Clinician Reviews

An experimental topical phosphodiesterase 4 (PDE4) inhibitor showed superior efficacy to vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis, results from a phase 2a study showed.

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because “they can increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,” lead study author Lawrence F. Eichenfield, MD, of the dermatology department at the University of California, San Diego, and colleagues wrote. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has shown to be effective for plaque psoriasis and is well tolerated, and “it has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,” the researchers wrote.

For AD, crisaborole is the only approved topical PDE4 treatment, and it is associated with application site burning and stinging, they wrote.

An Experimental Alternative

The new study tested a topical PDE4 inhibitor known as PF-07038124, which is being developed by Pfizer. It is designed to be “a potent, oxaborole-based PDE4 inhibitor [that shows] immunomodulatory activity in T-cell–based assays, contributing to inhibition of [interleukin]-4 and IL-13; thus, it could provide therapeutic benefit in the treatment of AD and plaque psoriasis,” the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary end point was the percent change from baseline in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures of interest included treatment-emergent adverse events.

Overall, the mean age of the 104 patients was 43 years, 52.9%, were women, 3.8% were Asian, 12.5% were Black, and 83.7% were White. Most had moderate disease.

At week 6 in patients with AD, the PF-07038124 group showed statistically significantly greater improvement in the EASI total score, compared with vehicle group (−74.9% vs −35.5% respectively; least squares mean [LSM] difference, −39.4%; 90% CI, −58.8% to−20.1%]; P < .001).

Similarly, at week 6 in patients with plaque psoriasis, the PF-07038124 group demonstrated a significantly greater improvement in the PASI total score, compared with the vehicle group (LSM, −4.8; 90% CI, −6.2 to −3.4] vs 0.1; 90% CI, −1.5 to 1.7), for a difference of −4.9; 90% CI, −7.0 to −2.8; P < .001.

In safety outcomes, treatment-emergent adverse events were reported in 16 people receiving PF-07038124 and 26 people receiving a vehicle. The treatment-related adverse events were reported only in the vehicle groups across all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the trial, including its small size and the 6-week treatment period. “Unlike crisaborole, topical PF-07038124 was not associated with application site burning and stinging,” they noted. “To confirm persistence of efficacy and the safety profile of PF-07038124, long-term data should be collected in larger studies.”

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. He also has received grant support from, is consultant to, and/or is a member of the advisory board for many other pharmaceutical companies. Several other study authors reported similar disclosures.

An experimental topical phosphodiesterase 4 (PDE4) inhibitor showed superior efficacy to vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis, results from a phase 2a study showed.

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because “they can increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,” lead study author Lawrence F. Eichenfield, MD, of the dermatology department at the University of California, San Diego, and colleagues wrote. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has shown to be effective for plaque psoriasis and is well tolerated, and “it has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,” the researchers wrote.

For AD, crisaborole is the only approved topical PDE4 treatment, and it is associated with application site burning and stinging, they wrote.

An Experimental Alternative

The new study tested a topical PDE4 inhibitor known as PF-07038124, which is being developed by Pfizer. It is designed to be “a potent, oxaborole-based PDE4 inhibitor [that shows] immunomodulatory activity in T-cell–based assays, contributing to inhibition of [interleukin]-4 and IL-13; thus, it could provide therapeutic benefit in the treatment of AD and plaque psoriasis,” the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary end point was the percent change from baseline in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures of interest included treatment-emergent adverse events.

Overall, the mean age of the 104 patients was 43 years, 52.9%, were women, 3.8% were Asian, 12.5% were Black, and 83.7% were White. Most had moderate disease.

At week 6 in patients with AD, the PF-07038124 group showed statistically significantly greater improvement in the EASI total score, compared with vehicle group (−74.9% vs −35.5% respectively; least squares mean [LSM] difference, −39.4%; 90% CI, −58.8% to−20.1%]; P < .001).

