Family Practice News

TOPLINE:

Atherosclerotic cardiovascular disease (ASCVD) risk is higher with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) than with psoriasis.

METHODOLOGY:

• A retrospective matched longitudinal study compared the incidence and prevalence of ASCVD of 8138 individuals with CLE; 24,675 with SLE; 192,577 with psoriasis; and 81,380 control individuals.
• The disease-free control population was matched in a 10:1 ratio to the CLE population on the basis of age, sex, insurance type, and enrollment duration.
• Prevalent ASCVD was defined as coronary artery disease, prior myocardial infarction, or cerebrovascular accident, with ASCVD incidence assessed by number of hospitalizations over 3 years.

TAKEAWAY:

• Persons with CLE had higher ASCVD risk than control individuals (odds ratio [OR], 1.72; P < .001), similar to those with SLE (OR, 2.41; P < .001) but unlike those with psoriasis (OR, 1.03; P = .48).
• ASCVD incidence at 3 years was 24.8 per 1000 person-years for SLE, 15.2 per 1000 person-years for CLE, 14.0 per 1000 person-years for psoriasis, and 10.3 per 1000 person-years for controls.
• Multivariable Cox proportional regression modeling showed ASCVD risk was highest in those with SLE (hazard ratio [HR], 2.23; P < .001) vs CLE (HR, 1.32; P < .001) and psoriasis (HR, 1.06; P = .09).
• ASCVD prevalence was higher in individuals with CLE receiving systemic therapy (2.7%) than in those receiving no therapy (1.6%), suggesting a potential link between disease severity and CVD risk.

IN PRACTICE:

“Persons with CLE are at higher risk for ASCVD, and guidelines for the evaluation and management of ASCVD may improve their quality of care,” the authors wrote.

SOURCE:

The study was led by Henry W. Chen, MD, Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. It was published online on December 4, 2024, in JAMA Dermatology.

LIMITATIONS: 

The study was limited by its relatively young population (median age, 49 years) and the exclusion of adults aged > 65 years on Medicare insurance plans. The database lacked race and ethnicity data, and the analysis was restricted to a shorter 3-year period. The study could not fully evaluate detailed risk factors such as blood pressure levels, cholesterol measurements, or glycemic control, nor could it accurately assess smoking status.

DISCLOSURES:

The research was supported by the Department of Dermatology at the University of Texas Southwestern Medical Center and a grant from the National Institutes of Health. Several authors reported receiving grants or personal fees from various pharmaceutical companies. One author reported being a deputy editor for diversity, equity, and inclusion at JAMA Cardiology. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Atherosclerotic cardiovascular disease (ASCVD) risk is higher with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) than with psoriasis.

METHODOLOGY:

• A retrospective matched longitudinal study compared the incidence and prevalence of ASCVD of 8138 individuals with CLE; 24,675 with SLE; 192,577 with psoriasis; and 81,380 control individuals.
• The disease-free control population was matched in a 10:1 ratio to the CLE population on the basis of age, sex, insurance type, and enrollment duration.
• Prevalent ASCVD was defined as coronary artery disease, prior myocardial infarction, or cerebrovascular accident, with ASCVD incidence assessed by number of hospitalizations over 3 years.

TAKEAWAY:

• Persons with CLE had higher ASCVD risk than control individuals (odds ratio [OR], 1.72; P < .001), similar to those with SLE (OR, 2.41; P < .001) but unlike those with psoriasis (OR, 1.03; P = .48).
• ASCVD incidence at 3 years was 24.8 per 1000 person-years for SLE, 15.2 per 1000 person-years for CLE, 14.0 per 1000 person-years for psoriasis, and 10.3 per 1000 person-years for controls.
• Multivariable Cox proportional regression modeling showed ASCVD risk was highest in those with SLE (hazard ratio [HR], 2.23; P < .001) vs CLE (HR, 1.32; P < .001) and psoriasis (HR, 1.06; P = .09).
• ASCVD prevalence was higher in individuals with CLE receiving systemic therapy (2.7%) than in those receiving no therapy (1.6%), suggesting a potential link between disease severity and CVD risk.

IN PRACTICE:

“Persons with CLE are at higher risk for ASCVD, and guidelines for the evaluation and management of ASCVD may improve their quality of care,” the authors wrote.

SOURCE:

The study was led by Henry W. Chen, MD, Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. It was published online on December 4, 2024, in JAMA Dermatology.

LIMITATIONS: 

The study was limited by its relatively young population (median age, 49 years) and the exclusion of adults aged > 65 years on Medicare insurance plans. The database lacked race and ethnicity data, and the analysis was restricted to a shorter 3-year period. The study could not fully evaluate detailed risk factors such as blood pressure levels, cholesterol measurements, or glycemic control, nor could it accurately assess smoking status.

DISCLOSURES:

The research was supported by the Department of Dermatology at the University of Texas Southwestern Medical Center and a grant from the National Institutes of Health. Several authors reported receiving grants or personal fees from various pharmaceutical companies. One author reported being a deputy editor for diversity, equity, and inclusion at JAMA Cardiology. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Atherosclerotic cardiovascular disease (ASCVD) risk is higher with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) than with psoriasis.

METHODOLOGY:

• A retrospective matched longitudinal study compared the incidence and prevalence of ASCVD of 8138 individuals with CLE; 24,675 with SLE; 192,577 with psoriasis; and 81,380 control individuals.
• The disease-free control population was matched in a 10:1 ratio to the CLE population on the basis of age, sex, insurance type, and enrollment duration.
• Prevalent ASCVD was defined as coronary artery disease, prior myocardial infarction, or cerebrovascular accident, with ASCVD incidence assessed by number of hospitalizations over 3 years.

TAKEAWAY:

• Persons with CLE had higher ASCVD risk than control individuals (odds ratio [OR], 1.72; P < .001), similar to those with SLE (OR, 2.41; P < .001) but unlike those with psoriasis (OR, 1.03; P = .48).
• ASCVD incidence at 3 years was 24.8 per 1000 person-years for SLE, 15.2 per 1000 person-years for CLE, 14.0 per 1000 person-years for psoriasis, and 10.3 per 1000 person-years for controls.
• Multivariable Cox proportional regression modeling showed ASCVD risk was highest in those with SLE (hazard ratio [HR], 2.23; P < .001) vs CLE (HR, 1.32; P < .001) and psoriasis (HR, 1.06; P = .09).
• ASCVD prevalence was higher in individuals with CLE receiving systemic therapy (2.7%) than in those receiving no therapy (1.6%), suggesting a potential link between disease severity and CVD risk.

IN PRACTICE:

“Persons with CLE are at higher risk for ASCVD, and guidelines for the evaluation and management of ASCVD may improve their quality of care,” the authors wrote.

SOURCE:

The study was led by Henry W. Chen, MD, Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. It was published online on December 4, 2024, in JAMA Dermatology.

LIMITATIONS: 

The study was limited by its relatively young population (median age, 49 years) and the exclusion of adults aged > 65 years on Medicare insurance plans. The database lacked race and ethnicity data, and the analysis was restricted to a shorter 3-year period. The study could not fully evaluate detailed risk factors such as blood pressure levels, cholesterol measurements, or glycemic control, nor could it accurately assess smoking status.

DISCLOSURES:

The research was supported by the Department of Dermatology at the University of Texas Southwestern Medical Center and a grant from the National Institutes of Health. Several authors reported receiving grants or personal fees from various pharmaceutical companies. One author reported being a deputy editor for diversity, equity, and inclusion at JAMA Cardiology. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

New biologic drugs for chronic obstructive pulmonary disease (COPD) are finally here, said Stephen Rennard, MD, in a presentation in a session on new drugs at the 2024 GOLD International COPD Conference.

The inflammatory pathways associated with COPD are diverse and offer a range of potential targets for biologics, said Rennard, a professor of pulmonary, critical care, and sleep medicine at the University of Nebraska Medical Center, Omaha. 

The therapeutic goals of biologics remain the same as with other treatments for COPD, namely restoration of normal inflammatory response and alteration of disease progression, as well as restoration of lost structure and function and improvement of systemic effects, Rennard said in his presentation. Most studies of new and up-and-coming drugs have improvement in acute exacerbation of COPD as the primary outcome.

 

The Biology Behind the Biologics

T2 inflammation is “an inflammatory cascade led by IL [interleukin]-4, IL-13, and IL-5,” Mona Bafadhel, MD, chair of Respiratory Medicine at King’s College London in England, said in her presentation during the session.

Bafadhel, who served as one of the investigators on the BOREAS and NOTUS studies, explained some of the science behind the development of the new biologics.

Eosinophils are powerful regulators of immune response and inflammation by stimulating T-cell production and affecting other immune cell types, she noted.

In the context of COPD and drug development, high blood eosinophil counts have been associated with increased COPD-related exacerbations, Bafadhel said. She cited data from a Dutch study of more than 7000 patients with COPD (with and without clinical diagnoses), in which absolute eosinophil counts ≥ 3.3% were associated with increased risk for severe exacerbations of 32% and 84% across all patients with COPD and clinical COPD, respectively.

Understanding the mechanisms of the eosinophil in COPD is important for research and development, Bafadhel said. Along with standardizing measurement of T2 inflammatory markers (IL-4, IL-13, and IL-5), more research is needed to fully understand the role of eosinophils in immunoregulation and repair.

 

Fitting the Biologic to the Patient

Several recent studies of up-and-coming biologics have focused on subsets of COPD patients, said Dave Singh, MD, professor of clinical pharmacology and respiratory medicine at The University of Manchester in England, in his presentation at the meeting. In September 2024, the Food and Drug Administration approved dupilumab as the first biologic treatment for patients with uncontrolled COPD and type 2 inflammation on the basis of eosinophil counts. Singh cited data from the BOREAS and NOTUS studies in which dupilumab significantly reduced exacerbations and improved lung function in these patients, compared with a placebo.

Mepolizumab, a biologic approved for asthma, is not currently approved for COPD, but data from a 2017 study showed a trend toward reduced exacerbations, compared with placebo, in a subset of patients with high blood eosinophil counts, Singh said.

In addition, a recent unpublished phase 3 study (MATINEE) showed a reduction in the annualized rate of exacerbations, compared with placebo, on the basis of up to 2 years’ follow-up.

Singh also highlighted data from a phase 2a study of astegolimab, a biologic drug that focuses on the IL-33 receptor, in which COPD exacerbation rates were not significantly different between treatment and placebo groups. However, astegolimab has shown safety and efficacy in adults with severe asthma and is under development in phase 3 trials for COPD.

Tezepelumab, which was approved by the FDA in 2021 as an add-on therapy for severe asthma in patients aged 12 years or older, is also in development as a therapy for COPD exacerbations, Singh said.

In a study presented at the 2024 American Thoracic Society annual meeting, Singh and colleagues found that tezepelumab at a subcutaneous dose of 420 mg every 4 weeks reduced the annualized rate of moderate or severe COPD exacerbations compared with placebo based on data from approximately 300 patients, although the difference was not statistically significant.

Itepekimab, another biologic, showed promise in a phase 2a genetic association study involving current and former smokers with moderate to severe COPD, Singh said.

