The Food and Drug Administration (FDA) has approved the oral Janus kinase (JAK) inhibitor deuruxolitinib for the treatment of adults with severe alopecia areata.

The development, which was announced in a July 25, 2024, news release from the drug’s manufacturer Sun Pharma, is based on data from two pivotal randomized, double-blind, placebo-controlled phase 3 clinical trials: THRIVE-AA1 and THRIVE-AA2, which included 1220 adults with severe alopecia areata enrolled at sites in the United States, Canada, and Europe. Study participants had at least 50% scalp hair loss as measured by Severity of Alopecia Tool (SALT) for more than 6 months. Data were also collected from two open-label, long-term extension trials in which patients were eligible to enroll upon completion of the 24-week trials.

Deuruxolitinib, which comes in 8-mg tablets, is an oral selective inhibitor of JAK1 and JAK2 and is administered twice a day. According to the company press release, the average patient enrolled in the clinical trials had only 13% of their scalp hair coverage at baseline. At week 24, more than 30% of patients taking deuruxolitinib experiencing 80% or more scalp hair coverage (SALT score ≤ 20). Also, up to 25% of patients had almost all of their scalp hair back at 24 weeks (≥ 90% coverage).

In terms of safety, the data showed that 3.1% of patients who received deuruxolitinib 8 mg twice daily in the phase 2 dose-ranging study and phase 3 randomized placebo-controlled trials discontinued treatment owing to adverse reactions. The three most common adverse events in placebo-controlled trials were headache (12.4% vs 9.4% with placebo), acne (10% vs 4.3% with placebo), and nasopharyngitis (8.1% vs 6.7% with placebo). More than 100 people continued taking deuruxolitinib for more than 3 years.

Deuruxolitinib is the third treatment and third JAK inhibitor approved by the FDA for severe alopecia areata. Baricitinib (Olumiant) was approved in June 2022 for adults with alopecia areata, followed by ritlecitinib (Litfulo) approved in June 2023 for patients aged 12 years and older. 

In a statement from the National Alopecia Areata Foundation (NAAF), Nicole Friedland, NAAF’s president and CEO, said that “it is with tremendous excitement that we welcome the FDA’s approval of a third treatment for severe alopecia areata in as many years.”

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

The Food and Drug Administration (FDA) has approved the oral Janus kinase (JAK) inhibitor deuruxolitinib for the treatment of adults with severe alopecia areata.

The development, which was announced in a July 25, 2024, news release from the drug’s manufacturer Sun Pharma, is based on data from two pivotal randomized, double-blind, placebo-controlled phase 3 clinical trials: THRIVE-AA1 and THRIVE-AA2, which included 1220 adults with severe alopecia areata enrolled at sites in the United States, Canada, and Europe. Study participants had at least 50% scalp hair loss as measured by Severity of Alopecia Tool (SALT) for more than 6 months. Data were also collected from two open-label, long-term extension trials in which patients were eligible to enroll upon completion of the 24-week trials.

Deuruxolitinib, which comes in 8-mg tablets, is an oral selective inhibitor of JAK1 and JAK2 and is administered twice a day. According to the company press release, the average patient enrolled in the clinical trials had only 13% of their scalp hair coverage at baseline. At week 24, more than 30% of patients taking deuruxolitinib experiencing 80% or more scalp hair coverage (SALT score ≤ 20). Also, up to 25% of patients had almost all of their scalp hair back at 24 weeks (≥ 90% coverage).

In terms of safety, the data showed that 3.1% of patients who received deuruxolitinib 8 mg twice daily in the phase 2 dose-ranging study and phase 3 randomized placebo-controlled trials discontinued treatment owing to adverse reactions. The three most common adverse events in placebo-controlled trials were headache (12.4% vs 9.4% with placebo), acne (10% vs 4.3% with placebo), and nasopharyngitis (8.1% vs 6.7% with placebo). More than 100 people continued taking deuruxolitinib for more than 3 years.

Deuruxolitinib is the third treatment and third JAK inhibitor approved by the FDA for severe alopecia areata. Baricitinib (Olumiant) was approved in June 2022 for adults with alopecia areata, followed by ritlecitinib (Litfulo) approved in June 2023 for patients aged 12 years and older. 

In a statement from the National Alopecia Areata Foundation (NAAF), Nicole Friedland, NAAF’s president and CEO, said that “it is with tremendous excitement that we welcome the FDA’s approval of a third treatment for severe alopecia areata in as many years.”

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

The Food and Drug Administration (FDA) has approved the oral Janus kinase (JAK) inhibitor deuruxolitinib for the treatment of adults with severe alopecia areata.

The development, which was announced in a July 25, 2024, news release from the drug’s manufacturer Sun Pharma, is based on data from two pivotal randomized, double-blind, placebo-controlled phase 3 clinical trials: THRIVE-AA1 and THRIVE-AA2, which included 1220 adults with severe alopecia areata enrolled at sites in the United States, Canada, and Europe. Study participants had at least 50% scalp hair loss as measured by Severity of Alopecia Tool (SALT) for more than 6 months. Data were also collected from two open-label, long-term extension trials in which patients were eligible to enroll upon completion of the 24-week trials.

Deuruxolitinib, which comes in 8-mg tablets, is an oral selective inhibitor of JAK1 and JAK2 and is administered twice a day. According to the company press release, the average patient enrolled in the clinical trials had only 13% of their scalp hair coverage at baseline. At week 24, more than 30% of patients taking deuruxolitinib experiencing 80% or more scalp hair coverage (SALT score ≤ 20). Also, up to 25% of patients had almost all of their scalp hair back at 24 weeks (≥ 90% coverage).

In terms of safety, the data showed that 3.1% of patients who received deuruxolitinib 8 mg twice daily in the phase 2 dose-ranging study and phase 3 randomized placebo-controlled trials discontinued treatment owing to adverse reactions. The three most common adverse events in placebo-controlled trials were headache (12.4% vs 9.4% with placebo), acne (10% vs 4.3% with placebo), and nasopharyngitis (8.1% vs 6.7% with placebo). More than 100 people continued taking deuruxolitinib for more than 3 years.

Deuruxolitinib is the third treatment and third JAK inhibitor approved by the FDA for severe alopecia areata. Baricitinib (Olumiant) was approved in June 2022 for adults with alopecia areata, followed by ritlecitinib (Litfulo) approved in June 2023 for patients aged 12 years and older. 

In a statement from the National Alopecia Areata Foundation (NAAF), Nicole Friedland, NAAF’s president and CEO, said that “it is with tremendous excitement that we welcome the FDA’s approval of a third treatment for severe alopecia areata in as many years.”

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

Application of an investigative topical cannabidiol (CBD) cream to buttock skin demonstrated protective properties against ultraviolet A (UVA) radiation-induced DNA and mitochondrial DNA damage, results from a small prospective pilot study showed.

“This study hopefully reinvigorates interest in the utilization of whether it be plant-based, human-derived, or synthetic cannabinoids in the management of dermatologic disease,” one of the study investigators, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization. The study was published in the Journal of the American Academy of Dermatology.

George Washington University

For the prospective, single-center, pilot trial, which is believed to be the first of its kind, 19 volunteers aged 22-65 with Fitzpatrick skin types I-III applied either a nano-encapsulated CBD cream or a vehicle cream to blind spots on the skin of the buttocks twice daily for 14 days. Next, researchers applied a minimal erythema dose of UV radiation to the treated skin areas for 30 minutes. After 24 hours, they visually inspected the treated areas to clinically compare the erythema. They also performed five 4-mm punch biopsies from UVA- and non-UVA–exposed treatment sites on each buttock, as well as from an untreated control site that was at least 5 cm away from the treated left buttock.

At 24 hours, 21% of study participants showed less redness on CBD-treated skin compared with control-treated skin, while histology showed that CBD-treated skin demonstrated reduced UVA-induced epidermal hyperplasia compared with control-treated skin (a mean 11.3% change from baseline vs 28.7%, respectively; P = .01). In other findings, application of CBD cream reduced DNA damage and DNA mutations associated with UVA-induced skin aging/damage and ultimately skin cancer.

In addition, the CBD-treated skin samples had a reduction in the UVA-associated increase in the premutagenic marker 8-oxoguanine DNA glycosylase 1 and a reduction of two major UVA-induced mitochondrial DNA deletions associated with skin photoaging.

The research, Dr. Friedman noted, “took a village of collaborators and almost 3 years to pull together,” including collaborating with his long-standing mentor, Brian Berman, MD, PhD, professor emeritus of dermatology and dermatologic surgery at the University of Miami, Coral Gables, Florida, and a study coauthor. The study “demonstrated that purposeful delivery of CBD using an established nanoparticle platform ... can have a quantifiable impact on preventing the expected DNA damage and cellular injury one should see from UVA exposure,” said Dr. Friedman, who codeveloped the nanoparticle platform with his father, Joel M. Friedman, MD, PhD, professor of microbiology and immunology at Albert Einstein College of Medicine, New York City.

“Never before has a dermatologic study on topical cannabinoids dove so deeply into the biological impact of this natural ingredient to highlight its potential, here, as a mitigation strategy for unprotected exposure to prevent the downstream sequelae of UV radiation,” Dr. Friedman said.

In the paper, he and his coauthors acknowledged certain limitations of their study, including its small sample size and the single-center design.

Dr. Friedman disclosed that he coinvented the nanoparticle technology used in the trial. Dr. Berman is a consultant at MINO Labs, which funded the study. The remaining authors had no disclosures. The study was done in collaboration with the Center for Clinical and Cosmetic Research in Aventura, Florida.

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

Application of an investigative topical cannabidiol (CBD) cream to buttock skin demonstrated protective properties against ultraviolet A (UVA) radiation-induced DNA and mitochondrial DNA damage, results from a small prospective pilot study showed.

“This study hopefully reinvigorates interest in the utilization of whether it be plant-based, human-derived, or synthetic cannabinoids in the management of dermatologic disease,” one of the study investigators, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization. The study was published in the Journal of the American Academy of Dermatology.

George Washington University

For the prospective, single-center, pilot trial, which is believed to be the first of its kind, 19 volunteers aged 22-65 with Fitzpatrick skin types I-III applied either a nano-encapsulated CBD cream or a vehicle cream to blind spots on the skin of the buttocks twice daily for 14 days. Next, researchers applied a minimal erythema dose of UV radiation to the treated skin areas for 30 minutes. After 24 hours, they visually inspected the treated areas to clinically compare the erythema. They also performed five 4-mm punch biopsies from UVA- and non-UVA–exposed treatment sites on each buttock, as well as from an untreated control site that was at least 5 cm away from the treated left buttock.

At 24 hours, 21% of study participants showed less redness on CBD-treated skin compared with control-treated skin, while histology showed that CBD-treated skin demonstrated reduced UVA-induced epidermal hyperplasia compared with control-treated skin (a mean 11.3% change from baseline vs 28.7%, respectively; P = .01). In other findings, application of CBD cream reduced DNA damage and DNA mutations associated with UVA-induced skin aging/damage and ultimately skin cancer.

In addition, the CBD-treated skin samples had a reduction in the UVA-associated increase in the premutagenic marker 8-oxoguanine DNA glycosylase 1 and a reduction of two major UVA-induced mitochondrial DNA deletions associated with skin photoaging.

The research, Dr. Friedman noted, “took a village of collaborators and almost 3 years to pull together,” including collaborating with his long-standing mentor, Brian Berman, MD, PhD, professor emeritus of dermatology and dermatologic surgery at the University of Miami, Coral Gables, Florida, and a study coauthor. The study “demonstrated that purposeful delivery of CBD using an established nanoparticle platform ... can have a quantifiable impact on preventing the expected DNA damage and cellular injury one should see from UVA exposure,” said Dr. Friedman, who codeveloped the nanoparticle platform with his father, Joel M. Friedman, MD, PhD, professor of microbiology and immunology at Albert Einstein College of Medicine, New York City.

“Never before has a dermatologic study on topical cannabinoids dove so deeply into the biological impact of this natural ingredient to highlight its potential, here, as a mitigation strategy for unprotected exposure to prevent the downstream sequelae of UV radiation,” Dr. Friedman said.

In the paper, he and his coauthors acknowledged certain limitations of their study, including its small sample size and the single-center design.

Dr. Friedman disclosed that he coinvented the nanoparticle technology used in the trial. Dr. Berman is a consultant at MINO Labs, which funded the study. The remaining authors had no disclosures. The study was done in collaboration with the Center for Clinical and Cosmetic Research in Aventura, Florida.

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

Application of an investigative topical cannabidiol (CBD) cream to buttock skin demonstrated protective properties against ultraviolet A (UVA) radiation-induced DNA and mitochondrial DNA damage, results from a small prospective pilot study showed.

“This study hopefully reinvigorates interest in the utilization of whether it be plant-based, human-derived, or synthetic cannabinoids in the management of dermatologic disease,” one of the study investigators, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization. The study was published in the Journal of the American Academy of Dermatology.

George Washington University

For the prospective, single-center, pilot trial, which is believed to be the first of its kind, 19 volunteers aged 22-65 with Fitzpatrick skin types I-III applied either a nano-encapsulated CBD cream or a vehicle cream to blind spots on the skin of the buttocks twice daily for 14 days. Next, researchers applied a minimal erythema dose of UV radiation to the treated skin areas for 30 minutes. After 24 hours, they visually inspected the treated areas to clinically compare the erythema. They also performed five 4-mm punch biopsies from UVA- and non-UVA–exposed treatment sites on each buttock, as well as from an untreated control site that was at least 5 cm away from the treated left buttock.

At 24 hours, 21% of study participants showed less redness on CBD-treated skin compared with control-treated skin, while histology showed that CBD-treated skin demonstrated reduced UVA-induced epidermal hyperplasia compared with control-treated skin (a mean 11.3% change from baseline vs 28.7%, respectively; P = .01). In other findings, application of CBD cream reduced DNA damage and DNA mutations associated with UVA-induced skin aging/damage and ultimately skin cancer.

In addition, the CBD-treated skin samples had a reduction in the UVA-associated increase in the premutagenic marker 8-oxoguanine DNA glycosylase 1 and a reduction of two major UVA-induced mitochondrial DNA deletions associated with skin photoaging.

The research, Dr. Friedman noted, “took a village of collaborators and almost 3 years to pull together,” including collaborating with his long-standing mentor, Brian Berman, MD, PhD, professor emeritus of dermatology and dermatologic surgery at the University of Miami, Coral Gables, Florida, and a study coauthor. The study “demonstrated that purposeful delivery of CBD using an established nanoparticle platform ... can have a quantifiable impact on preventing the expected DNA damage and cellular injury one should see from UVA exposure,” said Dr. Friedman, who codeveloped the nanoparticle platform with his father, Joel M. Friedman, MD, PhD, professor of microbiology and immunology at Albert Einstein College of Medicine, New York City.

“Never before has a dermatologic study on topical cannabinoids dove so deeply into the biological impact of this natural ingredient to highlight its potential, here, as a mitigation strategy for unprotected exposure to prevent the downstream sequelae of UV radiation,” Dr. Friedman said.

In the paper, he and his coauthors acknowledged certain limitations of their study, including its small sample size and the single-center design.

Dr. Friedman disclosed that he coinvented the nanoparticle technology used in the trial. Dr. Berman is a consultant at MINO Labs, which funded the study. The remaining authors had no disclosures. The study was done in collaboration with the Center for Clinical and Cosmetic Research in Aventura, Florida.

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

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

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

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

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

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

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

TOPLINE:

Higher energy intake and glycemic load in the late morning are associated with a lower risk for type 2 diabetes (T2D) in Hispanic/Latino adults.