Similarly, at week 6 in patients with plaque psoriasis, the PF-07038124 group demonstrated a significantly greater improvement in the PASI total score, compared with the vehicle group (LSM, −4.8; 90% CI, −6.2 to −3.4] vs 0.1; 90% CI, −1.5 to 1.7), for a difference of −4.9; 90% CI, −7.0 to −2.8; P < .001.

In safety outcomes, treatment-emergent adverse events were reported in 16 people receiving PF-07038124 and 26 people receiving a vehicle. The treatment-related adverse events were reported only in the vehicle groups across all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the trial, including its small size and the 6-week treatment period. “Unlike crisaborole, topical PF-07038124 was not associated with application site burning and stinging,” they noted. “To confirm persistence of efficacy and the safety profile of PF-07038124, long-term data should be collected in larger studies.”

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. He also has received grant support from, is consultant to, and/or is a member of the advisory board for many other pharmaceutical companies. Several other study authors reported similar disclosures.

An experimental topical phosphodiesterase 4 (PDE4) inhibitor showed superior efficacy to vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis, results from a phase 2a study showed.

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because “they can increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,” lead study author Lawrence F. Eichenfield, MD, of the dermatology department at the University of California, San Diego, and colleagues wrote. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has shown to be effective for plaque psoriasis and is well tolerated, and “it has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,” the researchers wrote.

For AD, crisaborole is the only approved topical PDE4 treatment, and it is associated with application site burning and stinging, they wrote.

An Experimental Alternative

The new study tested a topical PDE4 inhibitor known as PF-07038124, which is being developed by Pfizer. It is designed to be “a potent, oxaborole-based PDE4 inhibitor [that shows] immunomodulatory activity in T-cell–based assays, contributing to inhibition of [interleukin]-4 and IL-13; thus, it could provide therapeutic benefit in the treatment of AD and plaque psoriasis,” the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary end point was the percent change from baseline in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures of interest included treatment-emergent adverse events.

Overall, the mean age of the 104 patients was 43 years, 52.9%, were women, 3.8% were Asian, 12.5% were Black, and 83.7% were White. Most had moderate disease.

At week 6 in patients with AD, the PF-07038124 group showed statistically significantly greater improvement in the EASI total score, compared with vehicle group (−74.9% vs −35.5% respectively; least squares mean [LSM] difference, −39.4%; 90% CI, −58.8% to−20.1%]; P < .001).

Similarly, at week 6 in patients with plaque psoriasis, the PF-07038124 group demonstrated a significantly greater improvement in the PASI total score, compared with the vehicle group (LSM, −4.8; 90% CI, −6.2 to −3.4] vs 0.1; 90% CI, −1.5 to 1.7), for a difference of −4.9; 90% CI, −7.0 to −2.8; P < .001.

In safety outcomes, treatment-emergent adverse events were reported in 16 people receiving PF-07038124 and 26 people receiving a vehicle. The treatment-related adverse events were reported only in the vehicle groups across all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the trial, including its small size and the 6-week treatment period. “Unlike crisaborole, topical PF-07038124 was not associated with application site burning and stinging,” they noted. “To confirm persistence of efficacy and the safety profile of PF-07038124, long-term data should be collected in larger studies.”

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. He also has received grant support from, is consultant to, and/or is a member of the advisory board for many other pharmaceutical companies. Several other study authors reported similar disclosures.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Sandra Fryhofer, MD, highlights updates in the 2024 Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule.

The biggest change for 2024 is that you don’t need to wait till January 1, 2024, for these schedules go into effect. Both schedules were published and became available in November 2023 and became effective immediately. They include ACIP recommendations approved by the Centers for Disease Control and Prevention (CDC) director through October 23, 2023.

Subsequent recommendations (before publication of the 2025 schedule) will be added to the addendum, a new Step 5, Section 5 in the schedule. The addendum should make Affordable Care Act (ACA)–compliant insurance plans cover ACIP-recommended immunizations sooner.