In that study, published in 2022 in The Lancet Respiratory Medicine, itepekimab failed to meet the primary endpoint in the overall study population of reduced annualized rate of moderate to severe exacerbations; however, a subgroup analysis of former smokers showed a significant (42%) reduction in exacerbations, Singh said in his presentation. Two phase 3 clinical studies (AERIFY-1/2) are ongoing to confirm the safety and efficacy of itepekimab in former smokers with COPD.

 

Takeaways and Next Steps

“These therapies provide the first new classes of medications approved for COPD in nearly 20 years,” said David M. Mannino, MD, of the University of Kentucky, Lexington, in an interview. “Dupilumab will be available to a subset of patients who are poorly controlled and have evidence of high eosinophils in their blood and is only used once every 2 weeks,” added Mannino, who has served as a consultant to companies developing COPD drugs.

Both dupilumab and ensifentrine, a phosphodiesterase (PDE) 3 and PDE4 inhibitor also recently approved for maintenance treatment of COPD, have been shown in clinical trials to reduce exacerbations and improve symptoms, said Mannino. Both offer additional options for patients who continue to have symptoms and exacerbations in spite of their current therapy.

Some barriers to the use of biologics in practice include the high cost. “Access and overcoming insurance-related issues such as preauthorization and high copays will be a challenge,” he said. Also, because dupilumab is an injectable drug, some patient training will be required.

Newer biologic therapies in development are also injectables, but some studies are examining longer time intervals as long as every 6 months, which could be a major advancement for some patients. The newer therapies in development are similar to dupilumab in that they will be injected therapies. Some in development are looking at longer time intervals as long as every 6 months, which may be a major advancement for some patients. “All of these therapies, however, are currently targeting more advanced or serious disease,” he said.

Looking ahead, more therapies are needed for the treatment of early COPD, as well as therapies that can be administered to a large number of patients at a reasonable cost, Mannino added.

Rennard disclosed serving as a consultant for Verona Pharma, Sanofi, Beyond Air, RS BioTherapeutics, RespirAI, and Roche, as well as speaker fees from Sanofi and temporary ownership interest while employed by AstraZeneca. Rennard is also the founder of Great Plains Biometrix. Bafadhel disclosed funding from the National Institute for Health Research (NIHR), grants from Asthma + Lung UK, Horizon Europe, NIHR, and AstraZeneca to her institution, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer. Singh disclosed relationships including speaking sponsorships, honoraria, and advisory board memberships for Adovate, Aerogen, Almirall, Apogee, Arrowhead, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, Connect Biopharm, Covis, CSL Behring, DevPro Biopharm, Elpen, Empirico, EpiEndo, Genentech, Generate Biomedicines, GlaxoSmithKline, Glenmark, Kamada, Kinaset Therapeutics, Kymera, Menarini, MicroA, OM Pharma, Orion, Pieris Pharmaceuticals, Pulmatrix, Revolo, Roivant Sciences, Sanofi, Synairgen, Tetherex, Teva, Theravance Biopharma, Upstream, and Verona Pharma. Mannino disclosed serving as a consultant to multiple companies currently developing COPD therapies (AstraZeneca, GlaxoSmithKline, Roche, Regeneron, Sanofi, Genentech, Amgen, and Chiesi).

A version of this article appeared on Medscape.com.

New biologic drugs for chronic obstructive pulmonary disease (COPD) are finally here, said Stephen Rennard, MD, in a presentation in a session on new drugs at the 2024 GOLD International COPD Conference.

The inflammatory pathways associated with COPD are diverse and offer a range of potential targets for biologics, said Rennard, a professor of pulmonary, critical care, and sleep medicine at the University of Nebraska Medical Center, Omaha. 

The therapeutic goals of biologics remain the same as with other treatments for COPD, namely restoration of normal inflammatory response and alteration of disease progression, as well as restoration of lost structure and function and improvement of systemic effects, Rennard said in his presentation. Most studies of new and up-and-coming drugs have improvement in acute exacerbation of COPD as the primary outcome.

 

The Biology Behind the Biologics

T2 inflammation is “an inflammatory cascade led by IL [interleukin]-4, IL-13, and IL-5,” Mona Bafadhel, MD, chair of Respiratory Medicine at King’s College London in England, said in her presentation during the session.

Bafadhel, who served as one of the investigators on the BOREAS and NOTUS studies, explained some of the science behind the development of the new biologics.

Eosinophils are powerful regulators of immune response and inflammation by stimulating T-cell production and affecting other immune cell types, she noted.

In the context of COPD and drug development, high blood eosinophil counts have been associated with increased COPD-related exacerbations, Bafadhel said. She cited data from a Dutch study of more than 7000 patients with COPD (with and without clinical diagnoses), in which absolute eosinophil counts ≥ 3.3% were associated with increased risk for severe exacerbations of 32% and 84% across all patients with COPD and clinical COPD, respectively.

Understanding the mechanisms of the eosinophil in COPD is important for research and development, Bafadhel said. Along with standardizing measurement of T2 inflammatory markers (IL-4, IL-13, and IL-5), more research is needed to fully understand the role of eosinophils in immunoregulation and repair.

 

Fitting the Biologic to the Patient

Several recent studies of up-and-coming biologics have focused on subsets of COPD patients, said Dave Singh, MD, professor of clinical pharmacology and respiratory medicine at The University of Manchester in England, in his presentation at the meeting. In September 2024, the Food and Drug Administration approved dupilumab as the first biologic treatment for patients with uncontrolled COPD and type 2 inflammation on the basis of eosinophil counts. Singh cited data from the BOREAS and NOTUS studies in which dupilumab significantly reduced exacerbations and improved lung function in these patients, compared with a placebo.

Mepolizumab, a biologic approved for asthma, is not currently approved for COPD, but data from a 2017 study showed a trend toward reduced exacerbations, compared with placebo, in a subset of patients with high blood eosinophil counts, Singh said.

In addition, a recent unpublished phase 3 study (MATINEE) showed a reduction in the annualized rate of exacerbations, compared with placebo, on the basis of up to 2 years’ follow-up.

Singh also highlighted data from a phase 2a study of astegolimab, a biologic drug that focuses on the IL-33 receptor, in which COPD exacerbation rates were not significantly different between treatment and placebo groups. However, astegolimab has shown safety and efficacy in adults with severe asthma and is under development in phase 3 trials for COPD.

Tezepelumab, which was approved by the FDA in 2021 as an add-on therapy for severe asthma in patients aged 12 years or older, is also in development as a therapy for COPD exacerbations, Singh said.

In a study presented at the 2024 American Thoracic Society annual meeting, Singh and colleagues found that tezepelumab at a subcutaneous dose of 420 mg every 4 weeks reduced the annualized rate of moderate or severe COPD exacerbations compared with placebo based on data from approximately 300 patients, although the difference was not statistically significant.

Itepekimab, another biologic, showed promise in a phase 2a genetic association study involving current and former smokers with moderate to severe COPD, Singh said.

In that study, published in 2022 in The Lancet Respiratory Medicine, itepekimab failed to meet the primary endpoint in the overall study population of reduced annualized rate of moderate to severe exacerbations; however, a subgroup analysis of former smokers showed a significant (42%) reduction in exacerbations, Singh said in his presentation. Two phase 3 clinical studies (AERIFY-1/2) are ongoing to confirm the safety and efficacy of itepekimab in former smokers with COPD.

 

Takeaways and Next Steps

“These therapies provide the first new classes of medications approved for COPD in nearly 20 years,” said David M. Mannino, MD, of the University of Kentucky, Lexington, in an interview. “Dupilumab will be available to a subset of patients who are poorly controlled and have evidence of high eosinophils in their blood and is only used once every 2 weeks,” added Mannino, who has served as a consultant to companies developing COPD drugs.

Both dupilumab and ensifentrine, a phosphodiesterase (PDE) 3 and PDE4 inhibitor also recently approved for maintenance treatment of COPD, have been shown in clinical trials to reduce exacerbations and improve symptoms, said Mannino. Both offer additional options for patients who continue to have symptoms and exacerbations in spite of their current therapy.

Some barriers to the use of biologics in practice include the high cost. “Access and overcoming insurance-related issues such as preauthorization and high copays will be a challenge,” he said. Also, because dupilumab is an injectable drug, some patient training will be required.

Newer biologic therapies in development are also injectables, but some studies are examining longer time intervals as long as every 6 months, which could be a major advancement for some patients. The newer therapies in development are similar to dupilumab in that they will be injected therapies. Some in development are looking at longer time intervals as long as every 6 months, which may be a major advancement for some patients. “All of these therapies, however, are currently targeting more advanced or serious disease,” he said.

Looking ahead, more therapies are needed for the treatment of early COPD, as well as therapies that can be administered to a large number of patients at a reasonable cost, Mannino added.

Rennard disclosed serving as a consultant for Verona Pharma, Sanofi, Beyond Air, RS BioTherapeutics, RespirAI, and Roche, as well as speaker fees from Sanofi and temporary ownership interest while employed by AstraZeneca. Rennard is also the founder of Great Plains Biometrix. Bafadhel disclosed funding from the National Institute for Health Research (NIHR), grants from Asthma + Lung UK, Horizon Europe, NIHR, and AstraZeneca to her institution, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer. Singh disclosed relationships including speaking sponsorships, honoraria, and advisory board memberships for Adovate, Aerogen, Almirall, Apogee, Arrowhead, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, Connect Biopharm, Covis, CSL Behring, DevPro Biopharm, Elpen, Empirico, EpiEndo, Genentech, Generate Biomedicines, GlaxoSmithKline, Glenmark, Kamada, Kinaset Therapeutics, Kymera, Menarini, MicroA, OM Pharma, Orion, Pieris Pharmaceuticals, Pulmatrix, Revolo, Roivant Sciences, Sanofi, Synairgen, Tetherex, Teva, Theravance Biopharma, Upstream, and Verona Pharma. Mannino disclosed serving as a consultant to multiple companies currently developing COPD therapies (AstraZeneca, GlaxoSmithKline, Roche, Regeneron, Sanofi, Genentech, Amgen, and Chiesi).

A version of this article appeared on Medscape.com.

New biologic drugs for chronic obstructive pulmonary disease (COPD) are finally here, said Stephen Rennard, MD, in a presentation in a session on new drugs at the 2024 GOLD International COPD Conference.

The inflammatory pathways associated with COPD are diverse and offer a range of potential targets for biologics, said Rennard, a professor of pulmonary, critical care, and sleep medicine at the University of Nebraska Medical Center, Omaha. 

The therapeutic goals of biologics remain the same as with other treatments for COPD, namely restoration of normal inflammatory response and alteration of disease progression, as well as restoration of lost structure and function and improvement of systemic effects, Rennard said in his presentation. Most studies of new and up-and-coming drugs have improvement in acute exacerbation of COPD as the primary outcome.

 

The Biology Behind the Biologics

T2 inflammation is “an inflammatory cascade led by IL [interleukin]-4, IL-13, and IL-5,” Mona Bafadhel, MD, chair of Respiratory Medicine at King’s College London in England, said in her presentation during the session.

Bafadhel, who served as one of the investigators on the BOREAS and NOTUS studies, explained some of the science behind the development of the new biologics.

Eosinophils are powerful regulators of immune response and inflammation by stimulating T-cell production and affecting other immune cell types, she noted.

