MDedge Endocrinology

TOPLINE:

Once-weekly insulin icodec shows a higher glycated A1c reduction than once-daily basal insulin analogs in patients with type 2 diabetes (T2D), without major safety concerns.

METHODOLOGY:

• A meta-analysis of five phase 3 ONWARDS randomized controlled trials included 3764 patients with T2D.
• The trials compared the effects of the weekly insulin icodec with those of the daily basal insulin analogs glargine and degludec over 26-78 months.
• The primary outcome was the change in A1c levels.
• Secondary outcomes included fasting plasma glucose levels, A1c levels < 7%, time in target glycemic range, body weight changes, insulin dose, hypoglycemia events, and adverse events.

TAKEAWAY:

• A1c levels < 7% were observed in a higher percentage of patients in the insulin icodec group than in the comparator group (odds ratio, 1.51; P = .004).
• In subgroup analyses, insulin icodec was superior to insulin degludec by several measures but comparatively similar to glargine.
• Insulin icodec was associated with no major safety concerns and had a slightly higher incidence of levels 1, 2, and combined 2/3 than degludec but no significant differences compared with glargine.

IN PRACTICE:

“Sustained glycemic control with once-weekly injections of insulin icodec would lead to better patient acceptance and treatment satisfaction,” the authors wrote.

SOURCE:

This study, authored by Sahana Shetty, MD, and Renuka Suvarna, MSc, Manipal Academy of Higher Education, Department of Endocrinology, Kasturba Medical College, Manipal, Karnataka, was published online on January 8, 2024, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The comparator group included individuals who used different basal insulin analogs. This heterogeneity in the comparator group introduced a potential source of variability, making it challenging to isolate the specific effects of insulin icodec compared with a standardized comparator. Blinding or masking of participants was performed in only one of the five trials.

DISCLOSURES:

The authors declared no conflicts of interest. All five clinical trials in the meta-analysis were sponsored by Novo Nordisk.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Once-weekly insulin icodec shows a higher glycated A1c reduction than once-daily basal insulin analogs in patients with type 2 diabetes (T2D), without major safety concerns.

METHODOLOGY:

• A meta-analysis of five phase 3 ONWARDS randomized controlled trials included 3764 patients with T2D.
• The trials compared the effects of the weekly insulin icodec with those of the daily basal insulin analogs glargine and degludec over 26-78 months.
• The primary outcome was the change in A1c levels.
• Secondary outcomes included fasting plasma glucose levels, A1c levels < 7%, time in target glycemic range, body weight changes, insulin dose, hypoglycemia events, and adverse events.

TAKEAWAY:

• A1c levels < 7% were observed in a higher percentage of patients in the insulin icodec group than in the comparator group (odds ratio, 1.51; P = .004).
• In subgroup analyses, insulin icodec was superior to insulin degludec by several measures but comparatively similar to glargine.
• Insulin icodec was associated with no major safety concerns and had a slightly higher incidence of levels 1, 2, and combined 2/3 than degludec but no significant differences compared with glargine.

IN PRACTICE:

“Sustained glycemic control with once-weekly injections of insulin icodec would lead to better patient acceptance and treatment satisfaction,” the authors wrote.

SOURCE:

This study, authored by Sahana Shetty, MD, and Renuka Suvarna, MSc, Manipal Academy of Higher Education, Department of Endocrinology, Kasturba Medical College, Manipal, Karnataka, was published online on January 8, 2024, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The comparator group included individuals who used different basal insulin analogs. This heterogeneity in the comparator group introduced a potential source of variability, making it challenging to isolate the specific effects of insulin icodec compared with a standardized comparator. Blinding or masking of participants was performed in only one of the five trials.

DISCLOSURES:

The authors declared no conflicts of interest. All five clinical trials in the meta-analysis were sponsored by Novo Nordisk.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Once-weekly insulin icodec shows a higher glycated A1c reduction than once-daily basal insulin analogs in patients with type 2 diabetes (T2D), without major safety concerns.

METHODOLOGY:

• A meta-analysis of five phase 3 ONWARDS randomized controlled trials included 3764 patients with T2D.
• The trials compared the effects of the weekly insulin icodec with those of the daily basal insulin analogs glargine and degludec over 26-78 months.
• The primary outcome was the change in A1c levels.
• Secondary outcomes included fasting plasma glucose levels, A1c levels < 7%, time in target glycemic range, body weight changes, insulin dose, hypoglycemia events, and adverse events.

TAKEAWAY:

• A1c levels < 7% were observed in a higher percentage of patients in the insulin icodec group than in the comparator group (odds ratio, 1.51; P = .004).
• In subgroup analyses, insulin icodec was superior to insulin degludec by several measures but comparatively similar to glargine.
• Insulin icodec was associated with no major safety concerns and had a slightly higher incidence of levels 1, 2, and combined 2/3 than degludec but no significant differences compared with glargine.

IN PRACTICE:

“Sustained glycemic control with once-weekly injections of insulin icodec would lead to better patient acceptance and treatment satisfaction,” the authors wrote.

SOURCE:

This study, authored by Sahana Shetty, MD, and Renuka Suvarna, MSc, Manipal Academy of Higher Education, Department of Endocrinology, Kasturba Medical College, Manipal, Karnataka, was published online on January 8, 2024, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The comparator group included individuals who used different basal insulin analogs. This heterogeneity in the comparator group introduced a potential source of variability, making it challenging to isolate the specific effects of insulin icodec compared with a standardized comparator. Blinding or masking of participants was performed in only one of the five trials.

DISCLOSURES:

The authors declared no conflicts of interest. All five clinical trials in the meta-analysis were sponsored by Novo Nordisk.
 

A version of this article appeared on Medscape.com.

A recent study sheds light on the heightened risk for burnout among physicians who take infrequent vacations and engage in patient-related work during their time off.

Conducted by the American Medical Association (AMA), the study focuses on the United States, where labor regulations regarding vacation days and compensation differ from German norms. Despite this distinction, it provides valuable insights into the vacation behavior of doctors and its potential impact on burnout risk.

Christine A. Sinsky, MD, study author and senior physician advisor for physician satisfaction at the AMA, and her colleagues invited more than 90,000 physicians to participate in a survey that used postal and computer-based methods. In all, 3024 physicians, mainly those contacted by mail, filled out the questionnaire.
 

Limited Vacation Days

A significant proportion (59.6%) of respondents reported having taken fewer than 15 vacation days in the previous year, with nearly 20% taking fewer than 5 days off. Even when officially on vacation, most (70.4%) found themselves dealing with patient-related tasks. For one-third, these tasks consumed at least 30 minutes on a typical vacation day, often longer. This phenomenon was noted especially among female physicians.

Doctors who took less vacation and worked during their time off displayed higher emotional exhaustion and reported feeling less fulfilled in their profession.
 

Administrative Tasks 

Administrative tasks, though no longer confined to paper, significantly influenced physicians’ vacation behavior. In the United States, handling messages from patients through the electronic health records (EHR) inbox demands a considerable amount of time.

Courses and tutorials on EHR inbox management are on the rise. A 2023 review linked electronic health records management to an increased burnout risk in the US medical community.
 