This year’s schedule includes more vaccines with new recommendations and new color code keys for the schedule’s vaccine tables. The newest vaccine additions to the 2024 schedule include respiratory syncytial virus (RSV) vaccines, the mpox vaccine (Jynneos), a new MenACWY-MenB combo vaccine (Penbraya), and the new 2023-2024 formulation of the updated COVID vaccine (both mRNA and protein-based adjuvanted versions).

These are listed on the cover page (in alphabetical order) by name, abbreviation, and trade name. Vaccine-specific details can be found in the (Step 3) Notes section, also organized alphabetically.
 

The Tables

Step 1 is Table 1: Vaccinations by Age. Step 2 is Table 2: Vaccinations by Medical Conditions or Other Indications. The table names haven’t changed. However, their color code legends have been adjusted and refined. Also, the legends for the some of the same colors are not the same for both tables.

The order of and conditions covered in the columns on Table 2 have been reorganized.

Even for vaccines whose recommendations have not changed, the color code keys reflecting the recommendations have changed. For this reason, the 2024 version of Table 2 looks very different from the 2023 version. Also, much of the wording on overlays has been removed, which means you have to rely more heavily on the Notes section.

The color brown has been introduced on Table 2 to spotlight groups and conditions that require recurrent revaccination:

• Give Tdap in each and every pregnancy at 27-36 weeks.
• Revaccinate people living with HIV with MenACWY every 5 years.
• Revaccinate those with asplenia and/or complement deficiency with MenACWY every 5 years and MenB every 2-3 years.
• Stem cell transplant recipients need three doses of Hib.

Vaccine order is the same on both tables.

The rows for 2023-2024 formulations of COVID and flu vaccines are at the top of both tables are coded yellow, meaning everyone needs a dose of both vaccines.

Both tables have added a row for RSV vaccines and mpox vaccines.
 

Notes Section

The notes have been edited for clarity and reveal who needs what and when and include special vaccine-specific sections for special circumstances.

COVID vaccines. The COVID vaccine note embraces the updated 2023-2024 formula. Everyone aged 6 months or older needs a dose of the updated COVID vaccine. Specifics of who needs what (and when) depend on what they have already received, as well as their immune status. Detailed recommendations for both mRNA and protein-based adjuvanted versions are included in the notes.

RSV vaccines. The notes also give vital details about RSV vaccines for pregnant people and for older adults. There are two RSV vaccines. Both are preF RSV vaccines. They’re identified by trade names for clarity. Arexvy contains an adjuvant. Abrysvo does not contain an adjuvant. The RSV vaccine note explains that only Abyrsvo (the vaccine without the adjuvant) can be given to pregnant people, only at 32-36 weeks, and only to those whose baby would be born during RSV season.

ACIP recommends a dose of either vaccine for adults aged 60 or older, under shared clinical decision-making (meaning you and your patients have to discuss and decide). The notes link to additional guidance for making that decision.

Mpox vaccines. For the mpox vaccine, all adults in any age group at increased risk of getting mpox should get a two-dose series of the vaccine. The mpox vaccine notes include a list of mpox risk factors.
 

Other Features of the 2024 Adult Immunization Schedule

The schedule has useful links to helpful information:

• Vaccine information statements
• Complete ACIP recommendations
• CDC’s General Best Practice Guidelines for Immunizations.
• VAERS (CDC’s Vaccine Adverse Event Reporting System)

A new “Additional Information” section in the Notes links to:

• Travel vaccination requirements
• Best practices guidelines for vaccinating persons with immunodeficiency
• The National Vaccine Injury Compensation program (for resolving any vaccine injury claims)

The cover page has links to:

• CDC’s vaccine app
• QR code to access the schedule online.

With all these tools literally at your fingertips, there’s no reason not to know which vaccines your patients need and when. The challenge now is making it happen: getting those needed vaccines into arms.

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

This transcript has been edited for clarity.

Sandra Fryhofer, MD, highlights updates in the 2024 Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule.