In the context of COPD and drug development, high blood eosinophil counts have been associated with increased COPD-related exacerbations, Bafadhel said. She cited data from a Dutch study of more than 7000 patients with COPD (with and without clinical diagnoses), in which absolute eosinophil counts ≥ 3.3% were associated with increased risk for severe exacerbations of 32% and 84% across all patients with COPD and clinical COPD, respectively.

Understanding the mechanisms of the eosinophil in COPD is important for research and development, Bafadhel said. Along with standardizing measurement of T2 inflammatory markers (IL-4, IL-13, and IL-5), more research is needed to fully understand the role of eosinophils in immunoregulation and repair.

 

Fitting the Biologic to the Patient

Several recent studies of up-and-coming biologics have focused on subsets of COPD patients, said Dave Singh, MD, professor of clinical pharmacology and respiratory medicine at The University of Manchester in England, in his presentation at the meeting. In September 2024, the Food and Drug Administration approved dupilumab as the first biologic treatment for patients with uncontrolled COPD and type 2 inflammation on the basis of eosinophil counts. Singh cited data from the BOREAS and NOTUS studies in which dupilumab significantly reduced exacerbations and improved lung function in these patients, compared with a placebo.

Mepolizumab, a biologic approved for asthma, is not currently approved for COPD, but data from a 2017 study showed a trend toward reduced exacerbations, compared with placebo, in a subset of patients with high blood eosinophil counts, Singh said.

In addition, a recent unpublished phase 3 study (MATINEE) showed a reduction in the annualized rate of exacerbations, compared with placebo, on the basis of up to 2 years’ follow-up.

Singh also highlighted data from a phase 2a study of astegolimab, a biologic drug that focuses on the IL-33 receptor, in which COPD exacerbation rates were not significantly different between treatment and placebo groups. However, astegolimab has shown safety and efficacy in adults with severe asthma and is under development in phase 3 trials for COPD.

Tezepelumab, which was approved by the FDA in 2021 as an add-on therapy for severe asthma in patients aged 12 years or older, is also in development as a therapy for COPD exacerbations, Singh said.

In a study presented at the 2024 American Thoracic Society annual meeting, Singh and colleagues found that tezepelumab at a subcutaneous dose of 420 mg every 4 weeks reduced the annualized rate of moderate or severe COPD exacerbations compared with placebo based on data from approximately 300 patients, although the difference was not statistically significant.

Itepekimab, another biologic, showed promise in a phase 2a genetic association study involving current and former smokers with moderate to severe COPD, Singh said.

In that study, published in 2022 in The Lancet Respiratory Medicine, itepekimab failed to meet the primary endpoint in the overall study population of reduced annualized rate of moderate to severe exacerbations; however, a subgroup analysis of former smokers showed a significant (42%) reduction in exacerbations, Singh said in his presentation. Two phase 3 clinical studies (AERIFY-1/2) are ongoing to confirm the safety and efficacy of itepekimab in former smokers with COPD.

 

Takeaways and Next Steps

“These therapies provide the first new classes of medications approved for COPD in nearly 20 years,” said David M. Mannino, MD, of the University of Kentucky, Lexington, in an interview. “Dupilumab will be available to a subset of patients who are poorly controlled and have evidence of high eosinophils in their blood and is only used once every 2 weeks,” added Mannino, who has served as a consultant to companies developing COPD drugs.

Both dupilumab and ensifentrine, a phosphodiesterase (PDE) 3 and PDE4 inhibitor also recently approved for maintenance treatment of COPD, have been shown in clinical trials to reduce exacerbations and improve symptoms, said Mannino. Both offer additional options for patients who continue to have symptoms and exacerbations in spite of their current therapy.

Some barriers to the use of biologics in practice include the high cost. “Access and overcoming insurance-related issues such as preauthorization and high copays will be a challenge,” he said. Also, because dupilumab is an injectable drug, some patient training will be required.

Newer biologic therapies in development are also injectables, but some studies are examining longer time intervals as long as every 6 months, which could be a major advancement for some patients. The newer therapies in development are similar to dupilumab in that they will be injected therapies. Some in development are looking at longer time intervals as long as every 6 months, which may be a major advancement for some patients. “All of these therapies, however, are currently targeting more advanced or serious disease,” he said.

Looking ahead, more therapies are needed for the treatment of early COPD, as well as therapies that can be administered to a large number of patients at a reasonable cost, Mannino added.

Rennard disclosed serving as a consultant for Verona Pharma, Sanofi, Beyond Air, RS BioTherapeutics, RespirAI, and Roche, as well as speaker fees from Sanofi and temporary ownership interest while employed by AstraZeneca. Rennard is also the founder of Great Plains Biometrix. Bafadhel disclosed funding from the National Institute for Health Research (NIHR), grants from Asthma + Lung UK, Horizon Europe, NIHR, and AstraZeneca to her institution, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer. Singh disclosed relationships including speaking sponsorships, honoraria, and advisory board memberships for Adovate, Aerogen, Almirall, Apogee, Arrowhead, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, Connect Biopharm, Covis, CSL Behring, DevPro Biopharm, Elpen, Empirico, EpiEndo, Genentech, Generate Biomedicines, GlaxoSmithKline, Glenmark, Kamada, Kinaset Therapeutics, Kymera, Menarini, MicroA, OM Pharma, Orion, Pieris Pharmaceuticals, Pulmatrix, Revolo, Roivant Sciences, Sanofi, Synairgen, Tetherex, Teva, Theravance Biopharma, Upstream, and Verona Pharma. Mannino disclosed serving as a consultant to multiple companies currently developing COPD therapies (AstraZeneca, GlaxoSmithKline, Roche, Regeneron, Sanofi, Genentech, Amgen, and Chiesi).

A version of this article appeared on Medscape.com.

Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

 

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

 

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet. 

 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:

• Overnight international hospitalization
• Recent stay in a long-term acute care facility
• Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.

 

A version of this article appeared on Medscape.com.

Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

 

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

 

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet. 

 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:

• Overnight international hospitalization
• Recent stay in a long-term acute care facility
• Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.

 

A version of this article appeared on Medscape.com.

Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

 

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

 

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet. 

 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:

• Overnight international hospitalization
• Recent stay in a long-term acute care facility
• Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.

 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.

This is an issue that we must address, I think, epidemiologically. We know that early-onset colorectal cancer is defined as a disease arising in those under the age of 50. There’s been a very sharp increase globally over the past 20-30 years, and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.

The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease. 

There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.

The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.

Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.

They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age. 

All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later. 

This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it. 

Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.

More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology. 

I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.

This is an issue that we must address, I think, epidemiologically. We know that early-onset colorectal cancer is defined as a disease arising in those under the age of 50. There’s been a very sharp increase globally over the past 20-30 years, and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.

The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease. 

There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.

The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.

Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.

They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age. 

All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later. 

This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it. 

Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.

More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology. 

I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.

This is an issue that we must address, I think, epidemiologically. We know that early-onset colorectal cancer is defined as a disease arising in those under the age of 50. There’s been a very sharp increase globally over the past 20-30 years, and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.

The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease. 

There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.

The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.

Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.

They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age. 

All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later. 

This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it. 

Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.

More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology. 

I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche. 

A version of this article appeared on Medscape.com.

It’s been a while since I’ve discussed the H5N1 avian influenza clade 2.3.4.4b and its rapid spread in North America. I hope the facts prove me wrong, but many experts have been warning for some time that ideal conditions are forming for this virus, which for now only causes zoonoses, to pose a pandemic threat.

Let me recap for anyone who may have missed some of the developments, either because they work in other medical fields or think that the experience of the COVID-19 pandemic was a worst-case scenario that is unlikely to be repeated in the short term.

 

The Virus Has Flown to Hawaii

According to data from the Centers for Disease Control and Prevention in Atlanta, Georgia, the infection has now affected more than 500 cattle herds in 15 states. There are about 30 outbreaks reported in poultry, equally distributed between backyard and farm-raised birds, primarily located in California. Here alone, over 3 million birds have been affected. 

Wild birds are believed to have transported the highly pathogenic virus via migration routes across the Pacific, introducing it to Hawaii for the first time. Just days after wastewater analysis detected the presence of H5N1 on the island of Oahu, home to the capital Honolulu, the first outbreak was promptly reported, killing at least a dozen ducks and geese in a backyard coop. Some of these birds had been taken in early November to the Mililani Pet Fair, a sort of domestic animal festival. Local authorities recommended that anyone who attended the fair, touched a duck or goose at the event, and developed symptoms including fever, cough, sore throat, and conjunctivitis, should isolate and seek medical advice.

Meanwhile, more than 50 farmers, animal handlers, or workers involved in the slaughter of cattle or poultry across seven states have been confirmed infected, presumably contracted at their workplace. The latest case, diagnosed recently in Oregon, presented with severe conjunctivitis and mild respiratory symptoms. More than half of these patients have been identified in recent weeks in California, where active surveillance measures have been implemented. However, there is strong suspicion that the actual number of people infected with mild symptoms in the rest of the country is much, much higher.

 

The Red Alert Lights Up in Canada

The level of concern was raised further with news of the first severe — indeed very severe — case of H5N1 avian influenza originating from the western edge of Canada. A teenager (gender not disclosed), previously healthy and without risk factors, was hospitalized with severe respiratory failure in the intensive care unit at British Columbia Children’s Hospital in Vancouver. The source of the infection is unknown, similar to only one other case in Missouri involving an adult already hospitalized for other reasons, which was identified by chance through influenza surveillance programs. We also know that the Canadian adolescent does not live on a farm and had no known contact with potentially infected animals. The only suspicions focus on the family dog, euthanized owing to unspecified health problems in the early days of the epidemiologic investigation. Although the dog tested negative for avian influenza, a necropsy will be conducted to rule out its involvement in the transmission chain.

An initial characterization of the virus has linked it to genotype D1.1, which is circulating among wild birds and poultry farms in Canada’s westernmost province, rather than the strain typical of dairy cows in the United States. The publication of the complete viral sequence over the past weekend has, for the first time, highlighted mutations that could enhance the virus’s ability to infect human cells.

How do we know this? From the highly contested “gain-of-function” studies, which artificially modify viruses to understand which genomic points require the most surveillance — those mutations that can make the infectious agent more virulent or more transmissible between people.

 

Under Special Surveillance for 20 Years

The influenza A (H5N1) avian virus is not new or previously unknown, like SARS-CoV-2, and this could (in theory) give us a slight advantage. We have known about it for decades, and it began infecting humans about 20 years ago, causing pneumonia with respiratory failure. It proved lethal in about half of the cases, but only in people who had close contact with infected poultry, primarily in Southeast Asia.

Hundreds of other human cases occurred worldwide, but always in low-income countries with poor hygiene conditions and where families lived in close contact with animals. This contributed to a false sense of security in Europe and North America, where the threat has been consistently underestimated. Despite an estimated fatality rate of around 50%, the media often labeled scientists’ warnings and health authorities’ efforts to remain prepared as false alarms, tainted by suspicions of catering to the interests of pharmaceutical companies.