Lack of Coverage 

Many physicians lack coverage for their EHR inbox during their absence. Less than half (49.1%) stated that someone else manages their inbox while they are on vacation.

Difficulty in finding coverage, whether for the EHR inbox or patient care, is a leading reason why many physicians seldom take more than 3 weeks of vacation per year. Financial considerations also contribute to this decision, as revealed in the survey.
 

Vacation Lowers Risk

Further analysis showed that doctors who took more than 3 weeks of vacation per year, which is not common, had a lower risk of developing burnout. Having coverage for vacation was also associated with reduced burnout risk and increased professional fulfillment.

However, these benefits applied only when physicians truly took a break during their vacation. Respondents who spent 30 minutes or more per day on patient-related work had a higher burnout risk. The risk was 1.58 times greater for 30-60 minutes, 1.97 times greater for 60-90 minutes, and 1.92 times greater for more than 90 minutes.
 

System-Level Interventions

The vacation behavior observed in this study likely exacerbates the effects of chronic workplace overload that are associated with long working hours, thus increasing the risk for burnout, according to the researchers.

“System-level measures must be implemented to ensure physicians take an appropriate number of vacation days,” wrote the researchers. “This includes having coverage available to handle clinical activities and administrative tasks, such as managing the EHR inbox. This could potentially reduce the burnout rate among physicians.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

A recent study sheds light on the heightened risk for burnout among physicians who take infrequent vacations and engage in patient-related work during their time off.

Conducted by the American Medical Association (AMA), the study focuses on the United States, where labor regulations regarding vacation days and compensation differ from German norms. Despite this distinction, it provides valuable insights into the vacation behavior of doctors and its potential impact on burnout risk.

Christine A. Sinsky, MD, study author and senior physician advisor for physician satisfaction at the AMA, and her colleagues invited more than 90,000 physicians to participate in a survey that used postal and computer-based methods. In all, 3024 physicians, mainly those contacted by mail, filled out the questionnaire.
 

Limited Vacation Days

A significant proportion (59.6%) of respondents reported having taken fewer than 15 vacation days in the previous year, with nearly 20% taking fewer than 5 days off. Even when officially on vacation, most (70.4%) found themselves dealing with patient-related tasks. For one-third, these tasks consumed at least 30 minutes on a typical vacation day, often longer. This phenomenon was noted especially among female physicians.

Doctors who took less vacation and worked during their time off displayed higher emotional exhaustion and reported feeling less fulfilled in their profession.
 

Administrative Tasks 

Administrative tasks, though no longer confined to paper, significantly influenced physicians’ vacation behavior. In the United States, handling messages from patients through the electronic health records (EHR) inbox demands a considerable amount of time.

Courses and tutorials on EHR inbox management are on the rise. A 2023 review linked electronic health records management to an increased burnout risk in the US medical community.
 

Lack of Coverage 

Many physicians lack coverage for their EHR inbox during their absence. Less than half (49.1%) stated that someone else manages their inbox while they are on vacation.

Difficulty in finding coverage, whether for the EHR inbox or patient care, is a leading reason why many physicians seldom take more than 3 weeks of vacation per year. Financial considerations also contribute to this decision, as revealed in the survey.
 

Vacation Lowers Risk

Further analysis showed that doctors who took more than 3 weeks of vacation per year, which is not common, had a lower risk of developing burnout. Having coverage for vacation was also associated with reduced burnout risk and increased professional fulfillment.

However, these benefits applied only when physicians truly took a break during their vacation. Respondents who spent 30 minutes or more per day on patient-related work had a higher burnout risk. The risk was 1.58 times greater for 30-60 minutes, 1.97 times greater for 60-90 minutes, and 1.92 times greater for more than 90 minutes.
 

System-Level Interventions

The vacation behavior observed in this study likely exacerbates the effects of chronic workplace overload that are associated with long working hours, thus increasing the risk for burnout, according to the researchers.

“System-level measures must be implemented to ensure physicians take an appropriate number of vacation days,” wrote the researchers. “This includes having coverage available to handle clinical activities and administrative tasks, such as managing the EHR inbox. This could potentially reduce the burnout rate among physicians.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

A recent study sheds light on the heightened risk for burnout among physicians who take infrequent vacations and engage in patient-related work during their time off.

Conducted by the American Medical Association (AMA), the study focuses on the United States, where labor regulations regarding vacation days and compensation differ from German norms. Despite this distinction, it provides valuable insights into the vacation behavior of doctors and its potential impact on burnout risk.

Christine A. Sinsky, MD, study author and senior physician advisor for physician satisfaction at the AMA, and her colleagues invited more than 90,000 physicians to participate in a survey that used postal and computer-based methods. In all, 3024 physicians, mainly those contacted by mail, filled out the questionnaire.
 

Limited Vacation Days

A significant proportion (59.6%) of respondents reported having taken fewer than 15 vacation days in the previous year, with nearly 20% taking fewer than 5 days off. Even when officially on vacation, most (70.4%) found themselves dealing with patient-related tasks. For one-third, these tasks consumed at least 30 minutes on a typical vacation day, often longer. This phenomenon was noted especially among female physicians.

Doctors who took less vacation and worked during their time off displayed higher emotional exhaustion and reported feeling less fulfilled in their profession.
 

Administrative Tasks 

Administrative tasks, though no longer confined to paper, significantly influenced physicians’ vacation behavior. In the United States, handling messages from patients through the electronic health records (EHR) inbox demands a considerable amount of time.

Courses and tutorials on EHR inbox management are on the rise. A 2023 review linked electronic health records management to an increased burnout risk in the US medical community.
 

Lack of Coverage 

Many physicians lack coverage for their EHR inbox during their absence. Less than half (49.1%) stated that someone else manages their inbox while they are on vacation.

Difficulty in finding coverage, whether for the EHR inbox or patient care, is a leading reason why many physicians seldom take more than 3 weeks of vacation per year. Financial considerations also contribute to this decision, as revealed in the survey.
 

Vacation Lowers Risk

Further analysis showed that doctors who took more than 3 weeks of vacation per year, which is not common, had a lower risk of developing burnout. Having coverage for vacation was also associated with reduced burnout risk and increased professional fulfillment.

However, these benefits applied only when physicians truly took a break during their vacation. Respondents who spent 30 minutes or more per day on patient-related work had a higher burnout risk. The risk was 1.58 times greater for 30-60 minutes, 1.97 times greater for 60-90 minutes, and 1.92 times greater for more than 90 minutes.
 

System-Level Interventions

The vacation behavior observed in this study likely exacerbates the effects of chronic workplace overload that are associated with long working hours, thus increasing the risk for burnout, according to the researchers.

“System-level measures must be implemented to ensure physicians take an appropriate number of vacation days,” wrote the researchers. “This includes having coverage available to handle clinical activities and administrative tasks, such as managing the EHR inbox. This could potentially reduce the burnout rate among physicians.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

TOPLINE:

Mental health comorbidities are prevalent among youth with overweight or obesity, with the strongest risk factors being male sex, older age, and extreme obesity.