METHODOLOGY:

• Glucose tolerance peaks in the morning and declines in the afternoon and evening in individuals without diabetes.
• Researchers conducted a prospective cohort study enrolling 8868 Hispanic/Latino adults (mean age, 38.7 years; 51.5% women) without diabetes across four US communities between 2008 and 2011, with a second clinic examination conducted between 2014 and 2017.
• Meal timing was categorized into five periods: Early morning (6:00-8:59 AM), late morning (9:00-11:59 AM), afternoon (12:00-5:59 PM), evening (6:00-11:59 PM), and night (0:00-5:59 AM).
• Participants’ energy intake and glycemic load for each period were assessed at baseline using two 24-hour dietary recalls.
• Incident diabetes was identified through annual follow-up calls or at the second clinic examination.

TAKEAWAY:

• Each 100-kcal increment in energy intake and 10-unit increment in glycemic load in the late morning was associated with a 6% and 7% lower risk for T2D, respectively (both P = .001), independent of total energy intake, diet quality, and other confounders.
• No such association was found between energy intake and glycemic load in early morning, afternoon, evening, or night meal timings and the risk for diabetes.
• Substituting 100 kcal of energy intake from the early morning, afternoon, or evening with late-morning equivalents was associated with a 5% lower risk for diabetes (all P < .05).
• Similarly, substituting 10 units of energy-adjusted glycemic load from the early morning, afternoon, or evening with late-morning equivalents yielded a 7%-9% lower risk for diabetes (all P < .05).

IN PRACTICE:

“Our findings further enhance the existing literature by demonstrating the potential long-term promise of eating in alignment with the diurnal rhythm of glucose tolerance for diabetes prevention,” the authors wrote.

SOURCE:

The study was led by Jin Dai, PhD, Fielding School of Public Health, University of California, Los Angeles. It was published online in Diabetes Care.

LIMITATIONS:

The study’s reliance on only two 24-hour self-reported dietary recalls may have introduced measurement error. Diabetes was self-reported, which may have led to outcome misclassification. The study’s relatively short follow-up time may have introduced reverse causation bias. As most patients had T2D, the findings predominately apply to this diabetes subtype. 

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.

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

TOPLINE:

Higher energy intake and glycemic load in the late morning are associated with a lower risk for type 2 diabetes (T2D) in Hispanic/Latino adults.

METHODOLOGY:

• Glucose tolerance peaks in the morning and declines in the afternoon and evening in individuals without diabetes.
• Researchers conducted a prospective cohort study enrolling 8868 Hispanic/Latino adults (mean age, 38.7 years; 51.5% women) without diabetes across four US communities between 2008 and 2011, with a second clinic examination conducted between 2014 and 2017.
• Meal timing was categorized into five periods: Early morning (6:00-8:59 AM), late morning (9:00-11:59 AM), afternoon (12:00-5:59 PM), evening (6:00-11:59 PM), and night (0:00-5:59 AM).
• Participants’ energy intake and glycemic load for each period were assessed at baseline using two 24-hour dietary recalls.
• Incident diabetes was identified through annual follow-up calls or at the second clinic examination.

TAKEAWAY:

• Each 100-kcal increment in energy intake and 10-unit increment in glycemic load in the late morning was associated with a 6% and 7% lower risk for T2D, respectively (both P = .001), independent of total energy intake, diet quality, and other confounders.
• No such association was found between energy intake and glycemic load in early morning, afternoon, evening, or night meal timings and the risk for diabetes.
• Substituting 100 kcal of energy intake from the early morning, afternoon, or evening with late-morning equivalents was associated with a 5% lower risk for diabetes (all P < .05).
• Similarly, substituting 10 units of energy-adjusted glycemic load from the early morning, afternoon, or evening with late-morning equivalents yielded a 7%-9% lower risk for diabetes (all P < .05).

IN PRACTICE:

“Our findings further enhance the existing literature by demonstrating the potential long-term promise of eating in alignment with the diurnal rhythm of glucose tolerance for diabetes prevention,” the authors wrote.

SOURCE:

The study was led by Jin Dai, PhD, Fielding School of Public Health, University of California, Los Angeles. It was published online in Diabetes Care.

LIMITATIONS:

The study’s reliance on only two 24-hour self-reported dietary recalls may have introduced measurement error. Diabetes was self-reported, which may have led to outcome misclassification. The study’s relatively short follow-up time may have introduced reverse causation bias. As most patients had T2D, the findings predominately apply to this diabetes subtype. 

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.

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

TOPLINE:

Higher energy intake and glycemic load in the late morning are associated with a lower risk for type 2 diabetes (T2D) in Hispanic/Latino adults.

METHODOLOGY:

• Glucose tolerance peaks in the morning and declines in the afternoon and evening in individuals without diabetes.
• Researchers conducted a prospective cohort study enrolling 8868 Hispanic/Latino adults (mean age, 38.7 years; 51.5% women) without diabetes across four US communities between 2008 and 2011, with a second clinic examination conducted between 2014 and 2017.
• Meal timing was categorized into five periods: Early morning (6:00-8:59 AM), late morning (9:00-11:59 AM), afternoon (12:00-5:59 PM), evening (6:00-11:59 PM), and night (0:00-5:59 AM).
• Participants’ energy intake and glycemic load for each period were assessed at baseline using two 24-hour dietary recalls.
• Incident diabetes was identified through annual follow-up calls or at the second clinic examination.

TAKEAWAY:

• Each 100-kcal increment in energy intake and 10-unit increment in glycemic load in the late morning was associated with a 6% and 7% lower risk for T2D, respectively (both P = .001), independent of total energy intake, diet quality, and other confounders.
• No such association was found between energy intake and glycemic load in early morning, afternoon, evening, or night meal timings and the risk for diabetes.
• Substituting 100 kcal of energy intake from the early morning, afternoon, or evening with late-morning equivalents was associated with a 5% lower risk for diabetes (all P < .05).
• Similarly, substituting 10 units of energy-adjusted glycemic load from the early morning, afternoon, or evening with late-morning equivalents yielded a 7%-9% lower risk for diabetes (all P < .05).

IN PRACTICE:

“Our findings further enhance the existing literature by demonstrating the potential long-term promise of eating in alignment with the diurnal rhythm of glucose tolerance for diabetes prevention,” the authors wrote.

SOURCE:

The study was led by Jin Dai, PhD, Fielding School of Public Health, University of California, Los Angeles. It was published online in Diabetes Care.

LIMITATIONS:

The study’s reliance on only two 24-hour self-reported dietary recalls may have introduced measurement error. Diabetes was self-reported, which may have led to outcome misclassification. The study’s relatively short follow-up time may have introduced reverse causation bias. As most patients had T2D, the findings predominately apply to this diabetes subtype. 

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.

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

TOPLINE:

Patients with metastatic hormone-sensitive prostate cancer and baseline bone pain at diagnosis have worse overall survival compared to those without bone pain, a post hoc study found.

METHODOLOGY:

• Prostate cancer often metastasizes to the bones, leading to pain and a reduced quality of life. While the relationship between bone pain and overall survival in metastatic, castration-resistant prostate cancer is well-documented, its impact in metastatic hormone-sensitive prostate cancer is less clear.
• Researchers conducted a post hoc secondary analysis using data from the SWOG-1216 phase 3 randomized clinical trial, which included 1279 men diagnosed with metastatic hormone-sensitive prostate cancer from 248 centers across the United States. Patients had received androgen deprivation therapy either with orteronel or bicalutamide.
• Among the 1197 patients (median age, 67.6 years) with data on bone pain included in the secondary analysis, 301 (23.5%) reported bone pain at baseline.
• The primary outcome was overall survival; secondary outcomes included progression-free survival and prostate-specific antigen response.

TAKEAWAY:

• The median overall survival for patients with baseline bone pain was 3.9 years compared with not reached (95% CI, 6.6 years to not reached) for those without bone pain at a median follow-up of 4 years (adjusted hazard ratio [aHR], 1.66; P < .001).
• Similarly, patients with bone pain had a shorter progression-free survival vs those without bone pain (median, 1.3 years vs 3.7 years; aHR, 1.46; P < .001).
• The complete prostate-specific antigen response rate at 7 months was also lower for patients with baseline bone pain (46.3% vs 66.3%; P < .001).

IN PRACTICE:

Patients with metastatic hormone-sensitive prostate cancer “with baseline bone pain had worse survival outcomes than those without baseline bone pain,” the authors wrote. “These results highlight the need to consider bone pain in prognostic modeling, treatment selection, patient monitoring, and follow-up and suggest prioritizing these patients for clinical trials and immediate systemic treatment initiation.”

SOURCE:

The study, led by Georges Gebrael, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, was published online in JAMA Network Open.

LIMITATIONS:

The post hoc design may introduce bias. Orteronel failed to receive regulatory approval, which may affect the generalizability of the findings. In addition, the study did not account for synchronous vs metachronous disease status, a known established prognostic factor.

DISCLOSURES:

The study was funded by the National Institutes of Health/National Cancer Institute and Millennium Pharmaceuticals (Takeda Oncology Company). Several authors declared ties with various sources.

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

TOPLINE:

Patients with metastatic hormone-sensitive prostate cancer and baseline bone pain at diagnosis have worse overall survival compared to those without bone pain, a post hoc study found.

METHODOLOGY:

• Prostate cancer often metastasizes to the bones, leading to pain and a reduced quality of life. While the relationship between bone pain and overall survival in metastatic, castration-resistant prostate cancer is well-documented, its impact in metastatic hormone-sensitive prostate cancer is less clear.
• Researchers conducted a post hoc secondary analysis using data from the SWOG-1216 phase 3 randomized clinical trial, which included 1279 men diagnosed with metastatic hormone-sensitive prostate cancer from 248 centers across the United States. Patients had received androgen deprivation therapy either with orteronel or bicalutamide.
• Among the 1197 patients (median age, 67.6 years) with data on bone pain included in the secondary analysis, 301 (23.5%) reported bone pain at baseline.
• The primary outcome was overall survival; secondary outcomes included progression-free survival and prostate-specific antigen response.

TAKEAWAY:

• The median overall survival for patients with baseline bone pain was 3.9 years compared with not reached (95% CI, 6.6 years to not reached) for those without bone pain at a median follow-up of 4 years (adjusted hazard ratio [aHR], 1.66; P < .001).
• Similarly, patients with bone pain had a shorter progression-free survival vs those without bone pain (median, 1.3 years vs 3.7 years; aHR, 1.46; P < .001).
• The complete prostate-specific antigen response rate at 7 months was also lower for patients with baseline bone pain (46.3% vs 66.3%; P < .001).

IN PRACTICE:

Patients with metastatic hormone-sensitive prostate cancer “with baseline bone pain had worse survival outcomes than those without baseline bone pain,” the authors wrote. “These results highlight the need to consider bone pain in prognostic modeling, treatment selection, patient monitoring, and follow-up and suggest prioritizing these patients for clinical trials and immediate systemic treatment initiation.”

SOURCE:

The study, led by Georges Gebrael, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, was published online in JAMA Network Open.

LIMITATIONS:

The post hoc design may introduce bias. Orteronel failed to receive regulatory approval, which may affect the generalizability of the findings. In addition, the study did not account for synchronous vs metachronous disease status, a known established prognostic factor.

DISCLOSURES:

The study was funded by the National Institutes of Health/National Cancer Institute and Millennium Pharmaceuticals (Takeda Oncology Company). Several authors declared ties with various sources.

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

TOPLINE:

Patients with metastatic hormone-sensitive prostate cancer and baseline bone pain at diagnosis have worse overall survival compared to those without bone pain, a post hoc study found.

METHODOLOGY:

• Prostate cancer often metastasizes to the bones, leading to pain and a reduced quality of life. While the relationship between bone pain and overall survival in metastatic, castration-resistant prostate cancer is well-documented, its impact in metastatic hormone-sensitive prostate cancer is less clear.
• Researchers conducted a post hoc secondary analysis using data from the SWOG-1216 phase 3 randomized clinical trial, which included 1279 men diagnosed with metastatic hormone-sensitive prostate cancer from 248 centers across the United States. Patients had received androgen deprivation therapy either with orteronel or bicalutamide.
• Among the 1197 patients (median age, 67.6 years) with data on bone pain included in the secondary analysis, 301 (23.5%) reported bone pain at baseline.
• The primary outcome was overall survival; secondary outcomes included progression-free survival and prostate-specific antigen response.

TAKEAWAY:

• The median overall survival for patients with baseline bone pain was 3.9 years compared with not reached (95% CI, 6.6 years to not reached) for those without bone pain at a median follow-up of 4 years (adjusted hazard ratio [aHR], 1.66; P < .001).
• Similarly, patients with bone pain had a shorter progression-free survival vs those without bone pain (median, 1.3 years vs 3.7 years; aHR, 1.46; P < .001).
• The complete prostate-specific antigen response rate at 7 months was also lower for patients with baseline bone pain (46.3% vs 66.3%; P < .001).

IN PRACTICE:

Patients with metastatic hormone-sensitive prostate cancer “with baseline bone pain had worse survival outcomes than those without baseline bone pain,” the authors wrote. “These results highlight the need to consider bone pain in prognostic modeling, treatment selection, patient monitoring, and follow-up and suggest prioritizing these patients for clinical trials and immediate systemic treatment initiation.”

SOURCE:

The study, led by Georges Gebrael, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, was published online in JAMA Network Open.

LIMITATIONS:

The post hoc design may introduce bias. Orteronel failed to receive regulatory approval, which may affect the generalizability of the findings. In addition, the study did not account for synchronous vs metachronous disease status, a known established prognostic factor.

DISCLOSURES:

The study was funded by the National Institutes of Health/National Cancer Institute and Millennium Pharmaceuticals (Takeda Oncology Company). Several authors declared ties with various sources.

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

Recognizing the increasing importance of digital pathology and its potential impact to transform federal health care, government, military, and university digital pathology specialists convened in May 2023 to share expertise to advance the use of digital pathology in federal health care. 

The seminar was hosted by the University of Pittsburgh and led by Ronald Poropatich, MD, Director of the Center for Military Medicine Research, Health Sciences, and Professor of Medicine at the University of Pittsburgh Medical Center, and Douglas Hartman, MD, Vice Chair of Pathology Informatics, Associate Director of the Center for AI Innovation in Medical Imaging, and Professor of Pathology at the University of Pittsburgh/University of Pittsburgh Medical Center (UPMC).

Invitees included senior federal government pathologists, laboratory scientists, IT leaders, and stakeholders from the VA, DoD, HHS (NIH, CDC, IHS, FDA) and other federal agencies. The speakers for the conference were CDR Roger Boodoo, MD, Chief of Innovation, Defense Health Agency; Ryan Collins, MD, Pathologist, Williamsport Pathology Association; Pat Flanders, Chief Information Officer, J6, Defense Health Agency; Matthew Hanna, MD, Director, Digital Pathology Informatics, Memorial Sloan Kettering Cancer Center; Stephanie Harmon, PhD, Staff Scientist, NIH NCI, Imaging/Data Scientist in Molecular Imaging; Douglas Hartman, MD, Vice Chair of Pathology Informatics, University of Pittsburgh; Stephen Hewitt, MD, PhD, Head, Experimental Pathology Laboratory, NIH NCI, Center for Cancer Research; Jason Hipp, MD, PhD, Chief Digital Innovation Officer, Mayo Collaborate Services,  Mayo Clinic; Brian Lein, MD, Assistant Director, Healthcare Administration, Defense Health Agency; Col Mark Lyman, MD, Pathology Consultant to the US Air Force Surgeon General; COL Joel Moncur, MD, Director, Joint Pathology Center; Ronald Poropatich, MD, Director of the Center for Military Medicine Research, Health Sciences; Professor of Medicine, University of Pittsburgh; David Shulkin, MD, Ninth U.S. Secretary of Veterans Affairs; Eliot Siegel, MD, Chief of Radiology and Nuclear Medicine, Veterans Affairs Maryland Healthcare System; Professor and Vice Chair, University of Maryland School of Medicine; CDR Jenny Smith, DO, Pathologist, US Naval Medical Center Portsmouth; Shandong Wu, PhD, Associate Professor, Departments of Radiology, Biomedical Informatics, and Bioengineering, Director of Center for Artificial Intelligence Innovation in Medical Imaging, University of Pittsburgh; LCDR Victoria Mahar MD, Pathologist, US Army. 