Some people may recall the scandal involving Tamiflu, the Roche antiviral oseltamivir, that governments stockpiled when there were fears that the avian virus might acquire the ability to spread among humans. It was dubbed “a false antidote for a false pandemic,” referring to the potential avian pandemic and the 2009 H1N1 influenza pandemic, improperly called “swine flu,” and which turned out to be less severe than expected. There was talk of €2.64 billion being “wasted” to “please” the manufacturer. Although the Cochrane Collaboration made legitimate demands for rigor and transparency in conducting and publishing clinical trials, much of the public, and the journalists who wrote the stories, cared little about these technical aspects. The prevailing message was that stockpiling drugs (or vaccines) for a disease we don’t even know will occur is a waste of taxpayers’ money rather than a prudent preventive measure.

 

More Vulnerable Than Ever

If we were to ascribe strategic thinking to the virus, which it is not capable of, we might argue that it chose the ideal moment to conquer the world. It began circulating in the new clade in 2020, when experts and authorities were focused on the coronavirus. It spread from birds to marine mammals and finally to cattle, exploiting the public’s post-pandemic fatigue, as people no longer wanted to hear about infectious diseases and containment measures. It ultimately rode the wave of political polarization that irrationally equates prevention with supposed cowardice on the left, and recklessness with courageous freedom on the right.

The coincidence between the future appointments announced by the incoming Trump administration and the virus’s accelerated spread deserves attention from decision-makers and health professionals worldwide. The COVID-19 pandemic experience should have taught us that ignoring a threat doesn’t make it go away, if not in our health, then at least in our wallet. The economic repercussions of a virus circulating among animals crucial to our food chain and national economies should concern everyone, well before the threat crosses the ocean, because only then can we defend ourselves.

The proposed Secretary of Health and Human Services, Robert F. Kennedy, is a proponent of the supposed benefits of raw milk, which could serve as a potent vector for the virus. He is ideologically opposed to vaccinations. It’s hard to imagine he would utilize the H5N1 vaccine stockpiles held by the US government for a campaign starting at least with farmers, as was done prophylactically in Finland with products jointly procured by 15 European countries — a group the Italian government decided not to join.

If Kennedy indeed becomes responsible for US public health, it’s reasonable to fear that, in the name of freedom, he will try to delay as much as possible — even if necessary — the obligation to undergo testing and wear masks, not to mention more restrictive infection containment measures. It’s also unlikely he would support and promote the development of new mRNA products already under study, which would become indispensable if the disease begins to spread more easily among people, as well as animals. In such a case, traditional influenza vaccine cultivation methods using chicken eggs would prove too slow and quantitatively insufficient, especially if the virus continues to circulate among poultry.

In short, let’s keep our fingers crossed, but recognize that crossing our fingers might not be enough.

This story was translated from Univadis Italy using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

It’s been a while since I’ve discussed the H5N1 avian influenza clade 2.3.4.4b and its rapid spread in North America. I hope the facts prove me wrong, but many experts have been warning for some time that ideal conditions are forming for this virus, which for now only causes zoonoses, to pose a pandemic threat.

Let me recap for anyone who may have missed some of the developments, either because they work in other medical fields or think that the experience of the COVID-19 pandemic was a worst-case scenario that is unlikely to be repeated in the short term.

 

The Virus Has Flown to Hawaii

According to data from the Centers for Disease Control and Prevention in Atlanta, Georgia, the infection has now affected more than 500 cattle herds in 15 states. There are about 30 outbreaks reported in poultry, equally distributed between backyard and farm-raised birds, primarily located in California. Here alone, over 3 million birds have been affected. 

Wild birds are believed to have transported the highly pathogenic virus via migration routes across the Pacific, introducing it to Hawaii for the first time. Just days after wastewater analysis detected the presence of H5N1 on the island of Oahu, home to the capital Honolulu, the first outbreak was promptly reported, killing at least a dozen ducks and geese in a backyard coop. Some of these birds had been taken in early November to the Mililani Pet Fair, a sort of domestic animal festival. Local authorities recommended that anyone who attended the fair, touched a duck or goose at the event, and developed symptoms including fever, cough, sore throat, and conjunctivitis, should isolate and seek medical advice.

Meanwhile, more than 50 farmers, animal handlers, or workers involved in the slaughter of cattle or poultry across seven states have been confirmed infected, presumably contracted at their workplace. The latest case, diagnosed recently in Oregon, presented with severe conjunctivitis and mild respiratory symptoms. More than half of these patients have been identified in recent weeks in California, where active surveillance measures have been implemented. However, there is strong suspicion that the actual number of people infected with mild symptoms in the rest of the country is much, much higher.

 

The Red Alert Lights Up in Canada

The level of concern was raised further with news of the first severe — indeed very severe — case of H5N1 avian influenza originating from the western edge of Canada. A teenager (gender not disclosed), previously healthy and without risk factors, was hospitalized with severe respiratory failure in the intensive care unit at British Columbia Children’s Hospital in Vancouver. The source of the infection is unknown, similar to only one other case in Missouri involving an adult already hospitalized for other reasons, which was identified by chance through influenza surveillance programs. We also know that the Canadian adolescent does not live on a farm and had no known contact with potentially infected animals. The only suspicions focus on the family dog, euthanized owing to unspecified health problems in the early days of the epidemiologic investigation. Although the dog tested negative for avian influenza, a necropsy will be conducted to rule out its involvement in the transmission chain.

An initial characterization of the virus has linked it to genotype D1.1, which is circulating among wild birds and poultry farms in Canada’s westernmost province, rather than the strain typical of dairy cows in the United States. The publication of the complete viral sequence over the past weekend has, for the first time, highlighted mutations that could enhance the virus’s ability to infect human cells.

How do we know this? From the highly contested “gain-of-function” studies, which artificially modify viruses to understand which genomic points require the most surveillance — those mutations that can make the infectious agent more virulent or more transmissible between people.

 

Under Special Surveillance for 20 Years

The influenza A (H5N1) avian virus is not new or previously unknown, like SARS-CoV-2, and this could (in theory) give us a slight advantage. We have known about it for decades, and it began infecting humans about 20 years ago, causing pneumonia with respiratory failure. It proved lethal in about half of the cases, but only in people who had close contact with infected poultry, primarily in Southeast Asia.

Hundreds of other human cases occurred worldwide, but always in low-income countries with poor hygiene conditions and where families lived in close contact with animals. This contributed to a false sense of security in Europe and North America, where the threat has been consistently underestimated. Despite an estimated fatality rate of around 50%, the media often labeled scientists’ warnings and health authorities’ efforts to remain prepared as false alarms, tainted by suspicions of catering to the interests of pharmaceutical companies.

Some people may recall the scandal involving Tamiflu, the Roche antiviral oseltamivir, that governments stockpiled when there were fears that the avian virus might acquire the ability to spread among humans. It was dubbed “a false antidote for a false pandemic,” referring to the potential avian pandemic and the 2009 H1N1 influenza pandemic, improperly called “swine flu,” and which turned out to be less severe than expected. There was talk of €2.64 billion being “wasted” to “please” the manufacturer. Although the Cochrane Collaboration made legitimate demands for rigor and transparency in conducting and publishing clinical trials, much of the public, and the journalists who wrote the stories, cared little about these technical aspects. The prevailing message was that stockpiling drugs (or vaccines) for a disease we don’t even know will occur is a waste of taxpayers’ money rather than a prudent preventive measure.

 

More Vulnerable Than Ever

If we were to ascribe strategic thinking to the virus, which it is not capable of, we might argue that it chose the ideal moment to conquer the world. It began circulating in the new clade in 2020, when experts and authorities were focused on the coronavirus. It spread from birds to marine mammals and finally to cattle, exploiting the public’s post-pandemic fatigue, as people no longer wanted to hear about infectious diseases and containment measures. It ultimately rode the wave of political polarization that irrationally equates prevention with supposed cowardice on the left, and recklessness with courageous freedom on the right.

The coincidence between the future appointments announced by the incoming Trump administration and the virus’s accelerated spread deserves attention from decision-makers and health professionals worldwide. The COVID-19 pandemic experience should have taught us that ignoring a threat doesn’t make it go away, if not in our health, then at least in our wallet. The economic repercussions of a virus circulating among animals crucial to our food chain and national economies should concern everyone, well before the threat crosses the ocean, because only then can we defend ourselves.

The proposed Secretary of Health and Human Services, Robert F. Kennedy, is a proponent of the supposed benefits of raw milk, which could serve as a potent vector for the virus. He is ideologically opposed to vaccinations. It’s hard to imagine he would utilize the H5N1 vaccine stockpiles held by the US government for a campaign starting at least with farmers, as was done prophylactically in Finland with products jointly procured by 15 European countries — a group the Italian government decided not to join.

If Kennedy indeed becomes responsible for US public health, it’s reasonable to fear that, in the name of freedom, he will try to delay as much as possible — even if necessary — the obligation to undergo testing and wear masks, not to mention more restrictive infection containment measures. It’s also unlikely he would support and promote the development of new mRNA products already under study, which would become indispensable if the disease begins to spread more easily among people, as well as animals. In such a case, traditional influenza vaccine cultivation methods using chicken eggs would prove too slow and quantitatively insufficient, especially if the virus continues to circulate among poultry.

In short, let’s keep our fingers crossed, but recognize that crossing our fingers might not be enough.

This story was translated from Univadis Italy using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

It’s been a while since I’ve discussed the H5N1 avian influenza clade 2.3.4.4b and its rapid spread in North America. I hope the facts prove me wrong, but many experts have been warning for some time that ideal conditions are forming for this virus, which for now only causes zoonoses, to pose a pandemic threat.

Let me recap for anyone who may have missed some of the developments, either because they work in other medical fields or think that the experience of the COVID-19 pandemic was a worst-case scenario that is unlikely to be repeated in the short term.

 

The Virus Has Flown to Hawaii

According to data from the Centers for Disease Control and Prevention in Atlanta, Georgia, the infection has now affected more than 500 cattle herds in 15 states. There are about 30 outbreaks reported in poultry, equally distributed between backyard and farm-raised birds, primarily located in California. Here alone, over 3 million birds have been affected. 

Wild birds are believed to have transported the highly pathogenic virus via migration routes across the Pacific, introducing it to Hawaii for the first time. Just days after wastewater analysis detected the presence of H5N1 on the island of Oahu, home to the capital Honolulu, the first outbreak was promptly reported, killing at least a dozen ducks and geese in a backyard coop. Some of these birds had been taken in early November to the Mililani Pet Fair, a sort of domestic animal festival. Local authorities recommended that anyone who attended the fair, touched a duck or goose at the event, and developed symptoms including fever, cough, sore throat, and conjunctivitis, should isolate and seek medical advice.

Meanwhile, more than 50 farmers, animal handlers, or workers involved in the slaughter of cattle or poultry across seven states have been confirmed infected, presumably contracted at their workplace. The latest case, diagnosed recently in Oregon, presented with severe conjunctivitis and mild respiratory symptoms. More than half of these patients have been identified in recent weeks in California, where active surveillance measures have been implemented. However, there is strong suspicion that the actual number of people infected with mild symptoms in the rest of the country is much, much higher.