METHODOLOGY:

• Researchers compared clinical characteristics and outcomes among children, adolescents, and young adults with overweight or obesity with or without a comorbid mental disorder who participated in a lifestyle intervention program.
• Overall, data from 114,248 individuals (age, 6-30 years; 53% females) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry were evaluated.
• Individuals were excluded if they had bariatric surgery or used weight-modifying drugs (metformin, orlistat, or glucagon-like peptide-1 analogues).
• Body mass index (BMI) was calculated as a standard deviation score (SDS) from a German youth population reference and was used to define overweight (90th to < 97th percentile), obesity (97th percentile), and severe obesity (≥ 99.5th percentile), which at age 18 correspond to adult cutoffs for overweight and obesity (25 kg/m² and 30 kg/m², respectively).
• Regression analysis identified the factors associated with mental disorders in those with overweight or obesity.

TAKEAWAY:

• A comorbid mental disorder was reported in 3969 individuals, with attention-deficit disorder (ADHD, 42.5%), anxiety (31.3%), depression (24.3%), and eating disorders (12.9%) being the most common.
• The factors most strongly associated with mental health comorbidity were male sex (odds ratio [OR], 1.39; 95% CI, 1.27-1.52), older age (OR, 1.42; 95% CI, 1.25-1.62), and severe obesity (OR, 1.45; 95% CI, 1.30-1.63).
• Mean BMI-SDS was higher in individuals with depression and eating disorders and lower in individuals with ADHD (both P < .001) than in those without mental disorders.
• Individuals with and without mental disorders benefited from similar BMI changes from lifestyle intervention programs.

IN PRACTICE:

The authors wrote, “Healthcare professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders, and regular mental health screening should be considered.”

SOURCE:

This study, led by Angela Galler from the Charité – Universitätsmedizin Berlin, Germany, was published online on January 9, 2024, in the International Journal of Obesity.

LIMITATIONS:

The study’s findings are based on data from a group of children, adolescents, and young adults with overweight or obesity treated in specialized obesity centers and may not be generalizable to all youth with obesity. Moreover, the study could not establish any conclusions regarding the cause or effect between obesity and mental disorders. Individuals were not tested psychologically for mental disorders and might have been underreported.

DISCLOSURES:

The manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which was funded by the Innovative Medicines Initiative 2 Joint Undertaking. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Mental health comorbidities are prevalent among youth with overweight or obesity, with the strongest risk factors being male sex, older age, and extreme obesity.

METHODOLOGY:

• Researchers compared clinical characteristics and outcomes among children, adolescents, and young adults with overweight or obesity with or without a comorbid mental disorder who participated in a lifestyle intervention program.
• Overall, data from 114,248 individuals (age, 6-30 years; 53% females) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry were evaluated.
• Individuals were excluded if they had bariatric surgery or used weight-modifying drugs (metformin, orlistat, or glucagon-like peptide-1 analogues).
• Body mass index (BMI) was calculated as a standard deviation score (SDS) from a German youth population reference and was used to define overweight (90th to < 97th percentile), obesity (97th percentile), and severe obesity (≥ 99.5th percentile), which at age 18 correspond to adult cutoffs for overweight and obesity (25 kg/m² and 30 kg/m², respectively).
• Regression analysis identified the factors associated with mental disorders in those with overweight or obesity.

TAKEAWAY:

• A comorbid mental disorder was reported in 3969 individuals, with attention-deficit disorder (ADHD, 42.5%), anxiety (31.3%), depression (24.3%), and eating disorders (12.9%) being the most common.
• The factors most strongly associated with mental health comorbidity were male sex (odds ratio [OR], 1.39; 95% CI, 1.27-1.52), older age (OR, 1.42; 95% CI, 1.25-1.62), and severe obesity (OR, 1.45; 95% CI, 1.30-1.63).
• Mean BMI-SDS was higher in individuals with depression and eating disorders and lower in individuals with ADHD (both P < .001) than in those without mental disorders.
• Individuals with and without mental disorders benefited from similar BMI changes from lifestyle intervention programs.

IN PRACTICE:

The authors wrote, “Healthcare professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders, and regular mental health screening should be considered.”

SOURCE:

This study, led by Angela Galler from the Charité – Universitätsmedizin Berlin, Germany, was published online on January 9, 2024, in the International Journal of Obesity.

LIMITATIONS:

The study’s findings are based on data from a group of children, adolescents, and young adults with overweight or obesity treated in specialized obesity centers and may not be generalizable to all youth with obesity. Moreover, the study could not establish any conclusions regarding the cause or effect between obesity and mental disorders. Individuals were not tested psychologically for mental disorders and might have been underreported.

DISCLOSURES:

The manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which was funded by the Innovative Medicines Initiative 2 Joint Undertaking. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Mental health comorbidities are prevalent among youth with overweight or obesity, with the strongest risk factors being male sex, older age, and extreme obesity.

METHODOLOGY:

• Researchers compared clinical characteristics and outcomes among children, adolescents, and young adults with overweight or obesity with or without a comorbid mental disorder who participated in a lifestyle intervention program.
• Overall, data from 114,248 individuals (age, 6-30 years; 53% females) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry were evaluated.
• Individuals were excluded if they had bariatric surgery or used weight-modifying drugs (metformin, orlistat, or glucagon-like peptide-1 analogues).
• Body mass index (BMI) was calculated as a standard deviation score (SDS) from a German youth population reference and was used to define overweight (90th to < 97th percentile), obesity (97th percentile), and severe obesity (≥ 99.5th percentile), which at age 18 correspond to adult cutoffs for overweight and obesity (25 kg/m² and 30 kg/m², respectively).
• Regression analysis identified the factors associated with mental disorders in those with overweight or obesity.

TAKEAWAY:

• A comorbid mental disorder was reported in 3969 individuals, with attention-deficit disorder (ADHD, 42.5%), anxiety (31.3%), depression (24.3%), and eating disorders (12.9%) being the most common.
• The factors most strongly associated with mental health comorbidity were male sex (odds ratio [OR], 1.39; 95% CI, 1.27-1.52), older age (OR, 1.42; 95% CI, 1.25-1.62), and severe obesity (OR, 1.45; 95% CI, 1.30-1.63).
• Mean BMI-SDS was higher in individuals with depression and eating disorders and lower in individuals with ADHD (both P < .001) than in those without mental disorders.
• Individuals with and without mental disorders benefited from similar BMI changes from lifestyle intervention programs.

IN PRACTICE:

The authors wrote, “Healthcare professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders, and regular mental health screening should be considered.”

SOURCE:

This study, led by Angela Galler from the Charité – Universitätsmedizin Berlin, Germany, was published online on January 9, 2024, in the International Journal of Obesity.

LIMITATIONS:

The study’s findings are based on data from a group of children, adolescents, and young adults with overweight or obesity treated in specialized obesity centers and may not be generalizable to all youth with obesity. Moreover, the study could not establish any conclusions regarding the cause or effect between obesity and mental disorders. Individuals were not tested psychologically for mental disorders and might have been underreported.

DISCLOSURES:

The manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which was funded by the Innovative Medicines Initiative 2 Joint Undertaking. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Bone health begins in childhood, particularly during the rapid bone accrual phase of puberty, which is essential for attaining optimal peak bone mass. Peak bone mass is achieved in early adult life and affects both immediate and future fracture risk. Genetic, nutritional, exercise-related, and hormonal factors, and certain diseases and medications, have deleterious effects on bone health.