Throughout the 1.5-day meeting, topics such as the integration of systems, the value of single vendor solutions vs multiple vendors, and the interconnectedness of radiology and pathology in health care were discussed. The speakers addressed the challenges of adopting digital pathology, including workflow improvement, quality control, and the generalizability of algorithms. The importance of collaboration, leadership, data analytics, compliance with clinical practice guidelines, and research and development efforts were stressed. The increasingly important role of artificial intelligence (AI) in digital pathology, its applications, and its benefits were also highlighted. Continuing education credits were offered to participants. 

Overall, the meeting provided valuable insights into the advancements, challenges, and potential of digital pathology, AI, and technology integration in the federal health care ecosystem. However, this cannot be achieved without leadership from and close collaboration between key industry, academic, and government stakeholders.

Uses of Digital Pathology

Digital pathology refers to the practice of digitizing glass slides containing tissue samples and using digital imaging technology to analyze and interpret them. It involves capturing high-resolution images of microscopic slides and storing them in a digital format. These digitized images can be accessed and analyzed using computer-based tools and software.

While traditional pathology involves examining tissue samples under a microscope to make diagnoses and provide insights into diseases and conditions, digital pathology uses digital scanners that capture all relevant tissue on the glass slide at high magnification. This process generates a high-fidelity digital representation of the tissue sample that can be navigated akin to how glass slides are reviewed on a brightfield microscope in current practice (eg, panning, zooming, etc). Microscopic review of patient specimens in pathology allows for identifying patterns and markers that may not be easily detectable with manual examination alone. 

The digitized slides can be stored in a database or a slide management system, allowing pathologists and other healthcare professionals to access and review them remotely, thus creating the potential to improve collaboration among pathologists, facilitate second opinions, and enable easier access to archived slides for research purposes. 

Potential Benefits

Digital pathology also opens the door to advanced image analysis techniques, such as computer-aided diagnosis, machine learning, and AI algorithms, with the potential for the following outcomes and benefits:

• Improved accuracy AI algorithms can analyze large volumes of digital pathology data with great precision, reducing the chances of human error and subjective interpretation. This can lead to more accurate and consistent diagnoses, especially in challenging cases where subtle patterns or features may be difficult to detect.
• Automated detection and classification AI algorithms can be trained to detect and classify specific features or abnormalities in digital pathology images. For example, AI models can identify cancerous cells, tissue patterns associated with different diseases, or specific biomarkers. This can assist pathologists in diagnosing diseases more accurately and efficiently.
• Quantitative analysis AI can analyze large quantities of digital pathology data and extract quantitative measurements. For instance, it can calculate the percentage of tumor cells in a sample, assess the density of immune cells, or measure the extent of tissue damage. These objective measurements can aid in prognosis prediction and treatment planning.
• Image segmentation AI algorithms can segment digital pathology images into different regions or structures, such as nuclei, cytoplasm, or blood vessels. This segmentation allows for precise analysis and extraction of features for further study. It can also facilitate the identification of specific cell types or tissue components.
• Image enhancement AI techniques can enhance the quality of digital pathology images by improving clarity and reducing noise or artifacts. This can help pathologists visualize and interpret slides more effectively, especially in challenging cases with low-quality or complex images.
• Decision support systems AI-powered decision support systems can assist pathologists by providing recommendations or second opinions based on the analysis of digital pathology data. These systems can offer insights, suggest potential diagnoses, or provide relevant research references, augmenting the pathologist’s expertise and improving diagnostic accuracy.
• Collaboration and second opinions Digital pathology, combined with AI, facilitates remote access to digitized slides, enabling pathologists to seek second opinions or collaborate with experts from around the world. This can enhance the quality of diagnoses by leveraging the collective expertise of pathologists and fostering knowledge sharing.
• Education and training AI algorithms can be utilized in virtual microscopy platforms to create interactive and educational experiences. Pathology residents and students can learn from annotated cases, receive real-time feedback, and develop their skills in a digital environment.
• Research and discovery AI can assist in identifying patterns, correlations, and novel biomarkers in digital pathology data. By analyzing large datasets, AI algorithms can help uncover new insights, contribute to research advancements, and aid in the development of personalized medicine approaches.
• Predictive modeling AI can analyze vast amounts of digital pathology data, patient records, and outcomes to develop predictive models. These models can estimate disease progression, treatment response, or patient survival rates based on various factors. They can contribute to personalized medicine by assisting in treatment decisions and prognosis assessment.

It is important to note that while AI has shown promising results, it is not intended to replace human pathologists but to augment their capabilities. Overall, the combination of AI technology with the expertise of pathologists can lead to improved diagnosis, better patient care, and more efficient workflows in digital pathology.
 

Recognizing the increasing importance of digital pathology and its potential impact to transform federal health care, government, military, and university digital pathology specialists convened in May 2023 to share expertise to advance the use of digital pathology in federal health care. 

The seminar was hosted by the University of Pittsburgh and led by Ronald Poropatich, MD, Director of the Center for Military Medicine Research, Health Sciences, and Professor of Medicine at the University of Pittsburgh Medical Center, and Douglas Hartman, MD, Vice Chair of Pathology Informatics, Associate Director of the Center for AI Innovation in Medical Imaging, and Professor of Pathology at the University of Pittsburgh/University of Pittsburgh Medical Center (UPMC).

Invitees included senior federal government pathologists, laboratory scientists, IT leaders, and stakeholders from the VA, DoD, HHS (NIH, CDC, IHS, FDA) and other federal agencies. The speakers for the conference were CDR Roger Boodoo, MD, Chief of Innovation, Defense Health Agency; Ryan Collins, MD, Pathologist, Williamsport Pathology Association; Pat Flanders, Chief Information Officer, J6, Defense Health Agency; Matthew Hanna, MD, Director, Digital Pathology Informatics, Memorial Sloan Kettering Cancer Center; Stephanie Harmon, PhD, Staff Scientist, NIH NCI, Imaging/Data Scientist in Molecular Imaging; Douglas Hartman, MD, Vice Chair of Pathology Informatics, University of Pittsburgh; Stephen Hewitt, MD, PhD, Head, Experimental Pathology Laboratory, NIH NCI, Center for Cancer Research; Jason Hipp, MD, PhD, Chief Digital Innovation Officer, Mayo Collaborate Services,  Mayo Clinic; Brian Lein, MD, Assistant Director, Healthcare Administration, Defense Health Agency; Col Mark Lyman, MD, Pathology Consultant to the US Air Force Surgeon General; COL Joel Moncur, MD, Director, Joint Pathology Center; Ronald Poropatich, MD, Director of the Center for Military Medicine Research, Health Sciences; Professor of Medicine, University of Pittsburgh; David Shulkin, MD, Ninth U.S. Secretary of Veterans Affairs; Eliot Siegel, MD, Chief of Radiology and Nuclear Medicine, Veterans Affairs Maryland Healthcare System; Professor and Vice Chair, University of Maryland School of Medicine; CDR Jenny Smith, DO, Pathologist, US Naval Medical Center Portsmouth; Shandong Wu, PhD, Associate Professor, Departments of Radiology, Biomedical Informatics, and Bioengineering, Director of Center for Artificial Intelligence Innovation in Medical Imaging, University of Pittsburgh; LCDR Victoria Mahar MD, Pathologist, US Army. 

Throughout the 1.5-day meeting, topics such as the integration of systems, the value of single vendor solutions vs multiple vendors, and the interconnectedness of radiology and pathology in health care were discussed. The speakers addressed the challenges of adopting digital pathology, including workflow improvement, quality control, and the generalizability of algorithms. The importance of collaboration, leadership, data analytics, compliance with clinical practice guidelines, and research and development efforts were stressed. The increasingly important role of artificial intelligence (AI) in digital pathology, its applications, and its benefits were also highlighted. Continuing education credits were offered to participants. 

Overall, the meeting provided valuable insights into the advancements, challenges, and potential of digital pathology, AI, and technology integration in the federal health care ecosystem. However, this cannot be achieved without leadership from and close collaboration between key industry, academic, and government stakeholders.

Uses of Digital Pathology

Digital pathology refers to the practice of digitizing glass slides containing tissue samples and using digital imaging technology to analyze and interpret them. It involves capturing high-resolution images of microscopic slides and storing them in a digital format. These digitized images can be accessed and analyzed using computer-based tools and software.

While traditional pathology involves examining tissue samples under a microscope to make diagnoses and provide insights into diseases and conditions, digital pathology uses digital scanners that capture all relevant tissue on the glass slide at high magnification. This process generates a high-fidelity digital representation of the tissue sample that can be navigated akin to how glass slides are reviewed on a brightfield microscope in current practice (eg, panning, zooming, etc). Microscopic review of patient specimens in pathology allows for identifying patterns and markers that may not be easily detectable with manual examination alone. 

The digitized slides can be stored in a database or a slide management system, allowing pathologists and other healthcare professionals to access and review them remotely, thus creating the potential to improve collaboration among pathologists, facilitate second opinions, and enable easier access to archived slides for research purposes. 

Potential Benefits

Digital pathology also opens the door to advanced image analysis techniques, such as computer-aided diagnosis, machine learning, and AI algorithms, with the potential for the following outcomes and benefits:

• Improved accuracy AI algorithms can analyze large volumes of digital pathology data with great precision, reducing the chances of human error and subjective interpretation. This can lead to more accurate and consistent diagnoses, especially in challenging cases where subtle patterns or features may be difficult to detect.
• Automated detection and classification AI algorithms can be trained to detect and classify specific features or abnormalities in digital pathology images. For example, AI models can identify cancerous cells, tissue patterns associated with different diseases, or specific biomarkers. This can assist pathologists in diagnosing diseases more accurately and efficiently.
• Quantitative analysis AI can analyze large quantities of digital pathology data and extract quantitative measurements. For instance, it can calculate the percentage of tumor cells in a sample, assess the density of immune cells, or measure the extent of tissue damage. These objective measurements can aid in prognosis prediction and treatment planning.
• Image segmentation AI algorithms can segment digital pathology images into different regions or structures, such as nuclei, cytoplasm, or blood vessels. This segmentation allows for precise analysis and extraction of features for further study. It can also facilitate the identification of specific cell types or tissue components.
• Image enhancement AI techniques can enhance the quality of digital pathology images by improving clarity and reducing noise or artifacts. This can help pathologists visualize and interpret slides more effectively, especially in challenging cases with low-quality or complex images.
• Decision support systems AI-powered decision support systems can assist pathologists by providing recommendations or second opinions based on the analysis of digital pathology data. These systems can offer insights, suggest potential diagnoses, or provide relevant research references, augmenting the pathologist’s expertise and improving diagnostic accuracy.
• Collaboration and second opinions Digital pathology, combined with AI, facilitates remote access to digitized slides, enabling pathologists to seek second opinions or collaborate with experts from around the world. This can enhance the quality of diagnoses by leveraging the collective expertise of pathologists and fostering knowledge sharing.
• Education and training AI algorithms can be utilized in virtual microscopy platforms to create interactive and educational experiences. Pathology residents and students can learn from annotated cases, receive real-time feedback, and develop their skills in a digital environment.
• Research and discovery AI can assist in identifying patterns, correlations, and novel biomarkers in digital pathology data. By analyzing large datasets, AI algorithms can help uncover new insights, contribute to research advancements, and aid in the development of personalized medicine approaches.
• Predictive modeling AI can analyze vast amounts of digital pathology data, patient records, and outcomes to develop predictive models. These models can estimate disease progression, treatment response, or patient survival rates based on various factors. They can contribute to personalized medicine by assisting in treatment decisions and prognosis assessment.

It is important to note that while AI has shown promising results, it is not intended to replace human pathologists but to augment their capabilities. Overall, the combination of AI technology with the expertise of pathologists can lead to improved diagnosis, better patient care, and more efficient workflows in digital pathology.
 

Recognizing the increasing importance of digital pathology and its potential impact to transform federal health care, government, military, and university digital pathology specialists convened in May 2023 to share expertise to advance the use of digital pathology in federal health care. 

The seminar was hosted by the University of Pittsburgh and led by Ronald Poropatich, MD, Director of the Center for Military Medicine Research, Health Sciences, and Professor of Medicine at the University of Pittsburgh Medical Center, and Douglas Hartman, MD, Vice Chair of Pathology Informatics, Associate Director of the Center for AI Innovation in Medical Imaging, and Professor of Pathology at the University of Pittsburgh/University of Pittsburgh Medical Center (UPMC).

Invitees included senior federal government pathologists, laboratory scientists, IT leaders, and stakeholders from the VA, DoD, HHS (NIH, CDC, IHS, FDA) and other federal agencies. The speakers for the conference were CDR Roger Boodoo, MD, Chief of Innovation, Defense Health Agency; Ryan Collins, MD, Pathologist, Williamsport Pathology Association; Pat Flanders, Chief Information Officer, J6, Defense Health Agency; Matthew Hanna, MD, Director, Digital Pathology Informatics, Memorial Sloan Kettering Cancer Center; Stephanie Harmon, PhD, Staff Scientist, NIH NCI, Imaging/Data Scientist in Molecular Imaging; Douglas Hartman, MD, Vice Chair of Pathology Informatics, University of Pittsburgh; Stephen Hewitt, MD, PhD, Head, Experimental Pathology Laboratory, NIH NCI, Center for Cancer Research; Jason Hipp, MD, PhD, Chief Digital Innovation Officer, Mayo Collaborate Services,  Mayo Clinic; Brian Lein, MD, Assistant Director, Healthcare Administration, Defense Health Agency; Col Mark Lyman, MD, Pathology Consultant to the US Air Force Surgeon General; COL Joel Moncur, MD, Director, Joint Pathology Center; Ronald Poropatich, MD, Director of the Center for Military Medicine Research, Health Sciences; Professor of Medicine, University of Pittsburgh; David Shulkin, MD, Ninth U.S. Secretary of Veterans Affairs; Eliot Siegel, MD, Chief of Radiology and Nuclear Medicine, Veterans Affairs Maryland Healthcare System; Professor and Vice Chair, University of Maryland School of Medicine; CDR Jenny Smith, DO, Pathologist, US Naval Medical Center Portsmouth; Shandong Wu, PhD, Associate Professor, Departments of Radiology, Biomedical Informatics, and Bioengineering, Director of Center for Artificial Intelligence Innovation in Medical Imaging, University of Pittsburgh; LCDR Victoria Mahar MD, Pathologist, US Army. 

Throughout the 1.5-day meeting, topics such as the integration of systems, the value of single vendor solutions vs multiple vendors, and the interconnectedness of radiology and pathology in health care were discussed. The speakers addressed the challenges of adopting digital pathology, including workflow improvement, quality control, and the generalizability of algorithms. The importance of collaboration, leadership, data analytics, compliance with clinical practice guidelines, and research and development efforts were stressed. The increasingly important role of artificial intelligence (AI) in digital pathology, its applications, and its benefits were also highlighted. Continuing education credits were offered to participants. 

Overall, the meeting provided valuable insights into the advancements, challenges, and potential of digital pathology, AI, and technology integration in the federal health care ecosystem. However, this cannot be achieved without leadership from and close collaboration between key industry, academic, and government stakeholders.

Uses of Digital Pathology

Digital pathology refers to the practice of digitizing glass slides containing tissue samples and using digital imaging technology to analyze and interpret them. It involves capturing high-resolution images of microscopic slides and storing them in a digital format. These digitized images can be accessed and analyzed using computer-based tools and software.