 

The Red Alert Lights Up in Canada

The level of concern was raised further with news of the first severe — indeed very severe — case of H5N1 avian influenza originating from the western edge of Canada. A teenager (gender not disclosed), previously healthy and without risk factors, was hospitalized with severe respiratory failure in the intensive care unit at British Columbia Children’s Hospital in Vancouver. The source of the infection is unknown, similar to only one other case in Missouri involving an adult already hospitalized for other reasons, which was identified by chance through influenza surveillance programs. We also know that the Canadian adolescent does not live on a farm and had no known contact with potentially infected animals. The only suspicions focus on the family dog, euthanized owing to unspecified health problems in the early days of the epidemiologic investigation. Although the dog tested negative for avian influenza, a necropsy will be conducted to rule out its involvement in the transmission chain.

An initial characterization of the virus has linked it to genotype D1.1, which is circulating among wild birds and poultry farms in Canada’s westernmost province, rather than the strain typical of dairy cows in the United States. The publication of the complete viral sequence over the past weekend has, for the first time, highlighted mutations that could enhance the virus’s ability to infect human cells.

How do we know this? From the highly contested “gain-of-function” studies, which artificially modify viruses to understand which genomic points require the most surveillance — those mutations that can make the infectious agent more virulent or more transmissible between people.

 

Under Special Surveillance for 20 Years

The influenza A (H5N1) avian virus is not new or previously unknown, like SARS-CoV-2, and this could (in theory) give us a slight advantage. We have known about it for decades, and it began infecting humans about 20 years ago, causing pneumonia with respiratory failure. It proved lethal in about half of the cases, but only in people who had close contact with infected poultry, primarily in Southeast Asia.

Hundreds of other human cases occurred worldwide, but always in low-income countries with poor hygiene conditions and where families lived in close contact with animals. This contributed to a false sense of security in Europe and North America, where the threat has been consistently underestimated. Despite an estimated fatality rate of around 50%, the media often labeled scientists’ warnings and health authorities’ efforts to remain prepared as false alarms, tainted by suspicions of catering to the interests of pharmaceutical companies.

Some people may recall the scandal involving Tamiflu, the Roche antiviral oseltamivir, that governments stockpiled when there were fears that the avian virus might acquire the ability to spread among humans. It was dubbed “a false antidote for a false pandemic,” referring to the potential avian pandemic and the 2009 H1N1 influenza pandemic, improperly called “swine flu,” and which turned out to be less severe than expected. There was talk of €2.64 billion being “wasted” to “please” the manufacturer. Although the Cochrane Collaboration made legitimate demands for rigor and transparency in conducting and publishing clinical trials, much of the public, and the journalists who wrote the stories, cared little about these technical aspects. The prevailing message was that stockpiling drugs (or vaccines) for a disease we don’t even know will occur is a waste of taxpayers’ money rather than a prudent preventive measure.

 

More Vulnerable Than Ever

If we were to ascribe strategic thinking to the virus, which it is not capable of, we might argue that it chose the ideal moment to conquer the world. It began circulating in the new clade in 2020, when experts and authorities were focused on the coronavirus. It spread from birds to marine mammals and finally to cattle, exploiting the public’s post-pandemic fatigue, as people no longer wanted to hear about infectious diseases and containment measures. It ultimately rode the wave of political polarization that irrationally equates prevention with supposed cowardice on the left, and recklessness with courageous freedom on the right.

The coincidence between the future appointments announced by the incoming Trump administration and the virus’s accelerated spread deserves attention from decision-makers and health professionals worldwide. The COVID-19 pandemic experience should have taught us that ignoring a threat doesn’t make it go away, if not in our health, then at least in our wallet. The economic repercussions of a virus circulating among animals crucial to our food chain and national economies should concern everyone, well before the threat crosses the ocean, because only then can we defend ourselves.

The proposed Secretary of Health and Human Services, Robert F. Kennedy, is a proponent of the supposed benefits of raw milk, which could serve as a potent vector for the virus. He is ideologically opposed to vaccinations. It’s hard to imagine he would utilize the H5N1 vaccine stockpiles held by the US government for a campaign starting at least with farmers, as was done prophylactically in Finland with products jointly procured by 15 European countries — a group the Italian government decided not to join.

If Kennedy indeed becomes responsible for US public health, it’s reasonable to fear that, in the name of freedom, he will try to delay as much as possible — even if necessary — the obligation to undergo testing and wear masks, not to mention more restrictive infection containment measures. It’s also unlikely he would support and promote the development of new mRNA products already under study, which would become indispensable if the disease begins to spread more easily among people, as well as animals. In such a case, traditional influenza vaccine cultivation methods using chicken eggs would prove too slow and quantitatively insufficient, especially if the virus continues to circulate among poultry.

In short, let’s keep our fingers crossed, but recognize that crossing our fingers might not be enough.

This story was translated from Univadis Italy using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Children with atopic dermatitis, even of greater severity, do not experience a delay in attaining pubertal milestones.

METHODOLOGY:

• Investigators conducted a nationwide cohort study among 15,534 children in Denmark whose pubertal development was assessed every 6 months with a web-based questionnaire starting at the age of 11 years.
• The children were classified into three groups: No atopic dermatitis; self-reported doctor-diagnosed atopic dermatitis (maternal report of a doctor diagnosis at 6 months, 18 months, and/or 7 years of age); hospital-diagnosed atopic dermatitis (registry data showing it as the primary reason for hospital contact up to the age of 8 years), representing mainly severe cases.
• The main outcome was the age difference averaged across a range of pubertal milestones (attainment of Tanner stages; development of axillary hair, acne, and voice break; and occurrence of first ejaculation and menarche).

TAKEAWAY:

• Overall, 21.5% of the children had self-reported doctor-diagnosed atopic dermatitis and 0.7% had hospital-diagnosed atopic dermatitis.
• Relative to girls without atopic dermatitis, girls with self-reported doctor-diagnosed atopic dermatitis reached the milestones at the same age, with a mean difference of 0.0 months, and girls with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• Relative to boys without atopic dermatitis, boys with self-reported doctor-diagnosed atopic dermatitis reached the milestones a mean of 0.1 month later and boys with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• A more stringent definition of atopic dermatitis — persistent or recurrent atopic dermatitis at 7 years of age (assumed more likely to affect sleep and disrupt the skin barrier near the start of puberty) — was also not associated with delayed pubertal development.

IN PRACTICE:

“Previous studies on atopic dermatitis and puberty are limited, some suggest a link between atopic dermatitis and delayed puberty, akin to other chronic inflammatory diseases in childhood,” the authors wrote. “The results of the present study are reassuring for young patients with atopic dermatitis approaching puberty and reproductive health in adult life,” they concluded.

SOURCE:

The study was led by Camilla Lomholt Kjersgaard, MD, Aarhus University, Aarhus, Denmark, and was published online in JAAD International. 

LIMITATIONS:

Limitations included a lack of information on treatment, the use of analyses that did not address missing data, and a possible misclassification of self-reported pubertal development.

DISCLOSURES:

The study was funded by the Danish Council for Independent Research; Aarhus University; and Fonden af Fam. Kjærsgaard, Sunds; and was cofunded by the European Union. The authors reported no relevant conflicts of interest.

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

TOPLINE:

Children with atopic dermatitis, even of greater severity, do not experience a delay in attaining pubertal milestones.

METHODOLOGY:

• Investigators conducted a nationwide cohort study among 15,534 children in Denmark whose pubertal development was assessed every 6 months with a web-based questionnaire starting at the age of 11 years.
• The children were classified into three groups: No atopic dermatitis; self-reported doctor-diagnosed atopic dermatitis (maternal report of a doctor diagnosis at 6 months, 18 months, and/or 7 years of age); hospital-diagnosed atopic dermatitis (registry data showing it as the primary reason for hospital contact up to the age of 8 years), representing mainly severe cases.
• The main outcome was the age difference averaged across a range of pubertal milestones (attainment of Tanner stages; development of axillary hair, acne, and voice break; and occurrence of first ejaculation and menarche).

TAKEAWAY:

• Overall, 21.5% of the children had self-reported doctor-diagnosed atopic dermatitis and 0.7% had hospital-diagnosed atopic dermatitis.
• Relative to girls without atopic dermatitis, girls with self-reported doctor-diagnosed atopic dermatitis reached the milestones at the same age, with a mean difference of 0.0 months, and girls with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• Relative to boys without atopic dermatitis, boys with self-reported doctor-diagnosed atopic dermatitis reached the milestones a mean of 0.1 month later and boys with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• A more stringent definition of atopic dermatitis — persistent or recurrent atopic dermatitis at 7 years of age (assumed more likely to affect sleep and disrupt the skin barrier near the start of puberty) — was also not associated with delayed pubertal development.

IN PRACTICE:

“Previous studies on atopic dermatitis and puberty are limited, some suggest a link between atopic dermatitis and delayed puberty, akin to other chronic inflammatory diseases in childhood,” the authors wrote. “The results of the present study are reassuring for young patients with atopic dermatitis approaching puberty and reproductive health in adult life,” they concluded.

SOURCE:

The study was led by Camilla Lomholt Kjersgaard, MD, Aarhus University, Aarhus, Denmark, and was published online in JAAD International. 

LIMITATIONS:

Limitations included a lack of information on treatment, the use of analyses that did not address missing data, and a possible misclassification of self-reported pubertal development.

DISCLOSURES:

The study was funded by the Danish Council for Independent Research; Aarhus University; and Fonden af Fam. Kjærsgaard, Sunds; and was cofunded by the European Union. The authors reported no relevant conflicts of interest.

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

TOPLINE:

Children with atopic dermatitis, even of greater severity, do not experience a delay in attaining pubertal milestones.

METHODOLOGY:

• Investigators conducted a nationwide cohort study among 15,534 children in Denmark whose pubertal development was assessed every 6 months with a web-based questionnaire starting at the age of 11 years.
• The children were classified into three groups: No atopic dermatitis; self-reported doctor-diagnosed atopic dermatitis (maternal report of a doctor diagnosis at 6 months, 18 months, and/or 7 years of age); hospital-diagnosed atopic dermatitis (registry data showing it as the primary reason for hospital contact up to the age of 8 years), representing mainly severe cases.
• The main outcome was the age difference averaged across a range of pubertal milestones (attainment of Tanner stages; development of axillary hair, acne, and voice break; and occurrence of first ejaculation and menarche).

TAKEAWAY:

• Overall, 21.5% of the children had self-reported doctor-diagnosed atopic dermatitis and 0.7% had hospital-diagnosed atopic dermatitis.
• Relative to girls without atopic dermatitis, girls with self-reported doctor-diagnosed atopic dermatitis reached the milestones at the same age, with a mean difference of 0.0 months, and girls with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• Relative to boys without atopic dermatitis, boys with self-reported doctor-diagnosed atopic dermatitis reached the milestones a mean of 0.1 month later and boys with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
• A more stringent definition of atopic dermatitis — persistent or recurrent atopic dermatitis at 7 years of age (assumed more likely to affect sleep and disrupt the skin barrier near the start of puberty) — was also not associated with delayed pubertal development.

IN PRACTICE:

“Previous studies on atopic dermatitis and puberty are limited, some suggest a link between atopic dermatitis and delayed puberty, akin to other chronic inflammatory diseases in childhood,” the authors wrote. “The results of the present study are reassuring for young patients with atopic dermatitis approaching puberty and reproductive health in adult life,” they concluded.