In addition, emerging data suggest that certain manmade chemicals known as per- and polyfluoroalkyl substances (PFAS) may affect bone accrual during this important period and potentially increase the risk for osteoporosis in adulthood. Osteoporosis refers to increased fracture risk because of low bone density and affects a large proportion of postmenopausal women and older men.

New evidence comes from a recent study conducted by investigators from the Keck School of Medicine, who examined the impact of exposure to PFAS on skeletal outcomes in youth. Of note, participants were primarily Hispanic; this population has a higher risk for osteoporosis in adulthood. PFAS are manmade chemicals with water- and grease-resistant properties. They are used in a variety of products, such as nonstick cookware, food packaging, water-repellent clothing, stain-resistant fabrics, carpets, and in certain industrial processes. They are pervasive in the environment, in wildlife, and in humans.

Use and production of certain PFAS, such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA),  have decreased over the past two decades, with a significant reduction in blood concentrations of these chemicals. However, they can be resistant to degradation and have very long half-lives. As a consequence, these «forever chemicals» continue to linger in the environment. Also, the risk for exposure to other PFAS persists, and almost every individual has detectable levels of PFAS in blood.

Scientists are still learning about the impact of environmental chemicals on bone health. In contrast, other factors that may jeopardize pubertal bone accrual and peak bone mass acquisition have been studied extensively, with guidelines for management of the consequent poor skeletal health.

For PFAS, studies have reported deleterious effects on various body systems, such as the liver, immune system, thyroid, and the developing brain. The limited data related to bone suggest negative associations between certain, but not all, PFAS and bone density — ie, the higher the exposure, the worse the impact on bone health.

PFAS may affect health through alterations in the endocrine system. They have been associated with lower levels of testosterone and downregulation of its receptor (and testosterone is known to modulate bone formation and bone loss). On the other hand, some PFAS are estrogenic, which should be beneficial to bone. A direct impact of PFAS on pathways regulating activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) has also been postulated, with conflicting results.

Previous research on PFAS and human bone health has found mixed results. In adolescents, Xiong and colleagues  reported negative associations of PFOS, PFOA, and perfluorononanoic acid (PFNA), but not perfluorohexane sulfonic acid (PFHxS), levels with bone density at various sites, mostly in females. Carwile and associates  reported similar negative associations of blood concentrations of PFOA and PFOS and urinary concentrations of phthalates with bone density in adolescents, but only in males. Lin and coworkers also reported negative associations of PFOA and bone density in adult premenopausal women, but found no associations of PFOA and PFOS concentrations with self-reported fractures, suggesting questionable biological significance of these findings. These were all cross-sectional studies and did not report on the impact of these chemicals on longitudinal bone accrual.

In the recent study, Beglarian and colleagues examined the impact of PFAS on longitudinal changes in bone density in adolescents, drawn from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR) cohort and young adults from the Southern California Children’s Health Study (CHS) cohort. They found that in adolescents, higher baseline concentrations of PFOS predicted lower bone accrual over time. In young adults, there was a similar negative association of PFOS concentrations and bone density at baseline, but not with longitudinal bone accrual. In this study, other PFAS were not associated with bone outcomes.

Overall, research appears to suggest that PFOA, PFOS, and PFNA may have deleterious effects on bone density and bone accrual over time. However, data are not consistent across studies and across sexes, and more research is necessary to conclusively define the impact of these chemicals on skeletal health, particularly during the critical pubertal years of maximal bone accrual. In the meantime, continued efforts are necessary to reduce to concentrations of these PFAS in the environment.

Dr. Misra disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Bone health begins in childhood, particularly during the rapid bone accrual phase of puberty, which is essential for attaining optimal peak bone mass. Peak bone mass is achieved in early adult life and affects both immediate and future fracture risk. Genetic, nutritional, exercise-related, and hormonal factors, and certain diseases and medications, have deleterious effects on bone health.

In addition, emerging data suggest that certain manmade chemicals known as per- and polyfluoroalkyl substances (PFAS) may affect bone accrual during this important period and potentially increase the risk for osteoporosis in adulthood. Osteoporosis refers to increased fracture risk because of low bone density and affects a large proportion of postmenopausal women and older men.

New evidence comes from a recent study conducted by investigators from the Keck School of Medicine, who examined the impact of exposure to PFAS on skeletal outcomes in youth. Of note, participants were primarily Hispanic; this population has a higher risk for osteoporosis in adulthood. PFAS are manmade chemicals with water- and grease-resistant properties. They are used in a variety of products, such as nonstick cookware, food packaging, water-repellent clothing, stain-resistant fabrics, carpets, and in certain industrial processes. They are pervasive in the environment, in wildlife, and in humans.

Use and production of certain PFAS, such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA),  have decreased over the past two decades, with a significant reduction in blood concentrations of these chemicals. However, they can be resistant to degradation and have very long half-lives. As a consequence, these «forever chemicals» continue to linger in the environment. Also, the risk for exposure to other PFAS persists, and almost every individual has detectable levels of PFAS in blood.

Scientists are still learning about the impact of environmental chemicals on bone health. In contrast, other factors that may jeopardize pubertal bone accrual and peak bone mass acquisition have been studied extensively, with guidelines for management of the consequent poor skeletal health.

For PFAS, studies have reported deleterious effects on various body systems, such as the liver, immune system, thyroid, and the developing brain. The limited data related to bone suggest negative associations between certain, but not all, PFAS and bone density — ie, the higher the exposure, the worse the impact on bone health.

PFAS may affect health through alterations in the endocrine system. They have been associated with lower levels of testosterone and downregulation of its receptor (and testosterone is known to modulate bone formation and bone loss). On the other hand, some PFAS are estrogenic, which should be beneficial to bone. A direct impact of PFAS on pathways regulating activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) has also been postulated, with conflicting results.

Previous research on PFAS and human bone health has found mixed results. In adolescents, Xiong and colleagues  reported negative associations of PFOS, PFOA, and perfluorononanoic acid (PFNA), but not perfluorohexane sulfonic acid (PFHxS), levels with bone density at various sites, mostly in females. Carwile and associates  reported similar negative associations of blood concentrations of PFOA and PFOS and urinary concentrations of phthalates with bone density in adolescents, but only in males. Lin and coworkers also reported negative associations of PFOA and bone density in adult premenopausal women, but found no associations of PFOA and PFOS concentrations with self-reported fractures, suggesting questionable biological significance of these findings. These were all cross-sectional studies and did not report on the impact of these chemicals on longitudinal bone accrual.

In the recent study, Beglarian and colleagues examined the impact of PFAS on longitudinal changes in bone density in adolescents, drawn from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR) cohort and young adults from the Southern California Children’s Health Study (CHS) cohort. They found that in adolescents, higher baseline concentrations of PFOS predicted lower bone accrual over time. In young adults, there was a similar negative association of PFOS concentrations and bone density at baseline, but not with longitudinal bone accrual. In this study, other PFAS were not associated with bone outcomes.