While traditional pathology involves examining tissue samples under a microscope to make diagnoses and provide insights into diseases and conditions, digital pathology uses digital scanners that capture all relevant tissue on the glass slide at high magnification. This process generates a high-fidelity digital representation of the tissue sample that can be navigated akin to how glass slides are reviewed on a brightfield microscope in current practice (eg, panning, zooming, etc). Microscopic review of patient specimens in pathology allows for identifying patterns and markers that may not be easily detectable with manual examination alone. 

The digitized slides can be stored in a database or a slide management system, allowing pathologists and other healthcare professionals to access and review them remotely, thus creating the potential to improve collaboration among pathologists, facilitate second opinions, and enable easier access to archived slides for research purposes. 

Potential Benefits

Digital pathology also opens the door to advanced image analysis techniques, such as computer-aided diagnosis, machine learning, and AI algorithms, with the potential for the following outcomes and benefits:

• Improved accuracy AI algorithms can analyze large volumes of digital pathology data with great precision, reducing the chances of human error and subjective interpretation. This can lead to more accurate and consistent diagnoses, especially in challenging cases where subtle patterns or features may be difficult to detect.
• Automated detection and classification AI algorithms can be trained to detect and classify specific features or abnormalities in digital pathology images. For example, AI models can identify cancerous cells, tissue patterns associated with different diseases, or specific biomarkers. This can assist pathologists in diagnosing diseases more accurately and efficiently.
• Quantitative analysis AI can analyze large quantities of digital pathology data and extract quantitative measurements. For instance, it can calculate the percentage of tumor cells in a sample, assess the density of immune cells, or measure the extent of tissue damage. These objective measurements can aid in prognosis prediction and treatment planning.
• Image segmentation AI algorithms can segment digital pathology images into different regions or structures, such as nuclei, cytoplasm, or blood vessels. This segmentation allows for precise analysis and extraction of features for further study. It can also facilitate the identification of specific cell types or tissue components.
• Image enhancement AI techniques can enhance the quality of digital pathology images by improving clarity and reducing noise or artifacts. This can help pathologists visualize and interpret slides more effectively, especially in challenging cases with low-quality or complex images.
• Decision support systems AI-powered decision support systems can assist pathologists by providing recommendations or second opinions based on the analysis of digital pathology data. These systems can offer insights, suggest potential diagnoses, or provide relevant research references, augmenting the pathologist’s expertise and improving diagnostic accuracy.
• Collaboration and second opinions Digital pathology, combined with AI, facilitates remote access to digitized slides, enabling pathologists to seek second opinions or collaborate with experts from around the world. This can enhance the quality of diagnoses by leveraging the collective expertise of pathologists and fostering knowledge sharing.
• Education and training AI algorithms can be utilized in virtual microscopy platforms to create interactive and educational experiences. Pathology residents and students can learn from annotated cases, receive real-time feedback, and develop their skills in a digital environment.
• Research and discovery AI can assist in identifying patterns, correlations, and novel biomarkers in digital pathology data. By analyzing large datasets, AI algorithms can help uncover new insights, contribute to research advancements, and aid in the development of personalized medicine approaches.
• Predictive modeling AI can analyze vast amounts of digital pathology data, patient records, and outcomes to develop predictive models. These models can estimate disease progression, treatment response, or patient survival rates based on various factors. They can contribute to personalized medicine by assisting in treatment decisions and prognosis assessment.

It is important to note that while AI has shown promising results, it is not intended to replace human pathologists but to augment their capabilities. Overall, the combination of AI technology with the expertise of pathologists can lead to improved diagnosis, better patient care, and more efficient workflows in digital pathology.
 

Eat as fast as you can whenever you can.

That was the med student mindset around food, as Catherine Harmon Toomer, MD, discovered during her school years. “Without a good system in place to counter that,” she explains, “unhealthy eating can get out of control, and that’s what happened to me.”

After med school, things got worse for Dr. Toomer. By her second year in practice as a family medicine physician, she’d gained a lot of weight and had been diagnosed with type 2 diabetes and cardiomyopathy. At 36, she went into congestive heart failure and was told she likely had 5 years to live.

A moment she described as “a huge wake-up call.”

Dr. Toomer is far from alone in her struggles to balance working in medicine and eating healthfully.

“Physicians face unique stresses because of the ubiquity of junk food in the clinical setting, easy use of food as a reward and stress reliever, and lack of time to create better wellness habits while counseling patients to do exactly that,” said John La Puma, MD, FACP, internist and cofounder of ChefMD and founder of Chef Clinic.

There is also the culture of medicine, which Dr. Toomer said looks down on self-care. “Even with break times, patient needs come before our own.” So, you sit down to eat, and there’s an emergency. Your clinic closes for lunch, but the phones still ring, and patients continue to email questions. Charting is also so time-consuming that “everything else gets put on the back burner.”

Sticking to a nutritious diet in this context can feel hopeless. But it isn’t. Really. Here are some doctor-tested, real-life ways you can nourish yourself while getting it all done.
 

Something Is Always Better Than Nothing

Sure, you might not be able to eat a balanced lunch or dinner while at work, conceded Amy Margulies, RD, LDN, owner of The Rebellious RD. But try to focus on the bigger picture and take small steps.

First, make sure you eat something, Ms. Margulies advised. “Skipping meals can lead to overeating later and negatively impact energy levels and concentration.”

Lisa Andrews, MEd, RD, LD, owner of Sound Bites Nutrition, recalled one of her patients, a gastrointestinal surgeon with reactive hypoglycemia and fatigue. “She was experiencing energy crashes mid-afternoon,” she said. It was only after starting to eat every 4-5 hours that her patient felt better.

Of course, this is easier said than done. “When you are running from one patient to the other and trying to keep on time with your schedule, there is very little time for eating and no time at all for cooking or even heating up food,” recalled Hélène Bertrand, MD, author of Low Back Pain: 3 Steps to Relief in 2 Minutes.

But during her 55 years as a family medicine physician, Dr. Bertrand found ways to improve (if not perfect) the situation. She lunched on nuts or seeds during the day or grabbed a 95% cacao chocolate bar — higher in antioxidants and lower in sugar than a candy bar.

If you don’t have time for breakfast, try drinking a complete protein shake while driving to work, Dr. Toomer recommended. “It’s not ideal, but it’s better than nothing.” Similarly, if the only way you’ll eat a high-protein, lower-carb snack like hummus is with potato chips, go for it, she said.

Basically, don’t be type A striving for perfection. Take good enough when you can and balance the rest when you have time.
 

Torpedo Temptation

From free treats in the break room to always-present pizza for residents, high-fat, high-sugar, low-nutrient fare is a constant temptation. “I worked with a physician who would bring a balanced lunch to work every day, then find whatever sweet was around for his afternoon treat,” recalled Ms. Margulies.“The cookies, cakes, and donuts were starting to add up — and stopping at one wasn’t working for him.”

What did work was Ms. Margulies’ suggestion to bring a single serving of dark chocolate and fruit to savor during a longer break. “Bringing your favorite treats in appropriate portions can help you stick with your plan throughout the day,” she explained, and you’ll have an easier time resisting what’s in the break room. “When you desire a treat, tell yourself you have what you need and don’t need to indulge in the ‘free food’ just because it’s there. You have power over your choices.”

How about tricking yourself into perceiving cherry tomatoes as treats? That might be unusual, but one of Dr. La Puma’s physician patients did just that, displaying the produce in a candy dish on his office counter. Not only did this strategy help remind him to snack healthfully, it also prompted his patients to ask about eating better, he said.
 

Preparation Is Still Underrated

Many people find meal prepping intimidating. But it doesn’t need to be complicated. For instance, try purchasing precut veggies, cooked chicken breasts, or other healthy convenience options. You can then combine them in packable containers to prep a few meals at a time. For less busy weeks, consider cooking the protein yourself and whipping up basic sauces (like pesto and vinaigrette) to jazz up your meals.

“I worked with a resident who was gaining weight each month,” recalled Ms. Margulies. “She would skip lunch, grab a random snack, then wait until she got home to eat anything she could find.”

Encouraged by Ms. Margulies, she prepared and portioned one or two balanced dinners each week, which she’d later reheat. She also bought fresh and dried fruit and high-protein snacks, keeping single servings in her car to eat on the way home.

Similarly, Jess DeGore, RD, LDN, CDCES, CHWC, a diabetes educator and owner of Dietitian Jess Nutrition, recalled an ob.gyn. client who constantly skipped meals and relied on vending machine snacks. To combat her resulting energy crashes, she followed Ms. DeGore’s advice to prep workday lunches (like quinoa salads) over the weekend and bring fruit and nut snacks to work.
 

Automate as Much as You Can

If healthy is already on hand, you’ll eat healthy, said Ms. Andrews. Build up a snack stash focusing on fiber and protein. Tote a lunch bag with a cooler pack if needed. Some suggestions:

• Oatmeal packets
• Individual Greek yogurt cups or drinkable yogurts
• Protein bars
• Protein shakes
• Fresh fruit
• Fresh veggie sticks
• Nuts, dried chickpeas, or edamame
• Trail mix
• Single servings of hummus, nut butter, or guacamole
• Dried seaweed snacks
• Whole grain crackers
• Hard-boiled eggs
• String cheese
• Peanut butter sandwich
• 95% cacao chocolate bar

Try a Meal Delivery Service

Meal delivery services can be pricey, but potentially worth the expense. By bringing meals or having them sent to your office, you won’t have to find time to go to the cafeteria and stand in line, noted Janese S. Laster, MD, an internal medicine, gastroenterology, obesity medicine, and nutrition physician and founder of Gut Theory Total Digestive Care. Instead, “you’ll have something to warm up and eat while writing notes or in between patients,” she said. Plus, “you won’t have an excuse to skip meals.”

Hydration Yes, Junk Drinks No

The following can be filed in the Doctors-Know-It-But-Don’t-Always-Do-It section: “Hunger can be mistaken for thirst,” said Ms. Margulies. “Staying hydrated will help you better assess whether you’re hungry or thirsty.” Choose water over soda or energy drinks, she added, to hydrate your body without unnecessary extra sugars, sugar substitutes, calories, caffeine, or sodium — all of which can affect how you feel.

Advocate for Your Health

Convincing your institution to make changes might be difficult or even impossible, but consider asking your workplace to implement initiatives like these to boost provider nutrition, suggested Jabe Brown, BHSc (Nat), founder of Melbourne Functional Medicine:

• Establish protected break times when doctors can step away from their duties to eat
• Add more nutritious cafeteria options, like salads, whole grains, and lean proteins
• Overhaul vending machine offerings
• Offer educational workshops on nutrition

Be Tenacious About Good Eating

For Dr. Toomer, that meant taking several years off from work to improve her health. After losing more than 100 pounds, she founded TOTAL Weight Care Institute to help other healthcare professionals follow in her footsteps.

For you, the path toward a healthier diet might be gradual — grabbing a more nutritious snack, spending an extra hour per week on food shopping or prep, remembering a water bottle. Whatever it looks like, make realistic lifestyle tweaks that work for you.

Maybe even try that apple-a-day thing.
 

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

Eat as fast as you can whenever you can.

That was the med student mindset around food, as Catherine Harmon Toomer, MD, discovered during her school years. “Without a good system in place to counter that,” she explains, “unhealthy eating can get out of control, and that’s what happened to me.”

After med school, things got worse for Dr. Toomer. By her second year in practice as a family medicine physician, she’d gained a lot of weight and had been diagnosed with type 2 diabetes and cardiomyopathy. At 36, she went into congestive heart failure and was told she likely had 5 years to live.

A moment she described as “a huge wake-up call.”

Dr. Toomer is far from alone in her struggles to balance working in medicine and eating healthfully.

“Physicians face unique stresses because of the ubiquity of junk food in the clinical setting, easy use of food as a reward and stress reliever, and lack of time to create better wellness habits while counseling patients to do exactly that,” said John La Puma, MD, FACP, internist and cofounder of ChefMD and founder of Chef Clinic.

There is also the culture of medicine, which Dr. Toomer said looks down on self-care. “Even with break times, patient needs come before our own.” So, you sit down to eat, and there’s an emergency. Your clinic closes for lunch, but the phones still ring, and patients continue to email questions. Charting is also so time-consuming that “everything else gets put on the back burner.”

Sticking to a nutritious diet in this context can feel hopeless. But it isn’t. Really. Here are some doctor-tested, real-life ways you can nourish yourself while getting it all done.
 

Something Is Always Better Than Nothing

Sure, you might not be able to eat a balanced lunch or dinner while at work, conceded Amy Margulies, RD, LDN, owner of The Rebellious RD. But try to focus on the bigger picture and take small steps.

First, make sure you eat something, Ms. Margulies advised. “Skipping meals can lead to overeating later and negatively impact energy levels and concentration.”

Lisa Andrews, MEd, RD, LD, owner of Sound Bites Nutrition, recalled one of her patients, a gastrointestinal surgeon with reactive hypoglycemia and fatigue. “She was experiencing energy crashes mid-afternoon,” she said. It was only after starting to eat every 4-5 hours that her patient felt better.

Of course, this is easier said than done. “When you are running from one patient to the other and trying to keep on time with your schedule, there is very little time for eating and no time at all for cooking or even heating up food,” recalled Hélène Bertrand, MD, author of Low Back Pain: 3 Steps to Relief in 2 Minutes.

But during her 55 years as a family medicine physician, Dr. Bertrand found ways to improve (if not perfect) the situation. She lunched on nuts or seeds during the day or grabbed a 95% cacao chocolate bar — higher in antioxidants and lower in sugar than a candy bar.

If you don’t have time for breakfast, try drinking a complete protein shake while driving to work, Dr. Toomer recommended. “It’s not ideal, but it’s better than nothing.” Similarly, if the only way you’ll eat a high-protein, lower-carb snack like hummus is with potato chips, go for it, she said.

Basically, don’t be type A striving for perfection. Take good enough when you can and balance the rest when you have time.
 

Torpedo Temptation

From free treats in the break room to always-present pizza for residents, high-fat, high-sugar, low-nutrient fare is a constant temptation. “I worked with a physician who would bring a balanced lunch to work every day, then find whatever sweet was around for his afternoon treat,” recalled Ms. Margulies.“The cookies, cakes, and donuts were starting to add up — and stopping at one wasn’t working for him.”

What did work was Ms. Margulies’ suggestion to bring a single serving of dark chocolate and fruit to savor during a longer break. “Bringing your favorite treats in appropriate portions can help you stick with your plan throughout the day,” she explained, and you’ll have an easier time resisting what’s in the break room. “When you desire a treat, tell yourself you have what you need and don’t need to indulge in the ‘free food’ just because it’s there. You have power over your choices.”

How about tricking yourself into perceiving cherry tomatoes as treats? That might be unusual, but one of Dr. La Puma’s physician patients did just that, displaying the produce in a candy dish on his office counter. Not only did this strategy help remind him to snack healthfully, it also prompted his patients to ask about eating better, he said.
 

Preparation Is Still Underrated

Many people find meal prepping intimidating. But it doesn’t need to be complicated. For instance, try purchasing precut veggies, cooked chicken breasts, or other healthy convenience options. You can then combine them in packable containers to prep a few meals at a time. For less busy weeks, consider cooking the protein yourself and whipping up basic sauces (like pesto and vinaigrette) to jazz up your meals.

“I worked with a resident who was gaining weight each month,” recalled Ms. Margulies. “She would skip lunch, grab a random snack, then wait until she got home to eat anything she could find.”

Encouraged by Ms. Margulies, she prepared and portioned one or two balanced dinners each week, which she’d later reheat. She also bought fresh and dried fruit and high-protein snacks, keeping single servings in her car to eat on the way home.