The biggest change for 2024 is that you don’t need to wait till January 1, 2024, for these schedules go into effect. Both schedules were published and became available in November 2023 and became effective immediately. They include ACIP recommendations approved by the Centers for Disease Control and Prevention (CDC) director through October 23, 2023.

Subsequent recommendations (before publication of the 2025 schedule) will be added to the addendum, a new Step 5, Section 5 in the schedule. The addendum should make Affordable Care Act (ACA)–compliant insurance plans cover ACIP-recommended immunizations sooner.

This year’s schedule includes more vaccines with new recommendations and new color code keys for the schedule’s vaccine tables. The newest vaccine additions to the 2024 schedule include respiratory syncytial virus (RSV) vaccines, the mpox vaccine (Jynneos), a new MenACWY-MenB combo vaccine (Penbraya), and the new 2023-2024 formulation of the updated COVID vaccine (both mRNA and protein-based adjuvanted versions).

These are listed on the cover page (in alphabetical order) by name, abbreviation, and trade name. Vaccine-specific details can be found in the (Step 3) Notes section, also organized alphabetically.
 

The Tables

Step 1 is Table 1: Vaccinations by Age. Step 2 is Table 2: Vaccinations by Medical Conditions or Other Indications. The table names haven’t changed. However, their color code legends have been adjusted and refined. Also, the legends for the some of the same colors are not the same for both tables.

The order of and conditions covered in the columns on Table 2 have been reorganized.

Even for vaccines whose recommendations have not changed, the color code keys reflecting the recommendations have changed. For this reason, the 2024 version of Table 2 looks very different from the 2023 version. Also, much of the wording on overlays has been removed, which means you have to rely more heavily on the Notes section.

The color brown has been introduced on Table 2 to spotlight groups and conditions that require recurrent revaccination:

• Give Tdap in each and every pregnancy at 27-36 weeks.
• Revaccinate people living with HIV with MenACWY every 5 years.
• Revaccinate those with asplenia and/or complement deficiency with MenACWY every 5 years and MenB every 2-3 years.
• Stem cell transplant recipients need three doses of Hib.

Vaccine order is the same on both tables.

The rows for 2023-2024 formulations of COVID and flu vaccines are at the top of both tables are coded yellow, meaning everyone needs a dose of both vaccines.

Both tables have added a row for RSV vaccines and mpox vaccines.
 

Notes Section

The notes have been edited for clarity and reveal who needs what and when and include special vaccine-specific sections for special circumstances.

COVID vaccines. The COVID vaccine note embraces the updated 2023-2024 formula. Everyone aged 6 months or older needs a dose of the updated COVID vaccine. Specifics of who needs what (and when) depend on what they have already received, as well as their immune status. Detailed recommendations for both mRNA and protein-based adjuvanted versions are included in the notes.

RSV vaccines. The notes also give vital details about RSV vaccines for pregnant people and for older adults. There are two RSV vaccines. Both are preF RSV vaccines. They’re identified by trade names for clarity. Arexvy contains an adjuvant. Abrysvo does not contain an adjuvant. The RSV vaccine note explains that only Abyrsvo (the vaccine without the adjuvant) can be given to pregnant people, only at 32-36 weeks, and only to those whose baby would be born during RSV season.

ACIP recommends a dose of either vaccine for adults aged 60 or older, under shared clinical decision-making (meaning you and your patients have to discuss and decide). The notes link to additional guidance for making that decision.

Mpox vaccines. For the mpox vaccine, all adults in any age group at increased risk of getting mpox should get a two-dose series of the vaccine. The mpox vaccine notes include a list of mpox risk factors.
 

Other Features of the 2024 Adult Immunization Schedule

The schedule has useful links to helpful information:

• Vaccine information statements
• Complete ACIP recommendations
• CDC’s General Best Practice Guidelines for Immunizations.
• VAERS (CDC’s Vaccine Adverse Event Reporting System)

A new “Additional Information” section in the Notes links to:

• Travel vaccination requirements
• Best practices guidelines for vaccinating persons with immunodeficiency
• The National Vaccine Injury Compensation program (for resolving any vaccine injury claims)

The cover page has links to:

• CDC’s vaccine app
• QR code to access the schedule online.