Overall, research appears to suggest that PFOA, PFOS, and PFNA may have deleterious effects on bone density and bone accrual over time. However, data are not consistent across studies and across sexes, and more research is necessary to conclusively define the impact of these chemicals on skeletal health, particularly during the critical pubertal years of maximal bone accrual. In the meantime, continued efforts are necessary to reduce to concentrations of these PFAS in the environment.

Dr. Misra disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Bone health begins in childhood, particularly during the rapid bone accrual phase of puberty, which is essential for attaining optimal peak bone mass. Peak bone mass is achieved in early adult life and affects both immediate and future fracture risk. Genetic, nutritional, exercise-related, and hormonal factors, and certain diseases and medications, have deleterious effects on bone health.

In addition, emerging data suggest that certain manmade chemicals known as per- and polyfluoroalkyl substances (PFAS) may affect bone accrual during this important period and potentially increase the risk for osteoporosis in adulthood. Osteoporosis refers to increased fracture risk because of low bone density and affects a large proportion of postmenopausal women and older men.

New evidence comes from a recent study conducted by investigators from the Keck School of Medicine, who examined the impact of exposure to PFAS on skeletal outcomes in youth. Of note, participants were primarily Hispanic; this population has a higher risk for osteoporosis in adulthood. PFAS are manmade chemicals with water- and grease-resistant properties. They are used in a variety of products, such as nonstick cookware, food packaging, water-repellent clothing, stain-resistant fabrics, carpets, and in certain industrial processes. They are pervasive in the environment, in wildlife, and in humans.

Use and production of certain PFAS, such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA),  have decreased over the past two decades, with a significant reduction in blood concentrations of these chemicals. However, they can be resistant to degradation and have very long half-lives. As a consequence, these «forever chemicals» continue to linger in the environment. Also, the risk for exposure to other PFAS persists, and almost every individual has detectable levels of PFAS in blood.

Scientists are still learning about the impact of environmental chemicals on bone health. In contrast, other factors that may jeopardize pubertal bone accrual and peak bone mass acquisition have been studied extensively, with guidelines for management of the consequent poor skeletal health.

For PFAS, studies have reported deleterious effects on various body systems, such as the liver, immune system, thyroid, and the developing brain. The limited data related to bone suggest negative associations between certain, but not all, PFAS and bone density — ie, the higher the exposure, the worse the impact on bone health.

PFAS may affect health through alterations in the endocrine system. They have been associated with lower levels of testosterone and downregulation of its receptor (and testosterone is known to modulate bone formation and bone loss). On the other hand, some PFAS are estrogenic, which should be beneficial to bone. A direct impact of PFAS on pathways regulating activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) has also been postulated, with conflicting results.

Previous research on PFAS and human bone health has found mixed results. In adolescents, Xiong and colleagues  reported negative associations of PFOS, PFOA, and perfluorononanoic acid (PFNA), but not perfluorohexane sulfonic acid (PFHxS), levels with bone density at various sites, mostly in females. Carwile and associates  reported similar negative associations of blood concentrations of PFOA and PFOS and urinary concentrations of phthalates with bone density in adolescents, but only in males. Lin and coworkers also reported negative associations of PFOA and bone density in adult premenopausal women, but found no associations of PFOA and PFOS concentrations with self-reported fractures, suggesting questionable biological significance of these findings. These were all cross-sectional studies and did not report on the impact of these chemicals on longitudinal bone accrual.

In the recent study, Beglarian and colleagues examined the impact of PFAS on longitudinal changes in bone density in adolescents, drawn from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR) cohort and young adults from the Southern California Children’s Health Study (CHS) cohort. They found that in adolescents, higher baseline concentrations of PFOS predicted lower bone accrual over time. In young adults, there was a similar negative association of PFOS concentrations and bone density at baseline, but not with longitudinal bone accrual. In this study, other PFAS were not associated with bone outcomes.

Overall, research appears to suggest that PFOA, PFOS, and PFNA may have deleterious effects on bone density and bone accrual over time. However, data are not consistent across studies and across sexes, and more research is necessary to conclusively define the impact of these chemicals on skeletal health, particularly during the critical pubertal years of maximal bone accrual. In the meantime, continued efforts are necessary to reduce to concentrations of these PFAS in the environment.

Dr. Misra disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A daily low dose of colchicine significantly reduces ischemic cardiovascular events in patients with type 2 diabetes (T2D) and a recent myocardial infarction (MI). 

METHODOLOGY:

• After an MI, patients with vs without T2D have a higher risk for another cardiovascular event.
• The Colchicine Cardiovascular Outcomes Trial (COLCOT), a randomized, double-blinded trial, found a lower risk for ischemic cardiovascular events with 0.5 mg colchicine taken daily vs placebo, initiated within 30 days of an MI.
• Researchers conducted a prespecified subgroup analysis of 959 adult patients with T2D (mean age, 62.4 years; 22.2% women) in COLCOT (462 patients in colchicine and 497 patients in placebo groups).
• The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization within a median 23 months.
• The patients were taking a variety of appropriate medications, including aspirin and another antiplatelet agent and a statin (98%-99%) and metformin (75%-76%).

TAKEAWAY:

• The risk for the primary endpoint was reduced by 35% in patients with T2D who received colchicine than in those who received placebo (hazard ratio, 0.65; P = .03).
• The primary endpoint event rate per 100 patient-months was significantly lower in the colchicine group than in the placebo group (rate ratio, 0.53; P = .01).
• The frequencies of adverse events were similar in both the treatment and placebo groups (14.6% and 12.8%, respectively; P = .41), with gastrointestinal adverse events being the most common.
• In COLCOT, patients with T2D had a 1.86-fold higher risk for a primary endpoint cardiovascular event, but there was no significant difference in the primary endpoint between those with and without T2D on colchicine.

IN PRACTICE:

“Patients with both T2D and a recent MI derive a large benefit from inflammation-reducing therapy with colchicine,” the authors noted.

SOURCE:

This study, led by François Roubille, University Hospital of Montpellier, France, was published online on January 5, 2024, in Diabetes Care. 

LIMITATIONS:

Patients were not stratified at inclusion for the presence of diabetes. Also, the study did not evaluate the role of glycated hemoglobin and low-density lipoprotein cholesterol, as well as the effects of different glucose-lowering medications or possible hypoglycemic episodes.

DISCLOSURES:

The COLCOT study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Coauthors Jean-Claude Tardif and Wolfgang Koenig declared receiving research grants, honoraria, advisory board fees, and lecture fees from pharmaceutical companies, as well as having other ties with various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A daily low dose of colchicine significantly reduces ischemic cardiovascular events in patients with type 2 diabetes (T2D) and a recent myocardial infarction (MI). 

METHODOLOGY:

• After an MI, patients with vs without T2D have a higher risk for another cardiovascular event.
• The Colchicine Cardiovascular Outcomes Trial (COLCOT), a randomized, double-blinded trial, found a lower risk for ischemic cardiovascular events with 0.5 mg colchicine taken daily vs placebo, initiated within 30 days of an MI.
• Researchers conducted a prespecified subgroup analysis of 959 adult patients with T2D (mean age, 62.4 years; 22.2% women) in COLCOT (462 patients in colchicine and 497 patients in placebo groups).
• The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization within a median 23 months.
• The patients were taking a variety of appropriate medications, including aspirin and another antiplatelet agent and a statin (98%-99%) and metformin (75%-76%).