Similarly, Jess DeGore, RD, LDN, CDCES, CHWC, a diabetes educator and owner of Dietitian Jess Nutrition, recalled an ob.gyn. client who constantly skipped meals and relied on vending machine snacks. To combat her resulting energy crashes, she followed Ms. DeGore’s advice to prep workday lunches (like quinoa salads) over the weekend and bring fruit and nut snacks to work.
 

Automate as Much as You Can

If healthy is already on hand, you’ll eat healthy, said Ms. Andrews. Build up a snack stash focusing on fiber and protein. Tote a lunch bag with a cooler pack if needed. Some suggestions:

• Oatmeal packets
• Individual Greek yogurt cups or drinkable yogurts
• Protein bars
• Protein shakes
• Fresh fruit
• Fresh veggie sticks
• Nuts, dried chickpeas, or edamame
• Trail mix
• Single servings of hummus, nut butter, or guacamole
• Dried seaweed snacks
• Whole grain crackers
• Hard-boiled eggs
• String cheese
• Peanut butter sandwich
• 95% cacao chocolate bar

Try a Meal Delivery Service

Meal delivery services can be pricey, but potentially worth the expense. By bringing meals or having them sent to your office, you won’t have to find time to go to the cafeteria and stand in line, noted Janese S. Laster, MD, an internal medicine, gastroenterology, obesity medicine, and nutrition physician and founder of Gut Theory Total Digestive Care. Instead, “you’ll have something to warm up and eat while writing notes or in between patients,” she said. Plus, “you won’t have an excuse to skip meals.”

Hydration Yes, Junk Drinks No

The following can be filed in the Doctors-Know-It-But-Don’t-Always-Do-It section: “Hunger can be mistaken for thirst,” said Ms. Margulies. “Staying hydrated will help you better assess whether you’re hungry or thirsty.” Choose water over soda or energy drinks, she added, to hydrate your body without unnecessary extra sugars, sugar substitutes, calories, caffeine, or sodium — all of which can affect how you feel.

Advocate for Your Health

Convincing your institution to make changes might be difficult or even impossible, but consider asking your workplace to implement initiatives like these to boost provider nutrition, suggested Jabe Brown, BHSc (Nat), founder of Melbourne Functional Medicine:

• Establish protected break times when doctors can step away from their duties to eat
• Add more nutritious cafeteria options, like salads, whole grains, and lean proteins
• Overhaul vending machine offerings
• Offer educational workshops on nutrition

Be Tenacious About Good Eating

For Dr. Toomer, that meant taking several years off from work to improve her health. After losing more than 100 pounds, she founded TOTAL Weight Care Institute to help other healthcare professionals follow in her footsteps.

For you, the path toward a healthier diet might be gradual — grabbing a more nutritious snack, spending an extra hour per week on food shopping or prep, remembering a water bottle. Whatever it looks like, make realistic lifestyle tweaks that work for you.

Maybe even try that apple-a-day thing.
 

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

Eat as fast as you can whenever you can.

That was the med student mindset around food, as Catherine Harmon Toomer, MD, discovered during her school years. “Without a good system in place to counter that,” she explains, “unhealthy eating can get out of control, and that’s what happened to me.”

After med school, things got worse for Dr. Toomer. By her second year in practice as a family medicine physician, she’d gained a lot of weight and had been diagnosed with type 2 diabetes and cardiomyopathy. At 36, she went into congestive heart failure and was told she likely had 5 years to live.

A moment she described as “a huge wake-up call.”

Dr. Toomer is far from alone in her struggles to balance working in medicine and eating healthfully.

“Physicians face unique stresses because of the ubiquity of junk food in the clinical setting, easy use of food as a reward and stress reliever, and lack of time to create better wellness habits while counseling patients to do exactly that,” said John La Puma, MD, FACP, internist and cofounder of ChefMD and founder of Chef Clinic.

There is also the culture of medicine, which Dr. Toomer said looks down on self-care. “Even with break times, patient needs come before our own.” So, you sit down to eat, and there’s an emergency. Your clinic closes for lunch, but the phones still ring, and patients continue to email questions. Charting is also so time-consuming that “everything else gets put on the back burner.”

Sticking to a nutritious diet in this context can feel hopeless. But it isn’t. Really. Here are some doctor-tested, real-life ways you can nourish yourself while getting it all done.
 

Something Is Always Better Than Nothing

Sure, you might not be able to eat a balanced lunch or dinner while at work, conceded Amy Margulies, RD, LDN, owner of The Rebellious RD. But try to focus on the bigger picture and take small steps.

First, make sure you eat something, Ms. Margulies advised. “Skipping meals can lead to overeating later and negatively impact energy levels and concentration.”

Lisa Andrews, MEd, RD, LD, owner of Sound Bites Nutrition, recalled one of her patients, a gastrointestinal surgeon with reactive hypoglycemia and fatigue. “She was experiencing energy crashes mid-afternoon,” she said. It was only after starting to eat every 4-5 hours that her patient felt better.

Of course, this is easier said than done. “When you are running from one patient to the other and trying to keep on time with your schedule, there is very little time for eating and no time at all for cooking or even heating up food,” recalled Hélène Bertrand, MD, author of Low Back Pain: 3 Steps to Relief in 2 Minutes.

But during her 55 years as a family medicine physician, Dr. Bertrand found ways to improve (if not perfect) the situation. She lunched on nuts or seeds during the day or grabbed a 95% cacao chocolate bar — higher in antioxidants and lower in sugar than a candy bar.

If you don’t have time for breakfast, try drinking a complete protein shake while driving to work, Dr. Toomer recommended. “It’s not ideal, but it’s better than nothing.” Similarly, if the only way you’ll eat a high-protein, lower-carb snack like hummus is with potato chips, go for it, she said.

Basically, don’t be type A striving for perfection. Take good enough when you can and balance the rest when you have time.
 

Torpedo Temptation

From free treats in the break room to always-present pizza for residents, high-fat, high-sugar, low-nutrient fare is a constant temptation. “I worked with a physician who would bring a balanced lunch to work every day, then find whatever sweet was around for his afternoon treat,” recalled Ms. Margulies.“The cookies, cakes, and donuts were starting to add up — and stopping at one wasn’t working for him.”

What did work was Ms. Margulies’ suggestion to bring a single serving of dark chocolate and fruit to savor during a longer break. “Bringing your favorite treats in appropriate portions can help you stick with your plan throughout the day,” she explained, and you’ll have an easier time resisting what’s in the break room. “When you desire a treat, tell yourself you have what you need and don’t need to indulge in the ‘free food’ just because it’s there. You have power over your choices.”

How about tricking yourself into perceiving cherry tomatoes as treats? That might be unusual, but one of Dr. La Puma’s physician patients did just that, displaying the produce in a candy dish on his office counter. Not only did this strategy help remind him to snack healthfully, it also prompted his patients to ask about eating better, he said.
 

Preparation Is Still Underrated

Many people find meal prepping intimidating. But it doesn’t need to be complicated. For instance, try purchasing precut veggies, cooked chicken breasts, or other healthy convenience options. You can then combine them in packable containers to prep a few meals at a time. For less busy weeks, consider cooking the protein yourself and whipping up basic sauces (like pesto and vinaigrette) to jazz up your meals.

“I worked with a resident who was gaining weight each month,” recalled Ms. Margulies. “She would skip lunch, grab a random snack, then wait until she got home to eat anything she could find.”

Encouraged by Ms. Margulies, she prepared and portioned one or two balanced dinners each week, which she’d later reheat. She also bought fresh and dried fruit and high-protein snacks, keeping single servings in her car to eat on the way home.

Similarly, Jess DeGore, RD, LDN, CDCES, CHWC, a diabetes educator and owner of Dietitian Jess Nutrition, recalled an ob.gyn. client who constantly skipped meals and relied on vending machine snacks. To combat her resulting energy crashes, she followed Ms. DeGore’s advice to prep workday lunches (like quinoa salads) over the weekend and bring fruit and nut snacks to work.
 

Automate as Much as You Can

If healthy is already on hand, you’ll eat healthy, said Ms. Andrews. Build up a snack stash focusing on fiber and protein. Tote a lunch bag with a cooler pack if needed. Some suggestions:

• Oatmeal packets
• Individual Greek yogurt cups or drinkable yogurts
• Protein bars
• Protein shakes
• Fresh fruit
• Fresh veggie sticks
• Nuts, dried chickpeas, or edamame
• Trail mix
• Single servings of hummus, nut butter, or guacamole
• Dried seaweed snacks
• Whole grain crackers
• Hard-boiled eggs
• String cheese
• Peanut butter sandwich
• 95% cacao chocolate bar

Try a Meal Delivery Service

Meal delivery services can be pricey, but potentially worth the expense. By bringing meals or having them sent to your office, you won’t have to find time to go to the cafeteria and stand in line, noted Janese S. Laster, MD, an internal medicine, gastroenterology, obesity medicine, and nutrition physician and founder of Gut Theory Total Digestive Care. Instead, “you’ll have something to warm up and eat while writing notes or in between patients,” she said. Plus, “you won’t have an excuse to skip meals.”

Hydration Yes, Junk Drinks No

The following can be filed in the Doctors-Know-It-But-Don’t-Always-Do-It section: “Hunger can be mistaken for thirst,” said Ms. Margulies. “Staying hydrated will help you better assess whether you’re hungry or thirsty.” Choose water over soda or energy drinks, she added, to hydrate your body without unnecessary extra sugars, sugar substitutes, calories, caffeine, or sodium — all of which can affect how you feel.

Advocate for Your Health

Convincing your institution to make changes might be difficult or even impossible, but consider asking your workplace to implement initiatives like these to boost provider nutrition, suggested Jabe Brown, BHSc (Nat), founder of Melbourne Functional Medicine:

• Establish protected break times when doctors can step away from their duties to eat
• Add more nutritious cafeteria options, like salads, whole grains, and lean proteins
• Overhaul vending machine offerings
• Offer educational workshops on nutrition

Be Tenacious About Good Eating

For Dr. Toomer, that meant taking several years off from work to improve her health. After losing more than 100 pounds, she founded TOTAL Weight Care Institute to help other healthcare professionals follow in her footsteps.

For you, the path toward a healthier diet might be gradual — grabbing a more nutritious snack, spending an extra hour per week on food shopping or prep, remembering a water bottle. Whatever it looks like, make realistic lifestyle tweaks that work for you.

Maybe even try that apple-a-day thing.
 

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

Paxlovid, an antiviral approved in 2023 to treat acute infections of COVID-19, is showing great potential as a new treatment for long COVID and may be the most promising experimental therapy now being studied for treating the condition.

New research offers strong evidence that Paxlovid provides significant benefits for COVID-19 patients who are at high risk for severe or prolonged disease, particularly older adults and those who are immunocompromised, said Lisa Sanders, MD, medical director of Yale’s Long COVID Multidisciplinary Care Center, New Haven, Connecticut. 

“We all know that long COVID is a disease smorgasbord of illnesses that have been somehow triggered by COVID. So, the question is, are there some types of these disorders that can respond to Paxlovid?” Dr. Sanders said. 

Some patients have also benefited from supplements such as N-acetyl cysteine (NAC), as well as vitamins B, C, D and alpha lipoic acid, in which the risks are low and there are potential benefits, Dr. Sanders said.

As researchers continue to study new treatments for long COVID, for which there are no standard approved therapies, Dr. Sanders suggested doctors might turn to Paxlovid and other promising therapeutics that have shown benefits in preliminary study findings.

A study published in 2023 by JAMA Internal Medicine reviewed the charts of nearly 300,000 veterans with severe acute COVID infections. The study found that Paxlovid treatment reduced the likelihood of developing long COVID. But a more recent study at Stanford University, Palo Alto, California — the STOP-PASC trial— did not find Paxlovid improved symptoms when given to 155 patients who had already recovered from acute infection. Participants with long COVID symptoms — and who had on average recovered from acute infection around 16 months earlier — were given a 15-day course of Paxlovid. Common symptoms like fog, fatigue, and cardiovascular or gastrointestinal symptoms did not improve.

However, long COVID likely has multiple drivers. Viral persistence may still be at play for a subset of patients. This means that, despite the fact that patients recover from acute infection, hidden reservoirs of SARS-CoV-2 are still present in the body, possibly bringing on long COVID symptoms. Which means Paxlovid may help some long COVID patients but not others, Dr. Sanders explained. That’s why research needs to continue to identify the best cases for Paxlovid’s use and to identify other treatments for those who do not benefit from Paxlovid.

The PAX LC trial at Yale suggests there may not be a one-size-fits-all treatment for the condition, but a range of factors that may determine the best therapy for individual patients. Led by Yale School of Medicine’s Harlan Krumholz, MD, and Akiko Iwasaki, PhD, the study tested the effects of Paxlovid overall and was designed to determine who is most likely to benefit from antiviral treatment and gain further understanding of the immune response in long COVID. Results should be reported soon. 

“This acknowledges one line of thinking that long COVID is caused by viral persistence,” Dr. Sanders said. “Do these people have hidden reservoirs of the virus? The question is, are there people who seem to respond [to Paxlovid]? And if so, what characterizes these people?”
 

Low-Risk, High-Reward Supplements

Some of Dr. Sanders’ colleagues at Yale are focusing on long COVID’s neurological symptoms and neuropathogenesis. There’s evidence showing these symptoms — notably brain fog — can be treated with supplements. 

In 2022, a Yale study by Arman Fesharaki-Zadeh, MD, PhD, found promise in treating brain fog through a combination supplement of NAC and guanfacine — the latter developed by Yale neuroscientist, Amy Arnsten, PhD. 

The two published their study in Neuroimmunology Reports in November 2023. NAC is available over the counter and patients can get a prescription for guanfacine off label from their physician. Guanfacine is approved to treat high blood pressure by decreasing heart rate and relaxing blood vessels. But it’s also been shown to treat attention-deficit/hyperactivity disorder (ADHD) and other cognitive issues. 

Though NAC can treat respiratory problems, it’s also commonly used to treat postconcussion symptoms. Dr. Fesharaki-Zadeh found that it helps treat brain fog, increases energy, and improves memory. When paired with guanfacine, substantial benefits were reported, such as better multitasking abilities and markedly improved organizational skills. 

Dr. Sanders is now using NAC and guanfacine for patients in her clinic. 
 

‘Mitochondrial Enhancement’ Through Vitamins

Dr. Sanders has also used a combination of alpha lipoic acid and vitamin C, and a combo of B vitamins that make up what’s called a “mitochondrial enhancement regimen.”

To treat a very common symptom like fatigue, Dr. Sanders prefers supplement combinations over other drugs like Modafinil or Adderall. 

Modafinil is a central nervous system stimulant used to reduce extreme sleepiness caused by narcolepsy or other sleep disorders. Adderall is an amphetamine also used to treat narcolepsy as well as ADHD. Both work on your sleep and alertness, but long COVID affects the whole body, causing a physical fatigue similar to postexertional malaise (PEM) that isn’t remedied by those kinds of drugs, as studies suggest what’s involved in PEM is mitochondria, Dr. Sanders said. 

PEM is a worsening of symptoms that occurs after minimal physical or mental exertion. These are activities that should be well tolerated, but PEM causes extreme fatigue and flu-like symptoms. It’s become a hallmark symptom of long COVID after having already been a key diagnostic factor in myalgic encephalomyelitis/chronic fatigue syndrome.

As Dr. Sanders noted in her long COVID blog, which tracks the latest research and treatment options for doctors who treat long COVID patients, previous studies have shown low vitamin D levels may not only increase the risk for severe COVID-19 but delay recovery from long COVID. Those without long COVID had higher levels of vitamin D, compared with long COVID patients. Vitamin D is known to boost the immune system.

Dr. Sanders found that those with vitamin D deficiencies are most likely to benefit from this approach. For people who don’t have sufficient sun exposure, which prompts the production of vitamin D, she says supplementation with 1000 IUs of vitamin D3 daily is enough for most adults.