With all these tools literally at your fingertips, there’s no reason not to know which vaccines your patients need and when. The challenge now is making it happen: getting those needed vaccines into arms.

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

This transcript has been edited for clarity.

Sandra Fryhofer, MD, highlights updates in the 2024 Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule.

The biggest change for 2024 is that you don’t need to wait till January 1, 2024, for these schedules go into effect. Both schedules were published and became available in November 2023 and became effective immediately. They include ACIP recommendations approved by the Centers for Disease Control and Prevention (CDC) director through October 23, 2023.

Subsequent recommendations (before publication of the 2025 schedule) will be added to the addendum, a new Step 5, Section 5 in the schedule. The addendum should make Affordable Care Act (ACA)–compliant insurance plans cover ACIP-recommended immunizations sooner.

This year’s schedule includes more vaccines with new recommendations and new color code keys for the schedule’s vaccine tables. The newest vaccine additions to the 2024 schedule include respiratory syncytial virus (RSV) vaccines, the mpox vaccine (Jynneos), a new MenACWY-MenB combo vaccine (Penbraya), and the new 2023-2024 formulation of the updated COVID vaccine (both mRNA and protein-based adjuvanted versions).

These are listed on the cover page (in alphabetical order) by name, abbreviation, and trade name. Vaccine-specific details can be found in the (Step 3) Notes section, also organized alphabetically.
 

The Tables

Step 1 is Table 1: Vaccinations by Age. Step 2 is Table 2: Vaccinations by Medical Conditions or Other Indications. The table names haven’t changed. However, their color code legends have been adjusted and refined. Also, the legends for the some of the same colors are not the same for both tables.

The order of and conditions covered in the columns on Table 2 have been reorganized.

Even for vaccines whose recommendations have not changed, the color code keys reflecting the recommendations have changed. For this reason, the 2024 version of Table 2 looks very different from the 2023 version. Also, much of the wording on overlays has been removed, which means you have to rely more heavily on the Notes section.

The color brown has been introduced on Table 2 to spotlight groups and conditions that require recurrent revaccination:

• Give Tdap in each and every pregnancy at 27-36 weeks.
• Revaccinate people living with HIV with MenACWY every 5 years.
• Revaccinate those with asplenia and/or complement deficiency with MenACWY every 5 years and MenB every 2-3 years.
• Stem cell transplant recipients need three doses of Hib.

Vaccine order is the same on both tables.

The rows for 2023-2024 formulations of COVID and flu vaccines are at the top of both tables are coded yellow, meaning everyone needs a dose of both vaccines.

Both tables have added a row for RSV vaccines and mpox vaccines.
 

Notes Section

The notes have been edited for clarity and reveal who needs what and when and include special vaccine-specific sections for special circumstances.

COVID vaccines. The COVID vaccine note embraces the updated 2023-2024 formula. Everyone aged 6 months or older needs a dose of the updated COVID vaccine. Specifics of who needs what (and when) depend on what they have already received, as well as their immune status. Detailed recommendations for both mRNA and protein-based adjuvanted versions are included in the notes.

RSV vaccines. The notes also give vital details about RSV vaccines for pregnant people and for older adults. There are two RSV vaccines. Both are preF RSV vaccines. They’re identified by trade names for clarity. Arexvy contains an adjuvant. Abrysvo does not contain an adjuvant. The RSV vaccine note explains that only Abyrsvo (the vaccine without the adjuvant) can be given to pregnant people, only at 32-36 weeks, and only to those whose baby would be born during RSV season.

ACIP recommends a dose of either vaccine for adults aged 60 or older, under shared clinical decision-making (meaning you and your patients have to discuss and decide). The notes link to additional guidance for making that decision.