TAKEAWAY:

• The risk for the primary endpoint was reduced by 35% in patients with T2D who received colchicine than in those who received placebo (hazard ratio, 0.65; P = .03).
• The primary endpoint event rate per 100 patient-months was significantly lower in the colchicine group than in the placebo group (rate ratio, 0.53; P = .01).
• The frequencies of adverse events were similar in both the treatment and placebo groups (14.6% and 12.8%, respectively; P = .41), with gastrointestinal adverse events being the most common.
• In COLCOT, patients with T2D had a 1.86-fold higher risk for a primary endpoint cardiovascular event, but there was no significant difference in the primary endpoint between those with and without T2D on colchicine.

IN PRACTICE:

“Patients with both T2D and a recent MI derive a large benefit from inflammation-reducing therapy with colchicine,” the authors noted.

SOURCE:

This study, led by François Roubille, University Hospital of Montpellier, France, was published online on January 5, 2024, in Diabetes Care. 

LIMITATIONS:

Patients were not stratified at inclusion for the presence of diabetes. Also, the study did not evaluate the role of glycated hemoglobin and low-density lipoprotein cholesterol, as well as the effects of different glucose-lowering medications or possible hypoglycemic episodes.

DISCLOSURES:

The COLCOT study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Coauthors Jean-Claude Tardif and Wolfgang Koenig declared receiving research grants, honoraria, advisory board fees, and lecture fees from pharmaceutical companies, as well as having other ties with various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A daily low dose of colchicine significantly reduces ischemic cardiovascular events in patients with type 2 diabetes (T2D) and a recent myocardial infarction (MI). 

METHODOLOGY:

• After an MI, patients with vs without T2D have a higher risk for another cardiovascular event.
• The Colchicine Cardiovascular Outcomes Trial (COLCOT), a randomized, double-blinded trial, found a lower risk for ischemic cardiovascular events with 0.5 mg colchicine taken daily vs placebo, initiated within 30 days of an MI.
• Researchers conducted a prespecified subgroup analysis of 959 adult patients with T2D (mean age, 62.4 years; 22.2% women) in COLCOT (462 patients in colchicine and 497 patients in placebo groups).
• The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization within a median 23 months.
• The patients were taking a variety of appropriate medications, including aspirin and another antiplatelet agent and a statin (98%-99%) and metformin (75%-76%).

TAKEAWAY:

• The risk for the primary endpoint was reduced by 35% in patients with T2D who received colchicine than in those who received placebo (hazard ratio, 0.65; P = .03).
• The primary endpoint event rate per 100 patient-months was significantly lower in the colchicine group than in the placebo group (rate ratio, 0.53; P = .01).
• The frequencies of adverse events were similar in both the treatment and placebo groups (14.6% and 12.8%, respectively; P = .41), with gastrointestinal adverse events being the most common.
• In COLCOT, patients with T2D had a 1.86-fold higher risk for a primary endpoint cardiovascular event, but there was no significant difference in the primary endpoint between those with and without T2D on colchicine.

IN PRACTICE:

“Patients with both T2D and a recent MI derive a large benefit from inflammation-reducing therapy with colchicine,” the authors noted.

SOURCE:

This study, led by François Roubille, University Hospital of Montpellier, France, was published online on January 5, 2024, in Diabetes Care. 

LIMITATIONS:

Patients were not stratified at inclusion for the presence of diabetes. Also, the study did not evaluate the role of glycated hemoglobin and low-density lipoprotein cholesterol, as well as the effects of different glucose-lowering medications or possible hypoglycemic episodes.

DISCLOSURES:

The COLCOT study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Coauthors Jean-Claude Tardif and Wolfgang Koenig declared receiving research grants, honoraria, advisory board fees, and lecture fees from pharmaceutical companies, as well as having other ties with various sources.
 

A version of this article appeared on Medscape.com.

A recently published prospective study in JAMA Network Open identified a significant association between children’s bone health and their proximity to green areas.

The literature emphasized the benefits of childhood exposure to green spaces for neurocognitive, social, behavioral, and mental development, as well as well-being. In addition, such exposure is linked to lower body mass index, increased physical activity, and reduced risks for overweight, obesity, and hypertension. However, specific data on bone mineral density implications are limited.

To address this gap, Hanne Sleurs, PhD, a researcher at the Universiteit Hasselt in Belgium, and colleagues followed the bone health of 327 participants from birth to 4-6 years and examined correlations with individuals’ exposure to green areas. Data collection occurred from October 2014 to July 2021.

Green spaces were categorized as high (vegetation height > 3 m), low (vegetation height ≤ 3 m), and mixed (combination of both). The distances of green spaces from participants’ residences ranged from a radius of 100 m to 3 km. Radial bone mineral density assessment was conducted using quantitative ultrasound during follow-up consultations.

The scientists found that participants frequently exposed to high and mixed vegetation areas within a 500-m radius of their homes had significantly higher bone mineral density than those at other distances or those frequenting spaces with different vegetation. In addition, access to larger green spaces with mixed and high vegetation within a 1-km radius was significantly associated with a lower likelihood of low bone density in children.

“These findings illustrate the positive impact on bone health of early childhood exposure to green areas near their homes during critical growth and development periods, with long-term implications,” wrote the researchers.

The results aligned with those of a prior study in which authors noted factors contributing to families’ frequent park visits, including shorter distances, safety, and park organization, as well as the natural diversity and activities offered.

One hypothesis explaining improved bone density in children visiting green areas was increased physical activity practiced in these locations. The mechanical load from exercise can activate signaling pathways favoring bone development. Literature also gathered data on the influence of green areas on young populations engaging in physical activities, showing positive outcomes.

According to the study authors, the findings are crucial for public health because they emphasize the need for urban investments in accessible green spaces as a strategy for fracture and osteoporosis prevention. In the long term, such initiatives translate to reduced public health expenses, along with physical and emotional gains in communities adopting environmental strategies, they concluded.

This article was translated from the Medscape Portuguese edition. A version of this article appeared on Medscape.com.

A recently published prospective study in JAMA Network Open identified a significant association between children’s bone health and their proximity to green areas.

The literature emphasized the benefits of childhood exposure to green spaces for neurocognitive, social, behavioral, and mental development, as well as well-being. In addition, such exposure is linked to lower body mass index, increased physical activity, and reduced risks for overweight, obesity, and hypertension. However, specific data on bone mineral density implications are limited.

To address this gap, Hanne Sleurs, PhD, a researcher at the Universiteit Hasselt in Belgium, and colleagues followed the bone health of 327 participants from birth to 4-6 years and examined correlations with individuals’ exposure to green areas. Data collection occurred from October 2014 to July 2021.

Green spaces were categorized as high (vegetation height > 3 m), low (vegetation height ≤ 3 m), and mixed (combination of both). The distances of green spaces from participants’ residences ranged from a radius of 100 m to 3 km. Radial bone mineral density assessment was conducted using quantitative ultrasound during follow-up consultations.