Research is also currently being underway on the use of the diabetes drug metformin in people with acute COVID infections to determine if it may reduce the likelihood of developing long COVID. In a recent long COVID clinical trial, early outpatient COVID-19 treatment with metformin decreased the subsequent risk for long COVID by 41.3% during 10-month follow-up. 
 

Other New Treatments Under Study

Dr. Sanders believes the foundation for many of long COVID’s symptoms could be neurological. 

“I think that long COVID is probably a neurologic disorder,” Dr. Sanders said. 

Lindsey McAlpine, MD, director of the Yale Medicine NeuroCovid Clinic, is focusing on neuropsychiatric long COVID and the causes of neurologic post-acute sequelae of SARS-CoV-2 infection (neuro-PASC). Symptoms of neuro-PASC include cognitive impairment, headaches, and dizziness.

“Lindsey is trying to see which parts of the brain are involved and see if there are phenotypes of brain abnormalities that match up with clinical abnormalities,” Dr. Sanders said.

The National Institute of Neurological Disorders and Stroke recently awarded her a 5-year K23 grant to support her ongoing study, “Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”

Utilizing advanced MRI techniques to identify microvascular dysfunction biomarkers in the brain, Dr. McAlpine hopes to unearth and better understand the pathophysiology behind neurological issues post COVID.

Many of Dr. McAlpine’s patients with cognitive symptoms have responded well to NAC and guanfacine. 

Still, the hope is that her brain-imaging studies will bear fruit that leads to a better understanding of long COVID and new treatment methods.

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

Paxlovid, an antiviral approved in 2023 to treat acute infections of COVID-19, is showing great potential as a new treatment for long COVID and may be the most promising experimental therapy now being studied for treating the condition.

New research offers strong evidence that Paxlovid provides significant benefits for COVID-19 patients who are at high risk for severe or prolonged disease, particularly older adults and those who are immunocompromised, said Lisa Sanders, MD, medical director of Yale’s Long COVID Multidisciplinary Care Center, New Haven, Connecticut. 

“We all know that long COVID is a disease smorgasbord of illnesses that have been somehow triggered by COVID. So, the question is, are there some types of these disorders that can respond to Paxlovid?” Dr. Sanders said. 

Some patients have also benefited from supplements such as N-acetyl cysteine (NAC), as well as vitamins B, C, D and alpha lipoic acid, in which the risks are low and there are potential benefits, Dr. Sanders said.

As researchers continue to study new treatments for long COVID, for which there are no standard approved therapies, Dr. Sanders suggested doctors might turn to Paxlovid and other promising therapeutics that have shown benefits in preliminary study findings.

A study published in 2023 by JAMA Internal Medicine reviewed the charts of nearly 300,000 veterans with severe acute COVID infections. The study found that Paxlovid treatment reduced the likelihood of developing long COVID. But a more recent study at Stanford University, Palo Alto, California — the STOP-PASC trial— did not find Paxlovid improved symptoms when given to 155 patients who had already recovered from acute infection. Participants with long COVID symptoms — and who had on average recovered from acute infection around 16 months earlier — were given a 15-day course of Paxlovid. Common symptoms like fog, fatigue, and cardiovascular or gastrointestinal symptoms did not improve.

However, long COVID likely has multiple drivers. Viral persistence may still be at play for a subset of patients. This means that, despite the fact that patients recover from acute infection, hidden reservoirs of SARS-CoV-2 are still present in the body, possibly bringing on long COVID symptoms. Which means Paxlovid may help some long COVID patients but not others, Dr. Sanders explained. That’s why research needs to continue to identify the best cases for Paxlovid’s use and to identify other treatments for those who do not benefit from Paxlovid.

The PAX LC trial at Yale suggests there may not be a one-size-fits-all treatment for the condition, but a range of factors that may determine the best therapy for individual patients. Led by Yale School of Medicine’s Harlan Krumholz, MD, and Akiko Iwasaki, PhD, the study tested the effects of Paxlovid overall and was designed to determine who is most likely to benefit from antiviral treatment and gain further understanding of the immune response in long COVID. Results should be reported soon. 

“This acknowledges one line of thinking that long COVID is caused by viral persistence,” Dr. Sanders said. “Do these people have hidden reservoirs of the virus? The question is, are there people who seem to respond [to Paxlovid]? And if so, what characterizes these people?”
 

Low-Risk, High-Reward Supplements

Some of Dr. Sanders’ colleagues at Yale are focusing on long COVID’s neurological symptoms and neuropathogenesis. There’s evidence showing these symptoms — notably brain fog — can be treated with supplements. 

In 2022, a Yale study by Arman Fesharaki-Zadeh, MD, PhD, found promise in treating brain fog through a combination supplement of NAC and guanfacine — the latter developed by Yale neuroscientist, Amy Arnsten, PhD. 

The two published their study in Neuroimmunology Reports in November 2023. NAC is available over the counter and patients can get a prescription for guanfacine off label from their physician. Guanfacine is approved to treat high blood pressure by decreasing heart rate and relaxing blood vessels. But it’s also been shown to treat attention-deficit/hyperactivity disorder (ADHD) and other cognitive issues. 

Though NAC can treat respiratory problems, it’s also commonly used to treat postconcussion symptoms. Dr. Fesharaki-Zadeh found that it helps treat brain fog, increases energy, and improves memory. When paired with guanfacine, substantial benefits were reported, such as better multitasking abilities and markedly improved organizational skills. 

Dr. Sanders is now using NAC and guanfacine for patients in her clinic. 
 

‘Mitochondrial Enhancement’ Through Vitamins

Dr. Sanders has also used a combination of alpha lipoic acid and vitamin C, and a combo of B vitamins that make up what’s called a “mitochondrial enhancement regimen.”

To treat a very common symptom like fatigue, Dr. Sanders prefers supplement combinations over other drugs like Modafinil or Adderall. 

Modafinil is a central nervous system stimulant used to reduce extreme sleepiness caused by narcolepsy or other sleep disorders. Adderall is an amphetamine also used to treat narcolepsy as well as ADHD. Both work on your sleep and alertness, but long COVID affects the whole body, causing a physical fatigue similar to postexertional malaise (PEM) that isn’t remedied by those kinds of drugs, as studies suggest what’s involved in PEM is mitochondria, Dr. Sanders said. 

PEM is a worsening of symptoms that occurs after minimal physical or mental exertion. These are activities that should be well tolerated, but PEM causes extreme fatigue and flu-like symptoms. It’s become a hallmark symptom of long COVID after having already been a key diagnostic factor in myalgic encephalomyelitis/chronic fatigue syndrome.

As Dr. Sanders noted in her long COVID blog, which tracks the latest research and treatment options for doctors who treat long COVID patients, previous studies have shown low vitamin D levels may not only increase the risk for severe COVID-19 but delay recovery from long COVID. Those without long COVID had higher levels of vitamin D, compared with long COVID patients. Vitamin D is known to boost the immune system.

Dr. Sanders found that those with vitamin D deficiencies are most likely to benefit from this approach. For people who don’t have sufficient sun exposure, which prompts the production of vitamin D, she says supplementation with 1000 IUs of vitamin D3 daily is enough for most adults.

Research is also currently being underway on the use of the diabetes drug metformin in people with acute COVID infections to determine if it may reduce the likelihood of developing long COVID. In a recent long COVID clinical trial, early outpatient COVID-19 treatment with metformin decreased the subsequent risk for long COVID by 41.3% during 10-month follow-up. 
 

Other New Treatments Under Study

Dr. Sanders believes the foundation for many of long COVID’s symptoms could be neurological. 

“I think that long COVID is probably a neurologic disorder,” Dr. Sanders said. 

Lindsey McAlpine, MD, director of the Yale Medicine NeuroCovid Clinic, is focusing on neuropsychiatric long COVID and the causes of neurologic post-acute sequelae of SARS-CoV-2 infection (neuro-PASC). Symptoms of neuro-PASC include cognitive impairment, headaches, and dizziness.

“Lindsey is trying to see which parts of the brain are involved and see if there are phenotypes of brain abnormalities that match up with clinical abnormalities,” Dr. Sanders said.

The National Institute of Neurological Disorders and Stroke recently awarded her a 5-year K23 grant to support her ongoing study, “Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”

Utilizing advanced MRI techniques to identify microvascular dysfunction biomarkers in the brain, Dr. McAlpine hopes to unearth and better understand the pathophysiology behind neurological issues post COVID.

Many of Dr. McAlpine’s patients with cognitive symptoms have responded well to NAC and guanfacine. 

Still, the hope is that her brain-imaging studies will bear fruit that leads to a better understanding of long COVID and new treatment methods.

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

Paxlovid, an antiviral approved in 2023 to treat acute infections of COVID-19, is showing great potential as a new treatment for long COVID and may be the most promising experimental therapy now being studied for treating the condition.

New research offers strong evidence that Paxlovid provides significant benefits for COVID-19 patients who are at high risk for severe or prolonged disease, particularly older adults and those who are immunocompromised, said Lisa Sanders, MD, medical director of Yale’s Long COVID Multidisciplinary Care Center, New Haven, Connecticut. 

“We all know that long COVID is a disease smorgasbord of illnesses that have been somehow triggered by COVID. So, the question is, are there some types of these disorders that can respond to Paxlovid?” Dr. Sanders said. 

Some patients have also benefited from supplements such as N-acetyl cysteine (NAC), as well as vitamins B, C, D and alpha lipoic acid, in which the risks are low and there are potential benefits, Dr. Sanders said.

As researchers continue to study new treatments for long COVID, for which there are no standard approved therapies, Dr. Sanders suggested doctors might turn to Paxlovid and other promising therapeutics that have shown benefits in preliminary study findings.

A study published in 2023 by JAMA Internal Medicine reviewed the charts of nearly 300,000 veterans with severe acute COVID infections. The study found that Paxlovid treatment reduced the likelihood of developing long COVID. But a more recent study at Stanford University, Palo Alto, California — the STOP-PASC trial— did not find Paxlovid improved symptoms when given to 155 patients who had already recovered from acute infection. Participants with long COVID symptoms — and who had on average recovered from acute infection around 16 months earlier — were given a 15-day course of Paxlovid. Common symptoms like fog, fatigue, and cardiovascular or gastrointestinal symptoms did not improve.

However, long COVID likely has multiple drivers. Viral persistence may still be at play for a subset of patients. This means that, despite the fact that patients recover from acute infection, hidden reservoirs of SARS-CoV-2 are still present in the body, possibly bringing on long COVID symptoms. Which means Paxlovid may help some long COVID patients but not others, Dr. Sanders explained. That’s why research needs to continue to identify the best cases for Paxlovid’s use and to identify other treatments for those who do not benefit from Paxlovid.

The PAX LC trial at Yale suggests there may not be a one-size-fits-all treatment for the condition, but a range of factors that may determine the best therapy for individual patients. Led by Yale School of Medicine’s Harlan Krumholz, MD, and Akiko Iwasaki, PhD, the study tested the effects of Paxlovid overall and was designed to determine who is most likely to benefit from antiviral treatment and gain further understanding of the immune response in long COVID. Results should be reported soon. 

“This acknowledges one line of thinking that long COVID is caused by viral persistence,” Dr. Sanders said. “Do these people have hidden reservoirs of the virus? The question is, are there people who seem to respond [to Paxlovid]? And if so, what characterizes these people?”
 

Low-Risk, High-Reward Supplements

Some of Dr. Sanders’ colleagues at Yale are focusing on long COVID’s neurological symptoms and neuropathogenesis. There’s evidence showing these symptoms — notably brain fog — can be treated with supplements. 

In 2022, a Yale study by Arman Fesharaki-Zadeh, MD, PhD, found promise in treating brain fog through a combination supplement of NAC and guanfacine — the latter developed by Yale neuroscientist, Amy Arnsten, PhD. 

The two published their study in Neuroimmunology Reports in November 2023. NAC is available over the counter and patients can get a prescription for guanfacine off label from their physician. Guanfacine is approved to treat high blood pressure by decreasing heart rate and relaxing blood vessels. But it’s also been shown to treat attention-deficit/hyperactivity disorder (ADHD) and other cognitive issues. 

Though NAC can treat respiratory problems, it’s also commonly used to treat postconcussion symptoms. Dr. Fesharaki-Zadeh found that it helps treat brain fog, increases energy, and improves memory. When paired with guanfacine, substantial benefits were reported, such as better multitasking abilities and markedly improved organizational skills. 

Dr. Sanders is now using NAC and guanfacine for patients in her clinic. 
 

‘Mitochondrial Enhancement’ Through Vitamins

Dr. Sanders has also used a combination of alpha lipoic acid and vitamin C, and a combo of B vitamins that make up what’s called a “mitochondrial enhancement regimen.”

To treat a very common symptom like fatigue, Dr. Sanders prefers supplement combinations over other drugs like Modafinil or Adderall. 

Modafinil is a central nervous system stimulant used to reduce extreme sleepiness caused by narcolepsy or other sleep disorders. Adderall is an amphetamine also used to treat narcolepsy as well as ADHD. Both work on your sleep and alertness, but long COVID affects the whole body, causing a physical fatigue similar to postexertional malaise (PEM) that isn’t remedied by those kinds of drugs, as studies suggest what’s involved in PEM is mitochondria, Dr. Sanders said. 

PEM is a worsening of symptoms that occurs after minimal physical or mental exertion. These are activities that should be well tolerated, but PEM causes extreme fatigue and flu-like symptoms. It’s become a hallmark symptom of long COVID after having already been a key diagnostic factor in myalgic encephalomyelitis/chronic fatigue syndrome.

As Dr. Sanders noted in her long COVID blog, which tracks the latest research and treatment options for doctors who treat long COVID patients, previous studies have shown low vitamin D levels may not only increase the risk for severe COVID-19 but delay recovery from long COVID. Those without long COVID had higher levels of vitamin D, compared with long COVID patients. Vitamin D is known to boost the immune system.

Dr. Sanders found that those with vitamin D deficiencies are most likely to benefit from this approach. For people who don’t have sufficient sun exposure, which prompts the production of vitamin D, she says supplementation with 1000 IUs of vitamin D3 daily is enough for most adults.

Research is also currently being underway on the use of the diabetes drug metformin in people with acute COVID infections to determine if it may reduce the likelihood of developing long COVID. In a recent long COVID clinical trial, early outpatient COVID-19 treatment with metformin decreased the subsequent risk for long COVID by 41.3% during 10-month follow-up. 
 

Other New Treatments Under Study

Dr. Sanders believes the foundation for many of long COVID’s symptoms could be neurological. 

“I think that long COVID is probably a neurologic disorder,” Dr. Sanders said. 

Lindsey McAlpine, MD, director of the Yale Medicine NeuroCovid Clinic, is focusing on neuropsychiatric long COVID and the causes of neurologic post-acute sequelae of SARS-CoV-2 infection (neuro-PASC). Symptoms of neuro-PASC include cognitive impairment, headaches, and dizziness.

“Lindsey is trying to see which parts of the brain are involved and see if there are phenotypes of brain abnormalities that match up with clinical abnormalities,” Dr. Sanders said.

The National Institute of Neurological Disorders and Stroke recently awarded her a 5-year K23 grant to support her ongoing study, “Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”

Utilizing advanced MRI techniques to identify microvascular dysfunction biomarkers in the brain, Dr. McAlpine hopes to unearth and better understand the pathophysiology behind neurological issues post COVID.

Many of Dr. McAlpine’s patients with cognitive symptoms have responded well to NAC and guanfacine. 

Still, the hope is that her brain-imaging studies will bear fruit that leads to a better understanding of long COVID and new treatment methods.