Mpox vaccines. For the mpox vaccine, all adults in any age group at increased risk of getting mpox should get a two-dose series of the vaccine. The mpox vaccine notes include a list of mpox risk factors.
 

Other Features of the 2024 Adult Immunization Schedule

The schedule has useful links to helpful information:

• Vaccine information statements
• Complete ACIP recommendations
• CDC’s General Best Practice Guidelines for Immunizations.
• VAERS (CDC’s Vaccine Adverse Event Reporting System)

A new “Additional Information” section in the Notes links to:

• Travel vaccination requirements
• Best practices guidelines for vaccinating persons with immunodeficiency
• The National Vaccine Injury Compensation program (for resolving any vaccine injury claims)

The cover page has links to:

• CDC’s vaccine app
• QR code to access the schedule online.

With all these tools literally at your fingertips, there’s no reason not to know which vaccines your patients need and when. The challenge now is making it happen: getting those needed vaccines into arms.

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

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

With so many treatment options available for atopic dermatitis (AD) and more in the pipeline, one common question Raj Chovatiya, MD, PhD, hears from his fellow dermatologists is: How do I choose the right therapy for my patients?

“There isn’t going to be a one-size-fits-all approach, and it may be impossible to differentiate, given that these agents are not likely to be studied head-to-head,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Dr. Chovatiya

He shared a list of factors to consider when engaged in shared decision-making with patients about their AD treatment options. These include:

• Severity of disease (mild vs moderate vs severe).
• Extent of disease (low vs high body surface area).
• Rapidity of drug onset (hours vs days vs weeks).
• Depth of response based on different endpoints such as itch and number of lesions.
• Long-term efficacy (durability on treatment vs off treatment).
• Adverse events (cutaneous vs systemic).
• Black box warnings (present vs absent).
• Tolerance (selective areas vs the entire skin).
• Vehicle (ointment vs cream).
• Patient preference. “This may be the biggest driver; what do patients want?” Dr. Chovatiya said.
• Access to the drug. Is it easily obtainable for the patient?

He concluded his remarks by posing a question to attendees: “Are we closer to living in a topical steroid–free world for AD? Is that what we want?” he asked. “I wholeheartedly say that’s what we’ve been working toward all these years, and we should keep up the good fight. We have more data for targeted therapy to treat very specific disease with very specific outcomes and endpoints, because I think that’s [what] we all dream about in dermatology.”

Dr. Chovatiya disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies.

With so many treatment options available for atopic dermatitis (AD) and more in the pipeline, one common question Raj Chovatiya, MD, PhD, hears from his fellow dermatologists is: How do I choose the right therapy for my patients?

“There isn’t going to be a one-size-fits-all approach, and it may be impossible to differentiate, given that these agents are not likely to be studied head-to-head,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Dr. Chovatiya

He shared a list of factors to consider when engaged in shared decision-making with patients about their AD treatment options. These include:

• Severity of disease (mild vs moderate vs severe).
• Extent of disease (low vs high body surface area).
• Rapidity of drug onset (hours vs days vs weeks).
• Depth of response based on different endpoints such as itch and number of lesions.
• Long-term efficacy (durability on treatment vs off treatment).
• Adverse events (cutaneous vs systemic).
• Black box warnings (present vs absent).
• Tolerance (selective areas vs the entire skin).
• Vehicle (ointment vs cream).
• Patient preference. “This may be the biggest driver; what do patients want?” Dr. Chovatiya said.
• Access to the drug. Is it easily obtainable for the patient?

He concluded his remarks by posing a question to attendees: “Are we closer to living in a topical steroid–free world for AD? Is that what we want?” he asked. “I wholeheartedly say that’s what we’ve been working toward all these years, and we should keep up the good fight. We have more data for targeted therapy to treat very specific disease with very specific outcomes and endpoints, because I think that’s [what] we all dream about in dermatology.”

Dr. Chovatiya disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies.