SOURCE:

The study was led by Camilla Lomholt Kjersgaard, MD, Aarhus University, Aarhus, Denmark, and was published online in JAAD International. 

LIMITATIONS:

Limitations included a lack of information on treatment, the use of analyses that did not address missing data, and a possible misclassification of self-reported pubertal development.

DISCLOSURES:

The study was funded by the Danish Council for Independent Research; Aarhus University; and Fonden af Fam. Kjærsgaard, Sunds; and was cofunded by the European Union. The authors reported no relevant conflicts of interest.

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

Clinical Scenario

Lilly is a 15-year-old girl in her sophomore year of high school. Over the course of a month after a romantic and then a friend-group breakup, her parents have been concerned about her increasing tearfulness every day and retreat from activities to avoid social interactions with others that she once enjoyed so much. She has been missing more and more school, saying that she can’t bear to go, and staying in bed during the days, even on weekends. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment in 2 weeks with you and then again in another 2 weeks. Her parents and she tell you, “I thought she would be better by now.” You feel stuck with how to proceed in the visit. You have correctly identified the problem as depression, started the recommended evidence-based treatments, but the parents and Lilly are looking to you for something more or different. There are not many or other local resources. When and how do you all determine what “better” looks and feels like? Where do you go from here?

Metrics Can Guide Next Steps

This clinical scenario is not uncommon. As a psychiatrist consultant in primary care, I often encounter the following comment and question: “Someone isn’t feeling better. I have them taking an SSRI and doing psychotherapy. What is the next thing to do?” In discussions with supervisees and in training residents, I often say that you will know that your consultations have made a real impact on providers’ practices when these questions shift from “what’s the next medication or treatment” to a more robust baseline and follow-up inventory of symptoms via common and available metrics (PHQ9A, PSC-17 or 30, SCARED) shared with you at the start, the middle, and at other times of treatment. Such metrics can more meaningfully guide your collaborative clinical discussions and decisions.

Tracking baseline metrics and follow-up with treatment interventions is a transformative approach to clinical care. But, in primary care, it’s common that the question around mental health care may not receive the same robust screening and tracking of symptoms which have the power to more thoughtfully guide decision-making, even though this is common in other forms of patient care which have more routine use of more objective data. 

Measurement-based treatment to target approaches are well-studied, but not often or always implemented. They involve providing a baseline metric (PHQ9A, Pediatric Symptom Checklist 17 or 30, GAD7, or SCARED), and tracking that metric for response over time using specific scores for decision points. 

 

An Alternative Clinical Scenario

Consider the following alternative scenario for the above patient using a measurement-based treatment to target approach:

Lilly is a 15-year-old girl in her sophomore year of high school with symptoms concerning for depression. A PHQ9A is administered in your appointment, and she scores 20 out of 30, exceeding the threshold score for 11 for depression. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment with you in 2 weeks and then again in another 2 weeks. You obtain a PHQ9A at each appointment, and track the change with her and her parents over time. 

You share with her and the family that it is common that there will be fluctuations in measurements, and you know that a score change on the PHQ9A greater than 7 is considered a clinically significant, reliable change. So, a PHQ9 score reduction from 20 to 13 would be meaningful progress. While seeking a score within the normal and non-clinical range, the progress can be tracked in a way that allows a more robust monitoring of treatment response. If the scores do not improve, you can see that and act accordingly. This way of using metrics shifts the conversation from “how are you feeling now and today” to tracking symptoms more broadly and tracking those individual symptoms over time, some of which may improve and some which may be trickier to target. 

Such a way of tracking common mental health symptoms with a focus on having data at baseline and throughout treatment allows a provider to change or adapt interventions, and to not chase something that can feel ephemeral, such as “feeling happy or looking better.” 

For additional information on the measurement-based treatment to target approach, there are resources that share in more depth the research informing this approach, and other and broader real ways to integrate these practices into your own visits:

• Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
• AACAP Clinical Update: Collaborative Mental Health Care for Children and Adolescents in Primary Care 

Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine. 

Clinical Scenario

Lilly is a 15-year-old girl in her sophomore year of high school. Over the course of a month after a romantic and then a friend-group breakup, her parents have been concerned about her increasing tearfulness every day and retreat from activities to avoid social interactions with others that she once enjoyed so much. She has been missing more and more school, saying that she can’t bear to go, and staying in bed during the days, even on weekends. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment in 2 weeks with you and then again in another 2 weeks. Her parents and she tell you, “I thought she would be better by now.” You feel stuck with how to proceed in the visit. You have correctly identified the problem as depression, started the recommended evidence-based treatments, but the parents and Lilly are looking to you for something more or different. There are not many or other local resources. When and how do you all determine what “better” looks and feels like? Where do you go from here?

Metrics Can Guide Next Steps

This clinical scenario is not uncommon. As a psychiatrist consultant in primary care, I often encounter the following comment and question: “Someone isn’t feeling better. I have them taking an SSRI and doing psychotherapy. What is the next thing to do?” In discussions with supervisees and in training residents, I often say that you will know that your consultations have made a real impact on providers’ practices when these questions shift from “what’s the next medication or treatment” to a more robust baseline and follow-up inventory of symptoms via common and available metrics (PHQ9A, PSC-17 or 30, SCARED) shared with you at the start, the middle, and at other times of treatment. Such metrics can more meaningfully guide your collaborative clinical discussions and decisions.

Tracking baseline metrics and follow-up with treatment interventions is a transformative approach to clinical care. But, in primary care, it’s common that the question around mental health care may not receive the same robust screening and tracking of symptoms which have the power to more thoughtfully guide decision-making, even though this is common in other forms of patient care which have more routine use of more objective data. 

Measurement-based treatment to target approaches are well-studied, but not often or always implemented. They involve providing a baseline metric (PHQ9A, Pediatric Symptom Checklist 17 or 30, GAD7, or SCARED), and tracking that metric for response over time using specific scores for decision points. 

 

An Alternative Clinical Scenario

Consider the following alternative scenario for the above patient using a measurement-based treatment to target approach:

Lilly is a 15-year-old girl in her sophomore year of high school with symptoms concerning for depression. A PHQ9A is administered in your appointment, and she scores 20 out of 30, exceeding the threshold score for 11 for depression. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment with you in 2 weeks and then again in another 2 weeks. You obtain a PHQ9A at each appointment, and track the change with her and her parents over time. 

You share with her and the family that it is common that there will be fluctuations in measurements, and you know that a score change on the PHQ9A greater than 7 is considered a clinically significant, reliable change. So, a PHQ9 score reduction from 20 to 13 would be meaningful progress. While seeking a score within the normal and non-clinical range, the progress can be tracked in a way that allows a more robust monitoring of treatment response. If the scores do not improve, you can see that and act accordingly. This way of using metrics shifts the conversation from “how are you feeling now and today” to tracking symptoms more broadly and tracking those individual symptoms over time, some of which may improve and some which may be trickier to target. 

Such a way of tracking common mental health symptoms with a focus on having data at baseline and throughout treatment allows a provider to change or adapt interventions, and to not chase something that can feel ephemeral, such as “feeling happy or looking better.” 

For additional information on the measurement-based treatment to target approach, there are resources that share in more depth the research informing this approach, and other and broader real ways to integrate these practices into your own visits:

• Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
• AACAP Clinical Update: Collaborative Mental Health Care for Children and Adolescents in Primary Care 

Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine. 

Clinical Scenario

Lilly is a 15-year-old girl in her sophomore year of high school. Over the course of a month after a romantic and then a friend-group breakup, her parents have been concerned about her increasing tearfulness every day and retreat from activities to avoid social interactions with others that she once enjoyed so much. She has been missing more and more school, saying that she can’t bear to go, and staying in bed during the days, even on weekends. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment in 2 weeks with you and then again in another 2 weeks. Her parents and she tell you, “I thought she would be better by now.” You feel stuck with how to proceed in the visit. You have correctly identified the problem as depression, started the recommended evidence-based treatments, but the parents and Lilly are looking to you for something more or different. There are not many or other local resources. When and how do you all determine what “better” looks and feels like? Where do you go from here?

Metrics Can Guide Next Steps

This clinical scenario is not uncommon. As a psychiatrist consultant in primary care, I often encounter the following comment and question: “Someone isn’t feeling better. I have them taking an SSRI and doing psychotherapy. What is the next thing to do?” In discussions with supervisees and in training residents, I often say that you will know that your consultations have made a real impact on providers’ practices when these questions shift from “what’s the next medication or treatment” to a more robust baseline and follow-up inventory of symptoms via common and available metrics (PHQ9A, PSC-17 or 30, SCARED) shared with you at the start, the middle, and at other times of treatment. Such metrics can more meaningfully guide your collaborative clinical discussions and decisions.

Tracking baseline metrics and follow-up with treatment interventions is a transformative approach to clinical care. But, in primary care, it’s common that the question around mental health care may not receive the same robust screening and tracking of symptoms which have the power to more thoughtfully guide decision-making, even though this is common in other forms of patient care which have more routine use of more objective data. 

Measurement-based treatment to target approaches are well-studied, but not often or always implemented. They involve providing a baseline metric (PHQ9A, Pediatric Symptom Checklist 17 or 30, GAD7, or SCARED), and tracking that metric for response over time using specific scores for decision points. 

 

An Alternative Clinical Scenario

Consider the following alternative scenario for the above patient using a measurement-based treatment to target approach:

Lilly is a 15-year-old girl in her sophomore year of high school with symptoms concerning for depression. A PHQ9A is administered in your appointment, and she scores 20 out of 30, exceeding the threshold score for 11 for depression. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment with you in 2 weeks and then again in another 2 weeks. You obtain a PHQ9A at each appointment, and track the change with her and her parents over time. 

You share with her and the family that it is common that there will be fluctuations in measurements, and you know that a score change on the PHQ9A greater than 7 is considered a clinically significant, reliable change. So, a PHQ9 score reduction from 20 to 13 would be meaningful progress. While seeking a score within the normal and non-clinical range, the progress can be tracked in a way that allows a more robust monitoring of treatment response. If the scores do not improve, you can see that and act accordingly. This way of using metrics shifts the conversation from “how are you feeling now and today” to tracking symptoms more broadly and tracking those individual symptoms over time, some of which may improve and some which may be trickier to target. 

Such a way of tracking common mental health symptoms with a focus on having data at baseline and throughout treatment allows a provider to change or adapt interventions, and to not chase something that can feel ephemeral, such as “feeling happy or looking better.” 

For additional information on the measurement-based treatment to target approach, there are resources that share in more depth the research informing this approach, and other and broader real ways to integrate these practices into your own visits:

• Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
• AACAP Clinical Update: Collaborative Mental Health Care for Children and Adolescents in Primary Care 

Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine. 

Understanding how people make health-related decisions requires a deeper exploration of their motivations, beliefs, and circumstances, Christopher Dye, DPhil, professor of epidemiology at the University of Oxford in England, and former director of strategy at the World Health Organization, said in an interview. “In public health, we tend to prescribe solutions. But unless we understand how people really make choices about health and why they are less interested in prevention and happier to wait until they become ill, then we are not in the position to shift away from curative treatments to preventive treatments.”