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

The escalating costs of medications and the prevalence of medical bankruptcy in our country have drawn criticism from governments, regulators, and the media. Federal and state governments are exploring various strategies to mitigate this issue, including the Inflation Reduction Act (IRA) for drug price negotiations and the establishment of state Pharmaceutical Drug Affordability Boards (PDABs). However, it’s uncertain whether these measures will effectively reduce patients’ medication expenses, given the tendency of pharmacy benefit managers (PBMs) to favor more expensive drugs on their formularies and the implementation challenges faced by PDABs.

The question then arises: How can we promptly assist patients, especially those with multiple chronic conditions, in affording their healthcare? Many of these patients are enrolled in high-deductible plans and struggle to cover all their medical and pharmacy costs.

A significant obstacle to healthcare affordability emerged in 2018 with the introduction of Copay Accumulator Programs by PBMs. These programs prevent patients from applying manufacturer copay cards toward their deductible and maximum out-of-pocket (OOP) costs. The impact of these policies has been devastating, leading to decreased adherence to medications and delayed necessary medical procedures, such as colonoscopies. Copay accumulators do nothing to address the high cost of medical care. They merely shift the burden from insurance companies to patients.

There is a direct solution to help patients, particularly those burdened with high pharmacy bills, afford their medical care. It would be that all payments from patients, including manufacturer copay cards, count toward their deductible and maximum OOP costs. This should apply regardless of whether the insurance plan is fully funded or a self-insured employer plan. This would be an immediate step toward making healthcare more affordable for patients.
 

Copay Accumulator Programs

How did these detrimental policies, which have been proven to harm patients, originate? It’s interesting that health insurance policies for federal employees do not allow these programs and yet the federal government has done little to protect its citizens from these egregious policies. More on that later.

In 2018, insurance companies and PBMs conceived an idea to introduce what they called copay accumulator adjustment programs. These programs would prevent the use of manufacturer copay cards from counting toward patient deductibles or OOP maximums. They justified this by arguing that manufacturer copay cards encouraged patients to opt for higher-priced brand drugs when lower-cost generics were available.

However, data from IQVIA contradicts this claim. An analysis of copay card usage from 2013 to 2017 revealed that a mere 0.4% of these cards were used for brand-name drugs that had already lost their exclusivity. This indicates that the vast majority of copay cards were not being used to purchase more expensive brand-name drugs when cheaper, generic alternatives were available.

Another argument put forth by one of the large PBMs was that patients with high deductibles don’t have enough “skin in the game” due to their low premiums, and therefore don’t deserve to have their deductible covered by a copay card. This raises the question, “Does a patient with hemophilia or systemic lupus who can’t afford a low deductible plan not have ‘skin in the game’? Is that a fair assessment?” It’s disconcerting to see a multibillion-dollar company dictating who deserves to have their deductible covered. These policies clearly disproportionately harm patients with chronic illnesses, especially those with high deductibles. As a result, many organizations have labeled these policies as discriminatory.

Following the implementation of accumulator programs in 2018 and 2019, many patients were unaware that their copay cards weren’t contributing toward their deductibles. They were taken aback when specialty pharmacies informed them of owing substantial amounts because of unmet deductibles. Consequently, patients discontinued their medications, leading to disease progression and increased costs. The only downside for health insurers and PBMs was the negative publicity associated with patients losing medication access.
 

Maximizer Programs

By the end of 2019, the three major PBMs had devised a strategy to keep patients on their medication throughout the year, without counting copay cards toward the deductible, and found a way to profit more from these cards, sometimes quadrupling their value. This was the birth of the maximizer programs.

Maximizers exploit a “loophole” in the Affordable Care Act (ACA). The ACA defines Essential Healthcare Benefits (EHB); anything not listed as an EHB is deemed “non-essential.” As a result, neither personal payments nor copay cards count toward deductibles or OOP maximums. Patients were informed that neither their own money nor manufacturer copay cards would count toward their deductible/OOP max.

One of my patients was warned that without enrolling in the maximizer program through SaveOnSP (owned by Express Scripts), she would bear the full cost of the drug, and nothing would count toward her OOP max. Frightened, she enrolled and surrendered her manufacturer copay card to SaveOnSP. Maximizers pocket the maximum value of the copay card, even if it exceeds the insurance plan’s yearly cost share by threefold or more. To do this legally, PBMs increase the patient’s original cost share amount during the plan year to match the value of the manufacturer copay card.
 

Combating These Programs

Nineteen states, the District of Columbia, and Puerto Rico have outlawed copay accumulators in health plans under state jurisdiction. I personally testified in Louisiana, leading to a ban in our state. CSRO’s award-winning map tool can show if your state has passed the ban on copay accumulator programs. However, many states have not passed bans on copay accumulators and self-insured employer groups, which fall under the Department of Labor and not state regulation, are still unaffected. There is also proposed federal legislation, the “Help Ensure Lower Patient Copays Act,” that would prohibit the use of copay accumulators in exchange plans. Despite having bipartisan support, it is having a hard time getting across the finish line in Congress.

In 2020, the Department of Health and Human Services (HHS) issued a rule prohibiting accumulator programs in all plans if the product was a brand name without a generic alternative. Unfortunately, this rule was rescinded in 2021, allowing copay accumulators even if a lower-cost generic was available.

In a positive turn of events, the US District Court of the District of Columbia overturned the 2021 rule in late 2023, reinstating the 2020 ban on copay accumulators. However, HHS has yet to enforce this ban.
 

Double Standard

Why is it that our federal government refrains from enforcing bans on copay accumulators for the American public, yet the US Office of Personnel Management (OPM) in its 2024 health plan for federal employees has explicitly stated that it “will decline any arrangements which may manipulate the prescription drug benefit design or incorporate any programs such as copay maximizers, copay optimizers, or other similar programs as these types of benefit designs are not in the best interest of enrollees or the Government.”

If such practices are deemed unsuitable for federal employees, why are they considered acceptable for the rest of the American population? This discrepancy raises important questions about healthcare equity.

In conclusion, the prevalence of medical bankruptcy in our country is a pressing issue that requires immediate attention. The introduction of copay accumulator programs and maximizers by PBMs has led to decreased adherence to needed medications, as well as delay in important medical procedures, exacerbating this situation. An across-the-board ban on these programs would offer immediate relief to many families that no longer can afford needed care.

It is clear that more needs to be done to ensure that all patients, regardless of their financial situation or the nature of their health insurance plan, can afford the healthcare they need. This includes ensuring that patients are not penalized for using manufacturer copay cards to help cover their costs. As we move forward, it is crucial that we continue to advocate for policies that prioritize the health and well-being of all patients.
 

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s vice president of Advocacy and Government Affairs and its immediate past president, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

The escalating costs of medications and the prevalence of medical bankruptcy in our country have drawn criticism from governments, regulators, and the media. Federal and state governments are exploring various strategies to mitigate this issue, including the Inflation Reduction Act (IRA) for drug price negotiations and the establishment of state Pharmaceutical Drug Affordability Boards (PDABs). However, it’s uncertain whether these measures will effectively reduce patients’ medication expenses, given the tendency of pharmacy benefit managers (PBMs) to favor more expensive drugs on their formularies and the implementation challenges faced by PDABs.

The question then arises: How can we promptly assist patients, especially those with multiple chronic conditions, in affording their healthcare? Many of these patients are enrolled in high-deductible plans and struggle to cover all their medical and pharmacy costs.

A significant obstacle to healthcare affordability emerged in 2018 with the introduction of Copay Accumulator Programs by PBMs. These programs prevent patients from applying manufacturer copay cards toward their deductible and maximum out-of-pocket (OOP) costs. The impact of these policies has been devastating, leading to decreased adherence to medications and delayed necessary medical procedures, such as colonoscopies. Copay accumulators do nothing to address the high cost of medical care. They merely shift the burden from insurance companies to patients.

There is a direct solution to help patients, particularly those burdened with high pharmacy bills, afford their medical care. It would be that all payments from patients, including manufacturer copay cards, count toward their deductible and maximum OOP costs. This should apply regardless of whether the insurance plan is fully funded or a self-insured employer plan. This would be an immediate step toward making healthcare more affordable for patients.
 

Copay Accumulator Programs

How did these detrimental policies, which have been proven to harm patients, originate? It’s interesting that health insurance policies for federal employees do not allow these programs and yet the federal government has done little to protect its citizens from these egregious policies. More on that later.

In 2018, insurance companies and PBMs conceived an idea to introduce what they called copay accumulator adjustment programs. These programs would prevent the use of manufacturer copay cards from counting toward patient deductibles or OOP maximums. They justified this by arguing that manufacturer copay cards encouraged patients to opt for higher-priced brand drugs when lower-cost generics were available.

However, data from IQVIA contradicts this claim. An analysis of copay card usage from 2013 to 2017 revealed that a mere 0.4% of these cards were used for brand-name drugs that had already lost their exclusivity. This indicates that the vast majority of copay cards were not being used to purchase more expensive brand-name drugs when cheaper, generic alternatives were available.

Another argument put forth by one of the large PBMs was that patients with high deductibles don’t have enough “skin in the game” due to their low premiums, and therefore don’t deserve to have their deductible covered by a copay card. This raises the question, “Does a patient with hemophilia or systemic lupus who can’t afford a low deductible plan not have ‘skin in the game’? Is that a fair assessment?” It’s disconcerting to see a multibillion-dollar company dictating who deserves to have their deductible covered. These policies clearly disproportionately harm patients with chronic illnesses, especially those with high deductibles. As a result, many organizations have labeled these policies as discriminatory.

Following the implementation of accumulator programs in 2018 and 2019, many patients were unaware that their copay cards weren’t contributing toward their deductibles. They were taken aback when specialty pharmacies informed them of owing substantial amounts because of unmet deductibles. Consequently, patients discontinued their medications, leading to disease progression and increased costs. The only downside for health insurers and PBMs was the negative publicity associated with patients losing medication access.
 

Maximizer Programs

By the end of 2019, the three major PBMs had devised a strategy to keep patients on their medication throughout the year, without counting copay cards toward the deductible, and found a way to profit more from these cards, sometimes quadrupling their value. This was the birth of the maximizer programs.

Maximizers exploit a “loophole” in the Affordable Care Act (ACA). The ACA defines Essential Healthcare Benefits (EHB); anything not listed as an EHB is deemed “non-essential.” As a result, neither personal payments nor copay cards count toward deductibles or OOP maximums. Patients were informed that neither their own money nor manufacturer copay cards would count toward their deductible/OOP max.

One of my patients was warned that without enrolling in the maximizer program through SaveOnSP (owned by Express Scripts), she would bear the full cost of the drug, and nothing would count toward her OOP max. Frightened, she enrolled and surrendered her manufacturer copay card to SaveOnSP. Maximizers pocket the maximum value of the copay card, even if it exceeds the insurance plan’s yearly cost share by threefold or more. To do this legally, PBMs increase the patient’s original cost share amount during the plan year to match the value of the manufacturer copay card.
 

Combating These Programs

Nineteen states, the District of Columbia, and Puerto Rico have outlawed copay accumulators in health plans under state jurisdiction. I personally testified in Louisiana, leading to a ban in our state. CSRO’s award-winning map tool can show if your state has passed the ban on copay accumulator programs. However, many states have not passed bans on copay accumulators and self-insured employer groups, which fall under the Department of Labor and not state regulation, are still unaffected. There is also proposed federal legislation, the “Help Ensure Lower Patient Copays Act,” that would prohibit the use of copay accumulators in exchange plans. Despite having bipartisan support, it is having a hard time getting across the finish line in Congress.

In 2020, the Department of Health and Human Services (HHS) issued a rule prohibiting accumulator programs in all plans if the product was a brand name without a generic alternative. Unfortunately, this rule was rescinded in 2021, allowing copay accumulators even if a lower-cost generic was available.

In a positive turn of events, the US District Court of the District of Columbia overturned the 2021 rule in late 2023, reinstating the 2020 ban on copay accumulators. However, HHS has yet to enforce this ban.
 

Double Standard

Why is it that our federal government refrains from enforcing bans on copay accumulators for the American public, yet the US Office of Personnel Management (OPM) in its 2024 health plan for federal employees has explicitly stated that it “will decline any arrangements which may manipulate the prescription drug benefit design or incorporate any programs such as copay maximizers, copay optimizers, or other similar programs as these types of benefit designs are not in the best interest of enrollees or the Government.”

If such practices are deemed unsuitable for federal employees, why are they considered acceptable for the rest of the American population? This discrepancy raises important questions about healthcare equity.

In conclusion, the prevalence of medical bankruptcy in our country is a pressing issue that requires immediate attention. The introduction of copay accumulator programs and maximizers by PBMs has led to decreased adherence to needed medications, as well as delay in important medical procedures, exacerbating this situation. An across-the-board ban on these programs would offer immediate relief to many families that no longer can afford needed care.

It is clear that more needs to be done to ensure that all patients, regardless of their financial situation or the nature of their health insurance plan, can afford the healthcare they need. This includes ensuring that patients are not penalized for using manufacturer copay cards to help cover their costs. As we move forward, it is crucial that we continue to advocate for policies that prioritize the health and well-being of all patients.
 

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s vice president of Advocacy and Government Affairs and its immediate past president, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

The escalating costs of medications and the prevalence of medical bankruptcy in our country have drawn criticism from governments, regulators, and the media. Federal and state governments are exploring various strategies to mitigate this issue, including the Inflation Reduction Act (IRA) for drug price negotiations and the establishment of state Pharmaceutical Drug Affordability Boards (PDABs). However, it’s uncertain whether these measures will effectively reduce patients’ medication expenses, given the tendency of pharmacy benefit managers (PBMs) to favor more expensive drugs on their formularies and the implementation challenges faced by PDABs.

The question then arises: How can we promptly assist patients, especially those with multiple chronic conditions, in affording their healthcare? Many of these patients are enrolled in high-deductible plans and struggle to cover all their medical and pharmacy costs.

A significant obstacle to healthcare affordability emerged in 2018 with the introduction of Copay Accumulator Programs by PBMs. These programs prevent patients from applying manufacturer copay cards toward their deductible and maximum out-of-pocket (OOP) costs. The impact of these policies has been devastating, leading to decreased adherence to medications and delayed necessary medical procedures, such as colonoscopies. Copay accumulators do nothing to address the high cost of medical care. They merely shift the burden from insurance companies to patients.

There is a direct solution to help patients, particularly those burdened with high pharmacy bills, afford their medical care. It would be that all payments from patients, including manufacturer copay cards, count toward their deductible and maximum OOP costs. This should apply regardless of whether the insurance plan is fully funded or a self-insured employer plan. This would be an immediate step toward making healthcare more affordable for patients.
 

Copay Accumulator Programs

How did these detrimental policies, which have been proven to harm patients, originate? It’s interesting that health insurance policies for federal employees do not allow these programs and yet the federal government has done little to protect its citizens from these egregious policies. More on that later.

In 2018, insurance companies and PBMs conceived an idea to introduce what they called copay accumulator adjustment programs. These programs would prevent the use of manufacturer copay cards from counting toward patient deductibles or OOP maximums. They justified this by arguing that manufacturer copay cards encouraged patients to opt for higher-priced brand drugs when lower-cost generics were available.

However, data from IQVIA contradicts this claim. An analysis of copay card usage from 2013 to 2017 revealed that a mere 0.4% of these cards were used for brand-name drugs that had already lost their exclusivity. This indicates that the vast majority of copay cards were not being used to purchase more expensive brand-name drugs when cheaper, generic alternatives were available.

Another argument put forth by one of the large PBMs was that patients with high deductibles don’t have enough “skin in the game” due to their low premiums, and therefore don’t deserve to have their deductible covered by a copay card. This raises the question, “Does a patient with hemophilia or systemic lupus who can’t afford a low deductible plan not have ‘skin in the game’? Is that a fair assessment?” It’s disconcerting to see a multibillion-dollar company dictating who deserves to have their deductible covered. These policies clearly disproportionately harm patients with chronic illnesses, especially those with high deductibles. As a result, many organizations have labeled these policies as discriminatory.