With so many treatment options available for atopic dermatitis (AD) and more in the pipeline, one common question Raj Chovatiya, MD, PhD, hears from his fellow dermatologists is: How do I choose the right therapy for my patients?

“There isn’t going to be a one-size-fits-all approach, and it may be impossible to differentiate, given that these agents are not likely to be studied head-to-head,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Dr. Chovatiya

He shared a list of factors to consider when engaged in shared decision-making with patients about their AD treatment options. These include:

• Severity of disease (mild vs moderate vs severe).
• Extent of disease (low vs high body surface area).
• Rapidity of drug onset (hours vs days vs weeks).
• Depth of response based on different endpoints such as itch and number of lesions.
• Long-term efficacy (durability on treatment vs off treatment).
• Adverse events (cutaneous vs systemic).
• Black box warnings (present vs absent).
• Tolerance (selective areas vs the entire skin).
• Vehicle (ointment vs cream).
• Patient preference. “This may be the biggest driver; what do patients want?” Dr. Chovatiya said.
• Access to the drug. Is it easily obtainable for the patient?

He concluded his remarks by posing a question to attendees: “Are we closer to living in a topical steroid–free world for AD? Is that what we want?” he asked. “I wholeheartedly say that’s what we’ve been working toward all these years, and we should keep up the good fight. We have more data for targeted therapy to treat very specific disease with very specific outcomes and endpoints, because I think that’s [what] we all dream about in dermatology.”

Dr. Chovatiya disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies.

Safety data spanning up to 5 years from clinical trials of adolescents and adults using 15 mg or 30 mg of upadacitinib to treat moderate to severe atopic dermatitis (AD) indicates that rates of treatment-emergent adverse events remained low and consistent, with no new safety risks identified, underscoring the medication’s stable safety profile over an extended duration.

Those are among the key findings from an integrated analysis of long-term upadacitinib use presented by Christopher G. Bunick, MD, PhD, during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis Virtual Conference. Upadacitinib (Rinvoq) is an oral Janus kinase (JAK) inhibitor, approved by the Food and Drug Administration for adults and pediatric patients aged 12 years of age and older with refractory, moderate to severe AD in January 2022.

“What makes this study special is that these patients are followed for 260 weeks, or 5 years, and it encompasses over 7,000 patient-years of exposure,” said Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut. “This is a milestone because it’s the longest safety study ever published for any systemic drug for AD.”

He and his colleagues evaluated the safety data for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate to severe AD, based on the results of integrated data from three ongoing global multicenter phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. Patients in the trials were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At week 16, patients receiving 15 mg or 30 mg upadacitinib during the double-blind period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were randomized 1:1 to receive either 15 mg or 30 mg upadacitinib in the BE period. The integrated analysis included 2683 patients (529 adolescents and 2154 adults) who received at least one dose of upadacitinib. Of these, 1337 received the 15-mg dose, while 1346 received the 30-mg dose. The researchers analyzed treatment-emergent events of special interest as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different follow-up durations.

According to Dr. Bunick, researchers often refer to “100 patient-years” in safety analyses to measure how common certain events are. “It is a straightforward way to convey the collective experience of the study’s participants over time,” he told this news organization. “For instance, if 100 patients are each monitored for 1 year, or 50 patients for 2 years each, both scenarios amount to 100 patient-years. This metric allows clinicians to understand how often certain adverse events occur across a diverse group over a specific time frame, providing a clear picture of long-term safety.”

Upadacitinib trials in atopic dermatitis have included diverse patient groups with varying risk factors. “Patients were not cherry-picked,” he said. “What I mean by that is that about 50% of patients enrolled in these trials had, at baseline, at least one cardiovascular risk factor: about 30% used tobacco; 10% had hypertension, and 5% had a history of a cardiovascular event.” In addition, about 15% were over age 50 with one cardiovascular risk factor and about 20% had a body mass index (BMI) greater than 30 kg/m². Among women in the study, about 20% were on oral contraceptives, yet none developed a venous thromboembolism (VTE).