Despite the well-documented benefits of preventive measures, many people fail to engage in proactive health behaviors. This can be attributed to psychological biases and socioeconomic factors that shape how people prioritize their health.

“The choices people make have some to do with facts, but they also have much to do with values and perception. We need to understand and take these perceptions and values seriously,” Dye said.

 

The Paradox of Prevention

People often recognize prevention as the right course of action but fail to act. “We know it’s the right thing to do, but we don’t do it,” Dye said.

He explained that, when considering potential future threats, we assess two key factors: The severity of the danger and the cost of addressing it. Action is more likely when the danger is significant and the cost of mitigation is low.

This dynamic can be broken down into three critical questions:

What is the nature of the hazard? Is the threat severe, like Ebola, which has a case fatality rate of around 50% in untreated cases, or relatively milder, like COVID-19, with a fatality rate of less than 1% but a much broader spread? The nastier the hazard, the more likely we are to take it seriously.

How likely is it to happen? Even a severe threat will not prompt much concern if its likelihood is perceived as low. Our willingness to act depends heavily on how probable people think the hazard is.

When is it likely to happen? A threat looming in the immediate future is more compelling than one projected weeks, months, or years away. This is because people tend to heavily discount the value of future risks.

When these factors — severity, likelihood, and immediacy — combine with low mitigation costs, the incentives for action align.

However, cost is not limited to financial expense. It encompasses effort, willpower, access to information, and personal inclination. Similarly, the perception of threat is shaped not just by hard data and epidemiology but also by subjective values and cultural interpretations.

“We place a high value on now rather than later,” Theresa Marteau, PhD, a psychologist and behavioral scientist and director of the Behaviour and Health Research Unit at the University of Cambridge in England, said in an interview. “Treatment is about fixing a problem that we have now, rather than trying to avoid a problem sometime in the future. We also place a high value on certainty: I’m ill today, and I want to avoid that, as opposed to putting resources on a possible disease that might or might not occur.”

 

Investing in the Future: A Privilege of Stability

People often undervalue future health risks because of temporal discounting, a cognitive bias where immediate rewards are prioritized over long-term benefits. This tendency makes it challenging to address health issues that may only manifest years later.

From a public health perspective, this creates challenges. Warning individuals that harmful behaviors, such as smoking, may lead to severe health problems in a decade often falls on deaf ears. People naturally focus on immediate concerns, particularly when grappling with present challenges. For those living in poverty or social instability, the urgency of daily survival frequently outweighs the perceived benefits of preventive health measures.

“A cigarette during the day is just one brief source of pleasure, a short-term escape from all the other stuff happening in their lives, and there’s more of that stuff happening to poorer people than there is to richer people,” Dye said.

He said that long-term thinking comes more naturally to those with stability and resources. People who are financially secure, have stable jobs, supportive families, and comfortable homes are better equipped to invest for the future and prioritize their health.

“People value their health regardless of their social and economic circumstances,” said Marteau. “But they might not have the resources to engage in behavior-changing activities.”

 

Bringing the Future to the Present

Effective interventions often involve a combination of “sticks” (deterrents) and “carrots” (rewards), Dye explained. Both approaches aim to bridge the gap between immediate actions and future benefits by making preventive behaviors more appealing in the short term. “We need to bring the future into the present,” he added.

Raising the cost of unhealthy behaviors has proven effective. For example, increasing the price of cigarettes leads to significant reductions in smoking rates. When smoking becomes less affordable, individuals are more likely to quit. Dye said that this approach works to a certain extent. At some point, the number of people quitting plateaus and those from low socioeconomic backgrounds are those more likely to continue to smoke.

Offering immediate rewards for preventive behaviors provides a powerful incentive. Things that give tangible benefits, like attending regular health checkups, receiving vaccinations, or joining fitness programs, can motivate individuals to engage in health-preserving activities. “The key is ensuring these benefits are timely and meaningful, as delayed rewards are less effective in overcoming the natural bias toward the present,” said Dye.

Healthcare providers are best placed to help people engage in preventive behavior by referring patients to the right services, such as programs to stop smoking, weight loss programs and medications, or mental health providers, Marteau said. “It’s not telling people to stop smoking or change their diet. It’s about signposting them to effective services that will help them change their behavior.”

Dye and Marteau reported no relevant financial relationships.

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

Understanding how people make health-related decisions requires a deeper exploration of their motivations, beliefs, and circumstances, Christopher Dye, DPhil, professor of epidemiology at the University of Oxford in England, and former director of strategy at the World Health Organization, said in an interview. “In public health, we tend to prescribe solutions. But unless we understand how people really make choices about health and why they are less interested in prevention and happier to wait until they become ill, then we are not in the position to shift away from curative treatments to preventive treatments.”

Despite the well-documented benefits of preventive measures, many people fail to engage in proactive health behaviors. This can be attributed to psychological biases and socioeconomic factors that shape how people prioritize their health.

“The choices people make have some to do with facts, but they also have much to do with values and perception. We need to understand and take these perceptions and values seriously,” Dye said.

 

The Paradox of Prevention

People often recognize prevention as the right course of action but fail to act. “We know it’s the right thing to do, but we don’t do it,” Dye said.

He explained that, when considering potential future threats, we assess two key factors: The severity of the danger and the cost of addressing it. Action is more likely when the danger is significant and the cost of mitigation is low.

This dynamic can be broken down into three critical questions:

What is the nature of the hazard? Is the threat severe, like Ebola, which has a case fatality rate of around 50% in untreated cases, or relatively milder, like COVID-19, with a fatality rate of less than 1% but a much broader spread? The nastier the hazard, the more likely we are to take it seriously.

How likely is it to happen? Even a severe threat will not prompt much concern if its likelihood is perceived as low. Our willingness to act depends heavily on how probable people think the hazard is.

When is it likely to happen? A threat looming in the immediate future is more compelling than one projected weeks, months, or years away. This is because people tend to heavily discount the value of future risks.

When these factors — severity, likelihood, and immediacy — combine with low mitigation costs, the incentives for action align.

However, cost is not limited to financial expense. It encompasses effort, willpower, access to information, and personal inclination. Similarly, the perception of threat is shaped not just by hard data and epidemiology but also by subjective values and cultural interpretations.

“We place a high value on now rather than later,” Theresa Marteau, PhD, a psychologist and behavioral scientist and director of the Behaviour and Health Research Unit at the University of Cambridge in England, said in an interview. “Treatment is about fixing a problem that we have now, rather than trying to avoid a problem sometime in the future. We also place a high value on certainty: I’m ill today, and I want to avoid that, as opposed to putting resources on a possible disease that might or might not occur.”

 

Investing in the Future: A Privilege of Stability

People often undervalue future health risks because of temporal discounting, a cognitive bias where immediate rewards are prioritized over long-term benefits. This tendency makes it challenging to address health issues that may only manifest years later.

From a public health perspective, this creates challenges. Warning individuals that harmful behaviors, such as smoking, may lead to severe health problems in a decade often falls on deaf ears. People naturally focus on immediate concerns, particularly when grappling with present challenges. For those living in poverty or social instability, the urgency of daily survival frequently outweighs the perceived benefits of preventive health measures.

“A cigarette during the day is just one brief source of pleasure, a short-term escape from all the other stuff happening in their lives, and there’s more of that stuff happening to poorer people than there is to richer people,” Dye said.

He said that long-term thinking comes more naturally to those with stability and resources. People who are financially secure, have stable jobs, supportive families, and comfortable homes are better equipped to invest for the future and prioritize their health.

“People value their health regardless of their social and economic circumstances,” said Marteau. “But they might not have the resources to engage in behavior-changing activities.”

 

Bringing the Future to the Present

Effective interventions often involve a combination of “sticks” (deterrents) and “carrots” (rewards), Dye explained. Both approaches aim to bridge the gap between immediate actions and future benefits by making preventive behaviors more appealing in the short term. “We need to bring the future into the present,” he added.

Raising the cost of unhealthy behaviors has proven effective. For example, increasing the price of cigarettes leads to significant reductions in smoking rates. When smoking becomes less affordable, individuals are more likely to quit. Dye said that this approach works to a certain extent. At some point, the number of people quitting plateaus and those from low socioeconomic backgrounds are those more likely to continue to smoke.

Offering immediate rewards for preventive behaviors provides a powerful incentive. Things that give tangible benefits, like attending regular health checkups, receiving vaccinations, or joining fitness programs, can motivate individuals to engage in health-preserving activities. “The key is ensuring these benefits are timely and meaningful, as delayed rewards are less effective in overcoming the natural bias toward the present,” said Dye.

Healthcare providers are best placed to help people engage in preventive behavior by referring patients to the right services, such as programs to stop smoking, weight loss programs and medications, or mental health providers, Marteau said. “It’s not telling people to stop smoking or change their diet. It’s about signposting them to effective services that will help them change their behavior.”

Dye and Marteau reported no relevant financial relationships.

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

Understanding how people make health-related decisions requires a deeper exploration of their motivations, beliefs, and circumstances, Christopher Dye, DPhil, professor of epidemiology at the University of Oxford in England, and former director of strategy at the World Health Organization, said in an interview. “In public health, we tend to prescribe solutions. But unless we understand how people really make choices about health and why they are less interested in prevention and happier to wait until they become ill, then we are not in the position to shift away from curative treatments to preventive treatments.”

Despite the well-documented benefits of preventive measures, many people fail to engage in proactive health behaviors. This can be attributed to psychological biases and socioeconomic factors that shape how people prioritize their health.

“The choices people make have some to do with facts, but they also have much to do with values and perception. We need to understand and take these perceptions and values seriously,” Dye said.

 

The Paradox of Prevention

People often recognize prevention as the right course of action but fail to act. “We know it’s the right thing to do, but we don’t do it,” Dye said.

He explained that, when considering potential future threats, we assess two key factors: The severity of the danger and the cost of addressing it. Action is more likely when the danger is significant and the cost of mitigation is low.

This dynamic can be broken down into three critical questions:

What is the nature of the hazard? Is the threat severe, like Ebola, which has a case fatality rate of around 50% in untreated cases, or relatively milder, like COVID-19, with a fatality rate of less than 1% but a much broader spread? The nastier the hazard, the more likely we are to take it seriously.

How likely is it to happen? Even a severe threat will not prompt much concern if its likelihood is perceived as low. Our willingness to act depends heavily on how probable people think the hazard is.

When is it likely to happen? A threat looming in the immediate future is more compelling than one projected weeks, months, or years away. This is because people tend to heavily discount the value of future risks.

When these factors — severity, likelihood, and immediacy — combine with low mitigation costs, the incentives for action align.

However, cost is not limited to financial expense. It encompasses effort, willpower, access to information, and personal inclination. Similarly, the perception of threat is shaped not just by hard data and epidemiology but also by subjective values and cultural interpretations.

“We place a high value on now rather than later,” Theresa Marteau, PhD, a psychologist and behavioral scientist and director of the Behaviour and Health Research Unit at the University of Cambridge in England, said in an interview. “Treatment is about fixing a problem that we have now, rather than trying to avoid a problem sometime in the future. We also place a high value on certainty: I’m ill today, and I want to avoid that, as opposed to putting resources on a possible disease that might or might not occur.”

