinical effect linked to changes in serotonin 4 (5-HT4) receptor levels in the brain, as shown on PET.

These findings suggested there is a role for specifically targeting the 5-HT4 receptor to improve verbal memory in depression, said investigator Vibeke H. Dam, PhD, from Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

“Verbal memory is often impaired in depression, and this has a lot of impact on patients’ ability to work and have a normal life. That’s why we’re so excited about this receptor in particular,” Dr. Dam said.

“If we can find a way to activate it more directly, we’re thinking this could be a way to treat this memory symptom that a lot of patients have and that currently we don’t really have a treatment for,” she added.

The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and recently published in Biological Psychiatry .
 

Largest Trial of Its Kind

The study is the largest single-site PET trial investigating serotonergic neurotransmission in major depressive disorder over the course of antidepressant treatment to date. It included 90 patients with moderate to severe depression who underwent baseline cognitive tests and brain scans to measure 5-HT4 receptor levels before starting their treatment with the selective serotonin reuptake inhibitor escitalopram.

Patients who showed no improvement in depressive symptoms after 4 weeks (n = 14), as assessed by the Hamilton Depression Rating Scale 6 (HAMD6), were switched to the serotonin-norepinephrine reuptake inhibitor duloxetine.

Both escitalopram and duloxetine inhibit the reuptake of 5-HT4, enhancing neurotransmitter activity; escitalopram primarily increases serotonin levels, while duloxetine increases both serotonin and norepinephrine levels.

The primary cognitive outcome measure was change in the Verbal Affective Memory Task 26. Secondary cognitive outcomes were change in working memory, reaction time, emotion recognition bias, and negative social emotion.

After 8 weeks of treatment, a subset of 40 patients repeated PET scans, and at 12 weeks, all patients repeated cognitive testing.

Matching neuroimaging and cognitive data were available for 88 patients at baseline and for 39 patients with rescan.

As expected, the study showed that antidepressant treatment resulted in the downregulation of 5-HT4 receptor levels. “One hypothesis is that if we increase the availability of serotonin [with treatment], downregulation of the receptors might be a response,” said Dr. Dam.

“What was interesting was that this was the effect across all patients, whether they [clinically] responded or not. So we see the medication does what it’s supposed to do in the brain.” But, she said, there was no association between 5-HT4 receptor levels and HAMD6 scores.
 

Gains in Verbal Memory

Although the downregulation of 5-HT4 did not correlate with somatic or mood symptoms, it did correlate with cognitive symptoms.

Interestingly, while most patients showed improvement in depressive symptoms — many reaching remission or recovery — they also experienced gains in verbal memory. However, these improvements were not correlated. It was possible for one to improve more than the other, with no apparent link between the two, said Dr. Dam.

“What was linked was how the brain responded to the medication for this particular receptor. So even though there is this downregulation of the receptor, there’s still a lot of activation of it, and our thinking is that it’s activation of the receptor that is the important bit.”

Work by other groups has shown that another medication, prucalopride, which is used to treat gastroparesis, can more directly activate the 5-HT4 receptor, and that the treatment of healthy volunteers with this medication can boost memory and learning, said Dr. Dam.

“We could repurpose this drug, and we’re currently looking for funding to test this in a wide variety of different groups such as concussion, diabetes, and depression.”

The study’s coinvestigator, Vibe G. Frokjaer, MD, said more research is required to understand the potential implications of the findings.

“Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression,” she said in a release.

Commenting on the research, Philip Cowen, MD, professor of psychopharmacology at the University of Oxford, England, said in a release that in light of “recent controversies about the role of brain serotonin in clinical depression, it is noteworthy that the PET studies of the Copenhagen Group provide unequivocal evidence that brain 5-HT4 receptors are decreased in unmedicated depressed patients.

“Their work also demonstrates the intimate role of brain 5-HT4 receptors in cognitive function,” he added. “This confirms recent work from Oxford, showing that the 5-HT4 receptor stimulant, prucalopride — a drug licensed for the treatment of constipation — improves memory in both healthy participants and people at risk of depression,” he added.

The study was funded by the Innovation Fund Denmark, Research Fund of the Mental Health Services – Capital Region of Denmark, Independent Research Fund Denmark, Global Justice Foundation, Research Council of Rigshospitalet, Augustinus Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Lundbeck Foundation, and H. Lundbeck A/S.

Dr. Dam reported serving as a speaker for H. Lundbeck. Frokjaer reported serving as a consultant for Sage Therapeutics and lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. Study investigator Martin B. Jørgensen has given talks sponsored by Boehringer Ingelheim and Lundbeck Pharma. All other investigators reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

MILAN — Antidepressants escitalopram and duloxetine have been shown to improve verbal memory in moderate to severe depression, a clinical effect linked to changes in serotonin 4 (5-HT4) receptor levels in the brain, as shown on PET.