Following the implementation of accumulator programs in 2018 and 2019, many patients were unaware that their copay cards weren’t contributing toward their deductibles. They were taken aback when specialty pharmacies informed them of owing substantial amounts because of unmet deductibles. Consequently, patients discontinued their medications, leading to disease progression and increased costs. The only downside for health insurers and PBMs was the negative publicity associated with patients losing medication access.
 

Maximizer Programs

By the end of 2019, the three major PBMs had devised a strategy to keep patients on their medication throughout the year, without counting copay cards toward the deductible, and found a way to profit more from these cards, sometimes quadrupling their value. This was the birth of the maximizer programs.

Maximizers exploit a “loophole” in the Affordable Care Act (ACA). The ACA defines Essential Healthcare Benefits (EHB); anything not listed as an EHB is deemed “non-essential.” As a result, neither personal payments nor copay cards count toward deductibles or OOP maximums. Patients were informed that neither their own money nor manufacturer copay cards would count toward their deductible/OOP max.

One of my patients was warned that without enrolling in the maximizer program through SaveOnSP (owned by Express Scripts), she would bear the full cost of the drug, and nothing would count toward her OOP max. Frightened, she enrolled and surrendered her manufacturer copay card to SaveOnSP. Maximizers pocket the maximum value of the copay card, even if it exceeds the insurance plan’s yearly cost share by threefold or more. To do this legally, PBMs increase the patient’s original cost share amount during the plan year to match the value of the manufacturer copay card.
 

Combating These Programs

Nineteen states, the District of Columbia, and Puerto Rico have outlawed copay accumulators in health plans under state jurisdiction. I personally testified in Louisiana, leading to a ban in our state. CSRO’s award-winning map tool can show if your state has passed the ban on copay accumulator programs. However, many states have not passed bans on copay accumulators and self-insured employer groups, which fall under the Department of Labor and not state regulation, are still unaffected. There is also proposed federal legislation, the “Help Ensure Lower Patient Copays Act,” that would prohibit the use of copay accumulators in exchange plans. Despite having bipartisan support, it is having a hard time getting across the finish line in Congress.

In 2020, the Department of Health and Human Services (HHS) issued a rule prohibiting accumulator programs in all plans if the product was a brand name without a generic alternative. Unfortunately, this rule was rescinded in 2021, allowing copay accumulators even if a lower-cost generic was available.

In a positive turn of events, the US District Court of the District of Columbia overturned the 2021 rule in late 2023, reinstating the 2020 ban on copay accumulators. However, HHS has yet to enforce this ban.
 

Double Standard

Why is it that our federal government refrains from enforcing bans on copay accumulators for the American public, yet the US Office of Personnel Management (OPM) in its 2024 health plan for federal employees has explicitly stated that it “will decline any arrangements which may manipulate the prescription drug benefit design or incorporate any programs such as copay maximizers, copay optimizers, or other similar programs as these types of benefit designs are not in the best interest of enrollees or the Government.”

If such practices are deemed unsuitable for federal employees, why are they considered acceptable for the rest of the American population? This discrepancy raises important questions about healthcare equity.

In conclusion, the prevalence of medical bankruptcy in our country is a pressing issue that requires immediate attention. The introduction of copay accumulator programs and maximizers by PBMs has led to decreased adherence to needed medications, as well as delay in important medical procedures, exacerbating this situation. An across-the-board ban on these programs would offer immediate relief to many families that no longer can afford needed care.

It is clear that more needs to be done to ensure that all patients, regardless of their financial situation or the nature of their health insurance plan, can afford the healthcare they need. This includes ensuring that patients are not penalized for using manufacturer copay cards to help cover their costs. As we move forward, it is crucial that we continue to advocate for policies that prioritize the health and well-being of all patients.
 

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s vice president of Advocacy and Government Affairs and its immediate past president, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

CHICAGO — Being hormone receptor positive is generally a favorable prognostic factor in breast cancer, but that doesn’t seem to be the case in women with BRCA-associated tumors, according to a study presented at the American Society of Clinical Oncology annual meeting.

The conclusion is based on a large international study on how hormone receptor status impacts breast cancer outcomes in young women with germline BRCA pathological variants (PVs).

Overall, “hormone receptor positivity did not seem to have a strong positive prognostic value in young BRCA carriers” with early breast cancer, lead investigator Luca Arecco, MD, an oncology resident at the University of Genoa, Italy, said at the meeting.

Investigators reviewed the records of 4709 women ages 40 years or younger with stage 1-3 BRCA-associated invasive breast cancer treated from 2000 to 2020 at 78 centers in 28 countries across four continents. Median follow-up was about 8 years.
 

Weaker Prognostic Value in Hormone Receptor Status

They found, in general, that hormone receptor–positive breast cancer appears to be biologically more aggressive in patients with BRCA PVs than in the general breast cancer population, generating outcomes similar to those with hormone receptor-negative BRCA tumors.

Specifically, among patients with germline BRCA PVs, while hormone receptor–positive patients had a higher distant recurrence rate (13.1% vs. 9.6%) than hormone receptor–negative patients, 8-year disease free survival (65.8% and 63.4% respectively) and overall survival (a bit under 90% in both groups) were similar.

Hormone receptor–positive patients did have a lower rate of second primary breast cancers (9.1% versus 14.7%).

In the formal write-up of the results published shortly after the meeting in Annals of Oncology, the investigators concluded that “in young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor–positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.”

The team also found other differences between BRCA-associated breast cancer and sporadic disease. For instance, in the BRCA cohort, luminal A-like breast cancer had a worse long-term prognosis in their BRCA cohort than triple-negative or HER2-positive disease. Luminal A-like tumors are generally considered less aggressive, but in patients with BRCA PVs, “improving neoadjuvant chemotherapy … could be worthwhile,” the investigators said.

Also, although the risk of recurrence for sporadic hormone receptor–negative tumors is highest in the first few years, the team found that the risk in the hormone negative BRCA cohort progressively increased with longer follow-up, driven by the occurrence of second primary breast cancers, especially in patients with BRCA 1 PVs.
 

Greater Clarity in Prognosis in BRCA-Associated Breast Cancer

Overall, study discussant Lisa A. Carey, MD, a breast cancer specialist at the University of North Carolina at Chapel Hill, said, “we now know much more clearly the issues of prognosis in women who are very young and have germline BRCA-associated breast cancer,” about 12% of newly diagnosed cases.

“Young patients with germline BRCA-associated breast cancers have high relapse and high new primary risks, warranting comprehensive multimodality therapy,” she said.

A bit fewer than half of women in the study were hormone receptor–positive, and they tended to be patients with BRCA 2 PVs. The rest were hormone receptor–negative and tended to have BRCA 1 PVs.

Patients with hormone receptor–positive disease had grade 3 cancers in about 50% of cases, while patients with hormone receptor–negative disease had a grade 3 disease in over 80%.

Hormone receptor–positive patients were more likely to have nodal involvement and undergo mastectomies but less likely to receive chemotherapy than hormone receptor–negative patients. It’s likely that few patients in the review received PARP inhibitors, Dr. Carey noted.

Although overall survival at 8 years was similar in both groups, after that point “the prognosis of patients with hormone receptor–positive disease appeared to be worse … This appeared to occur earlier than that described in sporadic disease,” in which the worsening of survival in hormone receptor–positive disease occurs after a follow-up of at least 14-15 years, the investigators noted in their journal report.

The work was funded by the Italian Association for Cancer Research, Institut Jules Bordet, Korea Health Industry Development Institute, Australian National Health and Medical Council, Cancer Australia, US National Institute of Health, and others. Dr. Arecco had no disclosures. Dr. Carey and other coauthors disclosed research funding, speaker honoraria, and other financial relationships with AstraZeneca, Genentech/Roche, Lilly, and other pharmaceutical companies.

CHICAGO — Being hormone receptor positive is generally a favorable prognostic factor in breast cancer, but that doesn’t seem to be the case in women with BRCA-associated tumors, according to a study presented at the American Society of Clinical Oncology annual meeting.

The conclusion is based on a large international study on how hormone receptor status impacts breast cancer outcomes in young women with germline BRCA pathological variants (PVs).

Overall, “hormone receptor positivity did not seem to have a strong positive prognostic value in young BRCA carriers” with early breast cancer, lead investigator Luca Arecco, MD, an oncology resident at the University of Genoa, Italy, said at the meeting.

Investigators reviewed the records of 4709 women ages 40 years or younger with stage 1-3 BRCA-associated invasive breast cancer treated from 2000 to 2020 at 78 centers in 28 countries across four continents. Median follow-up was about 8 years.
 

Weaker Prognostic Value in Hormone Receptor Status

They found, in general, that hormone receptor–positive breast cancer appears to be biologically more aggressive in patients with BRCA PVs than in the general breast cancer population, generating outcomes similar to those with hormone receptor-negative BRCA tumors.

Specifically, among patients with germline BRCA PVs, while hormone receptor–positive patients had a higher distant recurrence rate (13.1% vs. 9.6%) than hormone receptor–negative patients, 8-year disease free survival (65.8% and 63.4% respectively) and overall survival (a bit under 90% in both groups) were similar.

Hormone receptor–positive patients did have a lower rate of second primary breast cancers (9.1% versus 14.7%).

In the formal write-up of the results published shortly after the meeting in Annals of Oncology, the investigators concluded that “in young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor–positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.”

The team also found other differences between BRCA-associated breast cancer and sporadic disease. For instance, in the BRCA cohort, luminal A-like breast cancer had a worse long-term prognosis in their BRCA cohort than triple-negative or HER2-positive disease. Luminal A-like tumors are generally considered less aggressive, but in patients with BRCA PVs, “improving neoadjuvant chemotherapy … could be worthwhile,” the investigators said.

Also, although the risk of recurrence for sporadic hormone receptor–negative tumors is highest in the first few years, the team found that the risk in the hormone negative BRCA cohort progressively increased with longer follow-up, driven by the occurrence of second primary breast cancers, especially in patients with BRCA 1 PVs.
 

Greater Clarity in Prognosis in BRCA-Associated Breast Cancer

Overall, study discussant Lisa A. Carey, MD, a breast cancer specialist at the University of North Carolina at Chapel Hill, said, “we now know much more clearly the issues of prognosis in women who are very young and have germline BRCA-associated breast cancer,” about 12% of newly diagnosed cases.

“Young patients with germline BRCA-associated breast cancers have high relapse and high new primary risks, warranting comprehensive multimodality therapy,” she said.

A bit fewer than half of women in the study were hormone receptor–positive, and they tended to be patients with BRCA 2 PVs. The rest were hormone receptor–negative and tended to have BRCA 1 PVs.

Patients with hormone receptor–positive disease had grade 3 cancers in about 50% of cases, while patients with hormone receptor–negative disease had a grade 3 disease in over 80%.

Hormone receptor–positive patients were more likely to have nodal involvement and undergo mastectomies but less likely to receive chemotherapy than hormone receptor–negative patients. It’s likely that few patients in the review received PARP inhibitors, Dr. Carey noted.

Although overall survival at 8 years was similar in both groups, after that point “the prognosis of patients with hormone receptor–positive disease appeared to be worse … This appeared to occur earlier than that described in sporadic disease,” in which the worsening of survival in hormone receptor–positive disease occurs after a follow-up of at least 14-15 years, the investigators noted in their journal report.

The work was funded by the Italian Association for Cancer Research, Institut Jules Bordet, Korea Health Industry Development Institute, Australian National Health and Medical Council, Cancer Australia, US National Institute of Health, and others. Dr. Arecco had no disclosures. Dr. Carey and other coauthors disclosed research funding, speaker honoraria, and other financial relationships with AstraZeneca, Genentech/Roche, Lilly, and other pharmaceutical companies.

CHICAGO — Being hormone receptor positive is generally a favorable prognostic factor in breast cancer, but that doesn’t seem to be the case in women with BRCA-associated tumors, according to a study presented at the American Society of Clinical Oncology annual meeting.

The conclusion is based on a large international study on how hormone receptor status impacts breast cancer outcomes in young women with germline BRCA pathological variants (PVs).

Overall, “hormone receptor positivity did not seem to have a strong positive prognostic value in young BRCA carriers” with early breast cancer, lead investigator Luca Arecco, MD, an oncology resident at the University of Genoa, Italy, said at the meeting.

Investigators reviewed the records of 4709 women ages 40 years or younger with stage 1-3 BRCA-associated invasive breast cancer treated from 2000 to 2020 at 78 centers in 28 countries across four continents. Median follow-up was about 8 years.
 

Weaker Prognostic Value in Hormone Receptor Status

They found, in general, that hormone receptor–positive breast cancer appears to be biologically more aggressive in patients with BRCA PVs than in the general breast cancer population, generating outcomes similar to those with hormone receptor-negative BRCA tumors.

Specifically, among patients with germline BRCA PVs, while hormone receptor–positive patients had a higher distant recurrence rate (13.1% vs. 9.6%) than hormone receptor–negative patients, 8-year disease free survival (65.8% and 63.4% respectively) and overall survival (a bit under 90% in both groups) were similar.

Hormone receptor–positive patients did have a lower rate of second primary breast cancers (9.1% versus 14.7%).

In the formal write-up of the results published shortly after the meeting in Annals of Oncology, the investigators concluded that “in young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor–positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.”

The team also found other differences between BRCA-associated breast cancer and sporadic disease. For instance, in the BRCA cohort, luminal A-like breast cancer had a worse long-term prognosis in their BRCA cohort than triple-negative or HER2-positive disease. Luminal A-like tumors are generally considered less aggressive, but in patients with BRCA PVs, “improving neoadjuvant chemotherapy … could be worthwhile,” the investigators said.

Also, although the risk of recurrence for sporadic hormone receptor–negative tumors is highest in the first few years, the team found that the risk in the hormone negative BRCA cohort progressively increased with longer follow-up, driven by the occurrence of second primary breast cancers, especially in patients with BRCA 1 PVs.
 

Greater Clarity in Prognosis in BRCA-Associated Breast Cancer

Overall, study discussant Lisa A. Carey, MD, a breast cancer specialist at the University of North Carolina at Chapel Hill, said, “we now know much more clearly the issues of prognosis in women who are very young and have germline BRCA-associated breast cancer,” about 12% of newly diagnosed cases.

“Young patients with germline BRCA-associated breast cancers have high relapse and high new primary risks, warranting comprehensive multimodality therapy,” she said.

A bit fewer than half of women in the study were hormone receptor–positive, and they tended to be patients with BRCA 2 PVs. The rest were hormone receptor–negative and tended to have BRCA 1 PVs.

Patients with hormone receptor–positive disease had grade 3 cancers in about 50% of cases, while patients with hormone receptor–negative disease had a grade 3 disease in over 80%.

Hormone receptor–positive patients were more likely to have nodal involvement and undergo mastectomies but less likely to receive chemotherapy than hormone receptor–negative patients. It’s likely that few patients in the review received PARP inhibitors, Dr. Carey noted.

Although overall survival at 8 years was similar in both groups, after that point “the prognosis of patients with hormone receptor–positive disease appeared to be worse … This appeared to occur earlier than that described in sporadic disease,” in which the worsening of survival in hormone receptor–positive disease occurs after a follow-up of at least 14-15 years, the investigators noted in their journal report.

The work was funded by the Italian Association for Cancer Research, Institut Jules Bordet, Korea Health Industry Development Institute, Australian National Health and Medical Council, Cancer Australia, US National Institute of Health, and others. Dr. Arecco had no disclosures. Dr. Carey and other coauthors disclosed research funding, speaker honoraria, and other financial relationships with AstraZeneca, Genentech/Roche, Lilly, and other pharmaceutical companies.