The scientists found that participants frequently exposed to high and mixed vegetation areas within a 500-m radius of their homes had significantly higher bone mineral density than those at other distances or those frequenting spaces with different vegetation. In addition, access to larger green spaces with mixed and high vegetation within a 1-km radius was significantly associated with a lower likelihood of low bone density in children.

“These findings illustrate the positive impact on bone health of early childhood exposure to green areas near their homes during critical growth and development periods, with long-term implications,” wrote the researchers.

The results aligned with those of a prior study in which authors noted factors contributing to families’ frequent park visits, including shorter distances, safety, and park organization, as well as the natural diversity and activities offered.

One hypothesis explaining improved bone density in children visiting green areas was increased physical activity practiced in these locations. The mechanical load from exercise can activate signaling pathways favoring bone development. Literature also gathered data on the influence of green areas on young populations engaging in physical activities, showing positive outcomes.

According to the study authors, the findings are crucial for public health because they emphasize the need for urban investments in accessible green spaces as a strategy for fracture and osteoporosis prevention. In the long term, such initiatives translate to reduced public health expenses, along with physical and emotional gains in communities adopting environmental strategies, they concluded.

This article was translated from the Medscape Portuguese edition. A version of this article appeared on Medscape.com.

A recently published prospective study in JAMA Network Open identified a significant association between children’s bone health and their proximity to green areas.

The literature emphasized the benefits of childhood exposure to green spaces for neurocognitive, social, behavioral, and mental development, as well as well-being. In addition, such exposure is linked to lower body mass index, increased physical activity, and reduced risks for overweight, obesity, and hypertension. However, specific data on bone mineral density implications are limited.

To address this gap, Hanne Sleurs, PhD, a researcher at the Universiteit Hasselt in Belgium, and colleagues followed the bone health of 327 participants from birth to 4-6 years and examined correlations with individuals’ exposure to green areas. Data collection occurred from October 2014 to July 2021.

Green spaces were categorized as high (vegetation height > 3 m), low (vegetation height ≤ 3 m), and mixed (combination of both). The distances of green spaces from participants’ residences ranged from a radius of 100 m to 3 km. Radial bone mineral density assessment was conducted using quantitative ultrasound during follow-up consultations.

The scientists found that participants frequently exposed to high and mixed vegetation areas within a 500-m radius of their homes had significantly higher bone mineral density than those at other distances or those frequenting spaces with different vegetation. In addition, access to larger green spaces with mixed and high vegetation within a 1-km radius was significantly associated with a lower likelihood of low bone density in children.

“These findings illustrate the positive impact on bone health of early childhood exposure to green areas near their homes during critical growth and development periods, with long-term implications,” wrote the researchers.

The results aligned with those of a prior study in which authors noted factors contributing to families’ frequent park visits, including shorter distances, safety, and park organization, as well as the natural diversity and activities offered.

One hypothesis explaining improved bone density in children visiting green areas was increased physical activity practiced in these locations. The mechanical load from exercise can activate signaling pathways favoring bone development. Literature also gathered data on the influence of green areas on young populations engaging in physical activities, showing positive outcomes.

According to the study authors, the findings are crucial for public health because they emphasize the need for urban investments in accessible green spaces as a strategy for fracture and osteoporosis prevention. In the long term, such initiatives translate to reduced public health expenses, along with physical and emotional gains in communities adopting environmental strategies, they concluded.

This article was translated from the Medscape Portuguese edition. A version of this article appeared on Medscape.com.

TOPLINE:

In patients with chronic kidney disease (CKD) and type 2 diabetes, baseline insulin resistance was associated with increased cardiovascular (CV) but not kidney risk and did not affect the efficacy of finerenone. 

METHODOLOGY:

• Insulin resistance is implicated in CV disease in patients with CKD, but its role in CKD progression is less clear.
• This post hoc analysis of FIDELITY, a pooled analysis of the  and  trials, randomly assigned patients with type 2 diabetes and CKD (who received optimized renin-angiotensin system blockade) to receive finerenone (10 mg or 20 mg) once daily or placebo and followed them for a median of 3 years.
• An estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated for 12,964 patients (median age, 65 years), using waist circumference, hypertension status, and glycated hemoglobin.
• Outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (time to renal failure, a sustained decrease ≥ 57% in the initial estimated glomerular filtration rate, or renal death).

TAKEAWAY:

• The median eGDR was 4.1 mg/kg/min. The 50% of patients with a lower eGDR were considered insulin resistant, whereas the remaining half with a higher eGDR were considered insulin sensitive.
• The incidence rate of CV outcomes was higher among patients with insulin resistance in both the finerenone group (incidence rate per 100 patient-years, 5.18 vs 3.47 among insulin-sensitive patients) and the placebo group (6.34 vs 3.76), but eGDR showed no association with kidney outcomes.
• The efficacy of finerenone vs placebo on CV (Wald test P = .063) and kidney outcomes (Wald test P = .51) did not change significantly across the range of baseline eGDR values.
• The incidences of treatment-emergent adverse events and severe adverse events with finerenone were similar between the insulin-resistant and insulin-sensitive subgroups.

IN PRACTICE:

“The efficacy and safety of finerenone were not modified by baseline insulin resistance. A higher risk of CV — but not kidney outcomes was observed in patients with CKD and T2D with greater insulin resistance,” the authors wrote.

SOURCE:

This study was led by Thomas Ebert of the Medical Department III — Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany, and published online in Diabetes Care.

LIMITATIONS:

This study was not adequately powered to evaluate the statistical significance of the association of eGDR with CV and kidney outcomes and was hypothesis-generating. Further studies are needed to examine whether the effects of insulin resistance differ between individuals with diabetes vs those with advanced CKD with or without diabetes.

DISCLOSURES:

The FIDELIO-DKD and FIGARO-DKD trials were conducted and sponsored by Bayer AG. Three authors declared being full-time employees of Bayer. Several authors declared receiving personal fees, consulting fees, grants, or research support from; holding patents with; or having ownership interests in various pharmaceutical companies, including Bayer.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with chronic kidney disease (CKD) and type 2 diabetes, baseline insulin resistance was associated with increased cardiovascular (CV) but not kidney risk and did not affect the efficacy of finerenone. 

METHODOLOGY:

• Insulin resistance is implicated in CV disease in patients with CKD, but its role in CKD progression is less clear.
• This post hoc analysis of FIDELITY, a pooled analysis of the  and  trials, randomly assigned patients with type 2 diabetes and CKD (who received optimized renin-angiotensin system blockade) to receive finerenone (10 mg or 20 mg) once daily or placebo and followed them for a median of 3 years.
• An estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated for 12,964 patients (median age, 65 years), using waist circumference, hypertension status, and glycated hemoglobin.
• Outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (time to renal failure, a sustained decrease ≥ 57% in the initial estimated glomerular filtration rate, or renal death).