These findings suggested there is a role for specifically targeting the 5-HT4 receptor to improve verbal memory in depression, said investigator Vibeke H. Dam, PhD, from Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

“Verbal memory is often impaired in depression, and this has a lot of impact on patients’ ability to work and have a normal life. That’s why we’re so excited about this receptor in particular,” Dr. Dam said.

“If we can find a way to activate it more directly, we’re thinking this could be a way to treat this memory symptom that a lot of patients have and that currently we don’t really have a treatment for,” she added.

The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and recently published in Biological Psychiatry .
 

Largest Trial of Its Kind

The study is the largest single-site PET trial investigating serotonergic neurotransmission in major depressive disorder over the course of antidepressant treatment to date. It included 90 patients with moderate to severe depression who underwent baseline cognitive tests and brain scans to measure 5-HT4 receptor levels before starting their treatment with the selective serotonin reuptake inhibitor escitalopram.

Patients who showed no improvement in depressive symptoms after 4 weeks (n = 14), as assessed by the Hamilton Depression Rating Scale 6 (HAMD6), were switched to the serotonin-norepinephrine reuptake inhibitor duloxetine.

Both escitalopram and duloxetine inhibit the reuptake of 5-HT4, enhancing neurotransmitter activity; escitalopram primarily increases serotonin levels, while duloxetine increases both serotonin and norepinephrine levels.

The primary cognitive outcome measure was change in the Verbal Affective Memory Task 26. Secondary cognitive outcomes were change in working memory, reaction time, emotion recognition bias, and negative social emotion.

After 8 weeks of treatment, a subset of 40 patients repeated PET scans, and at 12 weeks, all patients repeated cognitive testing.

Matching neuroimaging and cognitive data were available for 88 patients at baseline and for 39 patients with rescan.

As expected, the study showed that antidepressant treatment resulted in the downregulation of 5-HT4 receptor levels. “One hypothesis is that if we increase the availability of serotonin [with treatment], downregulation of the receptors might be a response,” said Dr. Dam.

“What was interesting was that this was the effect across all patients, whether they [clinically] responded or not. So we see the medication does what it’s supposed to do in the brain.” But, she said, there was no association between 5-HT4 receptor levels and HAMD6 scores.
 

Gains in Verbal Memory

Although the downregulation of 5-HT4 did not correlate with somatic or mood symptoms, it did correlate with cognitive symptoms.

Interestingly, while most patients showed improvement in depressive symptoms — many reaching remission or recovery — they also experienced gains in verbal memory. However, these improvements were not correlated. It was possible for one to improve more than the other, with no apparent link between the two, said Dr. Dam.

“What was linked was how the brain responded to the medication for this particular receptor. So even though there is this downregulation of the receptor, there’s still a lot of activation of it, and our thinking is that it’s activation of the receptor that is the important bit.”

Work by other groups has shown that another medication, prucalopride, which is used to treat gastroparesis, can more directly activate the 5-HT4 receptor, and that the treatment of healthy volunteers with this medication can boost memory and learning, said Dr. Dam.

“We could repurpose this drug, and we’re currently looking for funding to test this in a wide variety of different groups such as concussion, diabetes, and depression.”

The study’s coinvestigator, Vibe G. Frokjaer, MD, said more research is required to understand the potential implications of the findings.

“Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression,” she said in a release.

Commenting on the research, Philip Cowen, MD, professor of psychopharmacology at the University of Oxford, England, said in a release that in light of “recent controversies about the role of brain serotonin in clinical depression, it is noteworthy that the PET studies of the Copenhagen Group provide unequivocal evidence that brain 5-HT4 receptors are decreased in unmedicated depressed patients.

“Their work also demonstrates the intimate role of brain 5-HT4 receptors in cognitive function,” he added. “This confirms recent work from Oxford, showing that the 5-HT4 receptor stimulant, prucalopride — a drug licensed for the treatment of constipation — improves memory in both healthy participants and people at risk of depression,” he added.

The study was funded by the Innovation Fund Denmark, Research Fund of the Mental Health Services – Capital Region of Denmark, Independent Research Fund Denmark, Global Justice Foundation, Research Council of Rigshospitalet, Augustinus Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Lundbeck Foundation, and H. Lundbeck A/S.

Dr. Dam reported serving as a speaker for H. Lundbeck. Frokjaer reported serving as a consultant for Sage Therapeutics and lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. Study investigator Martin B. Jørgensen has given talks sponsored by Boehringer Ingelheim and Lundbeck Pharma. All other investigators reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

MILAN — Antidepressants escitalopram and duloxetine have been shown to improve verbal memory in moderate to severe depression, a clinical effect linked to changes in serotonin 4 (5-HT4) receptor levels in the brain, as shown on PET.