 

Investing in the Future: A Privilege of Stability

People often undervalue future health risks because of temporal discounting, a cognitive bias where immediate rewards are prioritized over long-term benefits. This tendency makes it challenging to address health issues that may only manifest years later.

From a public health perspective, this creates challenges. Warning individuals that harmful behaviors, such as smoking, may lead to severe health problems in a decade often falls on deaf ears. People naturally focus on immediate concerns, particularly when grappling with present challenges. For those living in poverty or social instability, the urgency of daily survival frequently outweighs the perceived benefits of preventive health measures.

“A cigarette during the day is just one brief source of pleasure, a short-term escape from all the other stuff happening in their lives, and there’s more of that stuff happening to poorer people than there is to richer people,” Dye said.

He said that long-term thinking comes more naturally to those with stability and resources. People who are financially secure, have stable jobs, supportive families, and comfortable homes are better equipped to invest for the future and prioritize their health.

“People value their health regardless of their social and economic circumstances,” said Marteau. “But they might not have the resources to engage in behavior-changing activities.”

 

Bringing the Future to the Present

Effective interventions often involve a combination of “sticks” (deterrents) and “carrots” (rewards), Dye explained. Both approaches aim to bridge the gap between immediate actions and future benefits by making preventive behaviors more appealing in the short term. “We need to bring the future into the present,” he added.

Raising the cost of unhealthy behaviors has proven effective. For example, increasing the price of cigarettes leads to significant reductions in smoking rates. When smoking becomes less affordable, individuals are more likely to quit. Dye said that this approach works to a certain extent. At some point, the number of people quitting plateaus and those from low socioeconomic backgrounds are those more likely to continue to smoke.

Offering immediate rewards for preventive behaviors provides a powerful incentive. Things that give tangible benefits, like attending regular health checkups, receiving vaccinations, or joining fitness programs, can motivate individuals to engage in health-preserving activities. “The key is ensuring these benefits are timely and meaningful, as delayed rewards are less effective in overcoming the natural bias toward the present,” said Dye.

Healthcare providers are best placed to help people engage in preventive behavior by referring patients to the right services, such as programs to stop smoking, weight loss programs and medications, or mental health providers, Marteau said. “It’s not telling people to stop smoking or change their diet. It’s about signposting them to effective services that will help them change their behavior.”

Dye and Marteau reported no relevant financial relationships.

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

Chronic exposure to glyphosate — the most widely used herbicide globally — may be a risk factor for Alzheimer’s disease, new research showed. 

Researchers found that glyphosate exposure even at regulated levels was associated with increased neuroinflammation and accelerated Alzheimer’s disease–like pathology in mice — an effect that persisted 6 months after a recovery period when exposure was stopped.

“More research is needed to understand the consequences of glyphosate exposure to the brain in humans and to understand the appropriate dose of exposure to limit detrimental outcomes,” said co–senior author Ramon Velazquez, PhD, with Arizona State University, Tempe.

The study was published online in The Journal of Neuroinflammation.

 

Persistent Accumulation Within the Brain

Glyphosate is the most heavily applied herbicide in the United States, with roughly 300 million pounds used annually in agricultural communities throughout the United States. It is also used for weed control in parks, residential areas, and personal gardens.

The Environmental Protection Agency (EPA) has determined that glyphosate poses no risks to human health when used as directed. But the World Health Organization’s International Agency for Research on Cancer disagrees, classifying the herbicide as “possibly carcinogenic to humans.”

In addition to the possible cancer risk, multiple reports have also suggested potential harmful effects of glyphosate exposure on the brain. 

In earlier work, Velazquez and colleagues showed that glyphosate crosses the blood-brain barrier and infiltrates the brains of mice, contributing to neuroinflammation and other detrimental effects on brain function. 

In their latest study, they examined the long-term effects of glyphosate exposure on neuroinflammation and Alzheimer’s disease–like pathology using a mouse model.

They dosed 4.5-month-old mice genetically predisposed to Alzheimer’s disease and non-transgenic control mice with either 0, 50, or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period. 

The high dose is similar to levels used in earlier research, and the low dose is close to the limit used to establish the current EPA acceptable dose in humans.

Glyphosate’s metabolite, aminomethylphosphonic acid, was detectable and persisted in mouse brain tissue even 6 months after exposure ceased, the researchers reported. 

Additionally, there was a significant increase in soluble and insoluble fractions of amyloid-beta (Abeta), Abeta42 plaque load and plaque size, and phosphorylated tau at Threonine 181 and Serine 396 in hippocampus and cortex brain tissue from glyphosate-exposed mice, “highlighting an exacerbation of hallmark Alzheimer’s disease–like proteinopathies,” they noted. 

Glyphosate exposure was also associated with significant elevations in both pro- and anti-inflammatory cytokines and chemokines in brain tissue of transgenic and normal mice and in peripheral blood plasma of transgenic mice. 

Glyphosate-exposed transgenic mice also showed heightened anxiety-like behaviors and reduced survival. 

“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks,” co–senior author Patrick Pirrotte, PhD, with the Translational Genomics Research Institute, Phoenix, Arizona, said in a statement.

“However, further research is needed to fully assess the public health impact and identify safer alternatives,” Pirrotte added. 

Funding for the study was provided by the National Institutes on Aging, National Cancer Institute and the Arizona State University (ASU) Biodesign Institute. The authors have declared no relevant conflicts of interest.

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

Chronic exposure to glyphosate — the most widely used herbicide globally — may be a risk factor for Alzheimer’s disease, new research showed. 

Researchers found that glyphosate exposure even at regulated levels was associated with increased neuroinflammation and accelerated Alzheimer’s disease–like pathology in mice — an effect that persisted 6 months after a recovery period when exposure was stopped.

“More research is needed to understand the consequences of glyphosate exposure to the brain in humans and to understand the appropriate dose of exposure to limit detrimental outcomes,” said co–senior author Ramon Velazquez, PhD, with Arizona State University, Tempe.

The study was published online in The Journal of Neuroinflammation.

 

Persistent Accumulation Within the Brain

Glyphosate is the most heavily applied herbicide in the United States, with roughly 300 million pounds used annually in agricultural communities throughout the United States. It is also used for weed control in parks, residential areas, and personal gardens.

The Environmental Protection Agency (EPA) has determined that glyphosate poses no risks to human health when used as directed. But the World Health Organization’s International Agency for Research on Cancer disagrees, classifying the herbicide as “possibly carcinogenic to humans.”

In addition to the possible cancer risk, multiple reports have also suggested potential harmful effects of glyphosate exposure on the brain. 

In earlier work, Velazquez and colleagues showed that glyphosate crosses the blood-brain barrier and infiltrates the brains of mice, contributing to neuroinflammation and other detrimental effects on brain function. 

In their latest study, they examined the long-term effects of glyphosate exposure on neuroinflammation and Alzheimer’s disease–like pathology using a mouse model.

They dosed 4.5-month-old mice genetically predisposed to Alzheimer’s disease and non-transgenic control mice with either 0, 50, or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period. 

The high dose is similar to levels used in earlier research, and the low dose is close to the limit used to establish the current EPA acceptable dose in humans.

Glyphosate’s metabolite, aminomethylphosphonic acid, was detectable and persisted in mouse brain tissue even 6 months after exposure ceased, the researchers reported. 

Additionally, there was a significant increase in soluble and insoluble fractions of amyloid-beta (Abeta), Abeta42 plaque load and plaque size, and phosphorylated tau at Threonine 181 and Serine 396 in hippocampus and cortex brain tissue from glyphosate-exposed mice, “highlighting an exacerbation of hallmark Alzheimer’s disease–like proteinopathies,” they noted. 

Glyphosate exposure was also associated with significant elevations in both pro- and anti-inflammatory cytokines and chemokines in brain tissue of transgenic and normal mice and in peripheral blood plasma of transgenic mice. 

Glyphosate-exposed transgenic mice also showed heightened anxiety-like behaviors and reduced survival. 

“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks,” co–senior author Patrick Pirrotte, PhD, with the Translational Genomics Research Institute, Phoenix, Arizona, said in a statement.

“However, further research is needed to fully assess the public health impact and identify safer alternatives,” Pirrotte added. 

Funding for the study was provided by the National Institutes on Aging, National Cancer Institute and the Arizona State University (ASU) Biodesign Institute. The authors have declared no relevant conflicts of interest.

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

Chronic exposure to glyphosate — the most widely used herbicide globally — may be a risk factor for Alzheimer’s disease, new research showed. 

Researchers found that glyphosate exposure even at regulated levels was associated with increased neuroinflammation and accelerated Alzheimer’s disease–like pathology in mice — an effect that persisted 6 months after a recovery period when exposure was stopped.

“More research is needed to understand the consequences of glyphosate exposure to the brain in humans and to understand the appropriate dose of exposure to limit detrimental outcomes,” said co–senior author Ramon Velazquez, PhD, with Arizona State University, Tempe.

The study was published online in The Journal of Neuroinflammation.

 

Persistent Accumulation Within the Brain

Glyphosate is the most heavily applied herbicide in the United States, with roughly 300 million pounds used annually in agricultural communities throughout the United States. It is also used for weed control in parks, residential areas, and personal gardens.

The Environmental Protection Agency (EPA) has determined that glyphosate poses no risks to human health when used as directed. But the World Health Organization’s International Agency for Research on Cancer disagrees, classifying the herbicide as “possibly carcinogenic to humans.”

In addition to the possible cancer risk, multiple reports have also suggested potential harmful effects of glyphosate exposure on the brain. 

In earlier work, Velazquez and colleagues showed that glyphosate crosses the blood-brain barrier and infiltrates the brains of mice, contributing to neuroinflammation and other detrimental effects on brain function. 

In their latest study, they examined the long-term effects of glyphosate exposure on neuroinflammation and Alzheimer’s disease–like pathology using a mouse model.

They dosed 4.5-month-old mice genetically predisposed to Alzheimer’s disease and non-transgenic control mice with either 0, 50, or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period. 

The high dose is similar to levels used in earlier research, and the low dose is close to the limit used to establish the current EPA acceptable dose in humans.

Glyphosate’s metabolite, aminomethylphosphonic acid, was detectable and persisted in mouse brain tissue even 6 months after exposure ceased, the researchers reported. 

Additionally, there was a significant increase in soluble and insoluble fractions of amyloid-beta (Abeta), Abeta42 plaque load and plaque size, and phosphorylated tau at Threonine 181 and Serine 396 in hippocampus and cortex brain tissue from glyphosate-exposed mice, “highlighting an exacerbation of hallmark Alzheimer’s disease–like proteinopathies,” they noted. 

Glyphosate exposure was also associated with significant elevations in both pro- and anti-inflammatory cytokines and chemokines in brain tissue of transgenic and normal mice and in peripheral blood plasma of transgenic mice. 

Glyphosate-exposed transgenic mice also showed heightened anxiety-like behaviors and reduced survival. 

“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks,” co–senior author Patrick Pirrotte, PhD, with the Translational Genomics Research Institute, Phoenix, Arizona, said in a statement.

“However, further research is needed to fully assess the public health impact and identify safer alternatives,” Pirrotte added. 

Funding for the study was provided by the National Institutes on Aging, National Cancer Institute and the Arizona State University (ASU) Biodesign Institute. The authors have declared no relevant conflicts of interest.

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