TAKEAWAY:

• The median eGDR was 4.1 mg/kg/min. The 50% of patients with a lower eGDR were considered insulin resistant, whereas the remaining half with a higher eGDR were considered insulin sensitive.
• The incidence rate of CV outcomes was higher among patients with insulin resistance in both the finerenone group (incidence rate per 100 patient-years, 5.18 vs 3.47 among insulin-sensitive patients) and the placebo group (6.34 vs 3.76), but eGDR showed no association with kidney outcomes.
• The efficacy of finerenone vs placebo on CV (Wald test P = .063) and kidney outcomes (Wald test P = .51) did not change significantly across the range of baseline eGDR values.
• The incidences of treatment-emergent adverse events and severe adverse events with finerenone were similar between the insulin-resistant and insulin-sensitive subgroups.

IN PRACTICE:

“The efficacy and safety of finerenone were not modified by baseline insulin resistance. A higher risk of CV — but not kidney outcomes was observed in patients with CKD and T2D with greater insulin resistance,” the authors wrote.

SOURCE:

This study was led by Thomas Ebert of the Medical Department III — Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany, and published online in Diabetes Care.

LIMITATIONS:

This study was not adequately powered to evaluate the statistical significance of the association of eGDR with CV and kidney outcomes and was hypothesis-generating. Further studies are needed to examine whether the effects of insulin resistance differ between individuals with diabetes vs those with advanced CKD with or without diabetes.

DISCLOSURES:

The FIDELIO-DKD and FIGARO-DKD trials were conducted and sponsored by Bayer AG. Three authors declared being full-time employees of Bayer. Several authors declared receiving personal fees, consulting fees, grants, or research support from; holding patents with; or having ownership interests in various pharmaceutical companies, including Bayer.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with chronic kidney disease (CKD) and type 2 diabetes, baseline insulin resistance was associated with increased cardiovascular (CV) but not kidney risk and did not affect the efficacy of finerenone. 

METHODOLOGY:

• Insulin resistance is implicated in CV disease in patients with CKD, but its role in CKD progression is less clear.
• This post hoc analysis of FIDELITY, a pooled analysis of the  and  trials, randomly assigned patients with type 2 diabetes and CKD (who received optimized renin-angiotensin system blockade) to receive finerenone (10 mg or 20 mg) once daily or placebo and followed them for a median of 3 years.
• An estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated for 12,964 patients (median age, 65 years), using waist circumference, hypertension status, and glycated hemoglobin.
• Outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (time to renal failure, a sustained decrease ≥ 57% in the initial estimated glomerular filtration rate, or renal death).

TAKEAWAY:

• The median eGDR was 4.1 mg/kg/min. The 50% of patients with a lower eGDR were considered insulin resistant, whereas the remaining half with a higher eGDR were considered insulin sensitive.
• The incidence rate of CV outcomes was higher among patients with insulin resistance in both the finerenone group (incidence rate per 100 patient-years, 5.18 vs 3.47 among insulin-sensitive patients) and the placebo group (6.34 vs 3.76), but eGDR showed no association with kidney outcomes.
• The efficacy of finerenone vs placebo on CV (Wald test P = .063) and kidney outcomes (Wald test P = .51) did not change significantly across the range of baseline eGDR values.
• The incidences of treatment-emergent adverse events and severe adverse events with finerenone were similar between the insulin-resistant and insulin-sensitive subgroups.

IN PRACTICE:

“The efficacy and safety of finerenone were not modified by baseline insulin resistance. A higher risk of CV — but not kidney outcomes was observed in patients with CKD and T2D with greater insulin resistance,” the authors wrote.

SOURCE:

This study was led by Thomas Ebert of the Medical Department III — Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany, and published online in Diabetes Care.

LIMITATIONS:

This study was not adequately powered to evaluate the statistical significance of the association of eGDR with CV and kidney outcomes and was hypothesis-generating. Further studies are needed to examine whether the effects of insulin resistance differ between individuals with diabetes vs those with advanced CKD with or without diabetes.

DISCLOSURES:

The FIDELIO-DKD and FIGARO-DKD trials were conducted and sponsored by Bayer AG. Three authors declared being full-time employees of Bayer. Several authors declared receiving personal fees, consulting fees, grants, or research support from; holding patents with; or having ownership interests in various pharmaceutical companies, including Bayer.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine. There has been an explosion of interest recently in bills that propose to extend medical assistance in dying to more Americans as states begin to contemplate legalization.

Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.

Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.

There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.

One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.

New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.

If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.

The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.

The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.

You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.

Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.

Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.

I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.

Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.

I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.

I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:

• Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
• Serves as a contributing author and adviser for: Medscape

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine. There has been an explosion of interest recently in bills that propose to extend medical assistance in dying to more Americans as states begin to contemplate legalization.

Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.

Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.

There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.

One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.

New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.

If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.

The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.

The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.

You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.

Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.

Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.

I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.

Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.

I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.

I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:

• Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
• Serves as a contributing author and adviser for: Medscape

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine. There has been an explosion of interest recently in bills that propose to extend medical assistance in dying to more Americans as states begin to contemplate legalization.

Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.

Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.

There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.

One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.

New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.

If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.

The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.

The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.

You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.

Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.

Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.

I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.

Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.

I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.

I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:

• Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
• Serves as a contributing author and adviser for: Medscape

A version of this article appeared on Medscape.com.

Recent reporting has shown that the number of physician-scientists — doctors who both practice medicine and perform scientific research — in the United States is dropping rapidly. That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.

So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?

Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.

The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.

Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.

Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.

Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.

The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.

Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.

Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent reporting has shown that the number of physician-scientists — doctors who both practice medicine and perform scientific research — in the United States is dropping rapidly. That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.

So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?

Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.

The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.

Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.

Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.

Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.

The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.

Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.

Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent reporting has shown that the number of physician-scientists — doctors who both practice medicine and perform scientific research — in the United States is dropping rapidly. That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.

So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?

Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.

The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.

Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.

Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.

Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.

The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.

Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.

Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.

Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.

#1: We’ll gain a better understanding of each long COVID phenotype

This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.

Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.

Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.

Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.

“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.

#2: Monoclonal antibodies may change the game

We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.

Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.

Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.

#3: Paxlovid could prove effective for long COVID

The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.

In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.

Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.

It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.

#4: Anti-inflammatories like metformin could prove useful

Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.

The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.

“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”

Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.

Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.

#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID

One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.

Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.

Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said last month in an interview with this news organization.

If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.

A version of this article appeared on Medscape.com.

With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.

Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.

#1: We’ll gain a better understanding of each long COVID phenotype

This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.

Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.

Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.

Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.

“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.

#2: Monoclonal antibodies may change the game

We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.

Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.

Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.

#3: Paxlovid could prove effective for long COVID

The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.

In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.

Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.

It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.

#4: Anti-inflammatories like metformin could prove useful

Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.

The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.

“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”

Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.

Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.

#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID

One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.

Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.

Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said last month in an interview with this news organization.

If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.

A version of this article appeared on Medscape.com.

With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.

Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.

#1: We’ll gain a better understanding of each long COVID phenotype

This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.

Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.

Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.

Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.

“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.

#2: Monoclonal antibodies may change the game

We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.

Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.

Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.

#3: Paxlovid could prove effective for long COVID

The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.

In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.

Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.

It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.

#4: Anti-inflammatories like metformin could prove useful

Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.

The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.

“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”

Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.

Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.

#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID

One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.

Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.

Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said last month in an interview with this news organization.

If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.

A version of this article appeared on Medscape.com.