These findings suggested there is a role for specifically targeting the 5-HT4 receptor to improve verbal memory in depression, said investigator Vibeke H. Dam, PhD, from Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

“Verbal memory is often impaired in depression, and this has a lot of impact on patients’ ability to work and have a normal life. That’s why we’re so excited about this receptor in particular,” Dr. Dam said.

“If we can find a way to activate it more directly, we’re thinking this could be a way to treat this memory symptom that a lot of patients have and that currently we don’t really have a treatment for,” she added.

The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and recently published in Biological Psychiatry .
 

Largest Trial of Its Kind

The study is the largest single-site PET trial investigating serotonergic neurotransmission in major depressive disorder over the course of antidepressant treatment to date. It included 90 patients with moderate to severe depression who underwent baseline cognitive tests and brain scans to measure 5-HT4 receptor levels before starting their treatment with the selective serotonin reuptake inhibitor escitalopram.

Patients who showed no improvement in depressive symptoms after 4 weeks (n = 14), as assessed by the Hamilton Depression Rating Scale 6 (HAMD6), were switched to the serotonin-norepinephrine reuptake inhibitor duloxetine.

Both escitalopram and duloxetine inhibit the reuptake of 5-HT4, enhancing neurotransmitter activity; escitalopram primarily increases serotonin levels, while duloxetine increases both serotonin and norepinephrine levels.

The primary cognitive outcome measure was change in the Verbal Affective Memory Task 26. Secondary cognitive outcomes were change in working memory, reaction time, emotion recognition bias, and negative social emotion.

After 8 weeks of treatment, a subset of 40 patients repeated PET scans, and at 12 weeks, all patients repeated cognitive testing.

Matching neuroimaging and cognitive data were available for 88 patients at baseline and for 39 patients with rescan.

As expected, the study showed that antidepressant treatment resulted in the downregulation of 5-HT4 receptor levels. “One hypothesis is that if we increase the availability of serotonin [with treatment], downregulation of the receptors might be a response,” said Dr. Dam.

“What was interesting was that this was the effect across all patients, whether they [clinically] responded or not. So we see the medication does what it’s supposed to do in the brain.” But, she said, there was no association between 5-HT4 receptor levels and HAMD6 scores.
 

Gains in Verbal Memory

Although the downregulation of 5-HT4 did not correlate with somatic or mood symptoms, it did correlate with cognitive symptoms.

Interestingly, while most patients showed improvement in depressive symptoms — many reaching remission or recovery — they also experienced gains in verbal memory. However, these improvements were not correlated. It was possible for one to improve more than the other, with no apparent link between the two, said Dr. Dam.

“What was linked was how the brain responded to the medication for this particular receptor. So even though there is this downregulation of the receptor, there’s still a lot of activation of it, and our thinking is that it’s activation of the receptor that is the important bit.”

Work by other groups has shown that another medication, prucalopride, which is used to treat gastroparesis, can more directly activate the 5-HT4 receptor, and that the treatment of healthy volunteers with this medication can boost memory and learning, said Dr. Dam.

“We could repurpose this drug, and we’re currently looking for funding to test this in a wide variety of different groups such as concussion, diabetes, and depression.”

The study’s coinvestigator, Vibe G. Frokjaer, MD, said more research is required to understand the potential implications of the findings.

“Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression,” she said in a release.

Commenting on the research, Philip Cowen, MD, professor of psychopharmacology at the University of Oxford, England, said in a release that in light of “recent controversies about the role of brain serotonin in clinical depression, it is noteworthy that the PET studies of the Copenhagen Group provide unequivocal evidence that brain 5-HT4 receptors are decreased in unmedicated depressed patients.

“Their work also demonstrates the intimate role of brain 5-HT4 receptors in cognitive function,” he added. “This confirms recent work from Oxford, showing that the 5-HT4 receptor stimulant, prucalopride — a drug licensed for the treatment of constipation — improves memory in both healthy participants and people at risk of depression,” he added.

The study was funded by the Innovation Fund Denmark, Research Fund of the Mental Health Services – Capital Region of Denmark, Independent Research Fund Denmark, Global Justice Foundation, Research Council of Rigshospitalet, Augustinus Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Lundbeck Foundation, and H. Lundbeck A/S.

Dr. Dam reported serving as a speaker for H. Lundbeck. Frokjaer reported serving as a consultant for Sage Therapeutics and lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. Study investigator Martin B. Jørgensen has given talks sponsored by Boehringer Ingelheim and Lundbeck Pharma. All other investigators reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.