In the integrated analysis, the rate of treatment-emergent adverse events that led to discontinuation of upadacitinib was about 4.2 events per 100 PY, “meaning that this medicine shows durability,” Dr. Bunick said. “Very few people are discontinuing due to adverse events.”

Serious and opportunistic infections ranged from 1.6 to 2.8 events per 100 PY, but these were stable across the 1- to 5-year time points. The rates of active TB were less than 0.1 per 100 PY, while the rates of herpes zoster ranged from 3.5 to 5.5 events per 100 PY. “The key take-home point here is that 5% or less of the patients at baseline had received the shingles vaccine, so it’s very important to talk to patients about receiving the shingles vaccine before they go on upadacitinib,” Dr. Bunick advised, because “this could reduce risk of herpes zoster occurring in upadacitinib-treated patients substantially.”

In other findings, incidence rates of nonmelanoma skin cancer (NMSC) ranged between 0.3 and 0.4 per 100 PY, while the rate of malignancy excluding NMSC ranged between 0.3 and 0.4 per 100 PY. Meanwhile, the rates of gastrointestinal perforations and VTE stood at 0.1 per 100 PY or lower, and MACE incidence rates ranged from 0.1 to 0.2 per 100 PY.

During his presentation, Dr. Bunick compared findings related to malignancy (excluding NMSC), MACE, and VTE to other published real-world background rates observed in moderate to severe AD populations. He noted that, while the malignancy rate in the current trial ranged from 0.3 to 0.4 per 100 PY, an observational study of more than 66,000 AD patients in the United Kingdom reported a malignancy (excluding NMSC) background incidence rate of 0.33 per 100 PY, and SEER data estimate that the malignancy incidence rate in the US general population is 0.45 per 100 PY. “Therefore, patients on upadacitinib at the 5-year mark are right at the AD population baseline risk,” he said.

And while the incidence rate of MACE in the current trial ranged from less than 0.1 to 0.2 per 100 PY, the background incidence rate of MACE in a Danish observational study of more than 2,500 patients with moderate to severe AD was 0.63 per 100 PY. “This suggests that there may be an anti-inflammatory and even a cardiovascular protective effect for patients on upadacitinib,” Dr. Bunick said.

As for VTE, the incidence rate in the current trial was 0.1 per 100 PY, but VTE background incidence rate observed in a moderate to severe AD population in the United States is 0.31 per 100 PY. “Again, this suggests anti-inflammatory and cardiovascular protective effects of upadacitinib in AD patients at the 5-year mark,” he said. “Reporting of MACE, VTE, and malignancy (excluding NMSC) in upadacitinib phase 3 clinical trials for AD generally reflects the background observations of these events in the AD population.”

He acknowledged certain limitations of the study, including the fact that observational data may overestimate the risk of adverse events.

Discussing the incidence rates for MACE, VTE, and malignancy in upadacitinib AD trials, Dr. Bunick remarked, “these are rock-bottom rates that have been low through 5 years of treatment.”

Dr. Bunick disclosed that he has received grant or research support from AbbVie (the manufacturer of upadacitinib), Almirall, Ortho Dermatologics, Timber, and Palvella. He is also a consultant and/or an adviser to AbbVie, Almirall, Apogee, Connect Bropharma, Arcutis, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, Ortho Dermatologics, Leo Pharma, and UCB.

Safety data spanning up to 5 years from clinical trials of adolescents and adults using 15 mg or 30 mg of upadacitinib to treat moderate to severe atopic dermatitis (AD) indicates that rates of treatment-emergent adverse events remained low and consistent, with no new safety risks identified, underscoring the medication’s stable safety profile over an extended duration.

Those are among the key findings from an integrated analysis of long-term upadacitinib use presented by Christopher G. Bunick, MD, PhD, during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis Virtual Conference. Upadacitinib (Rinvoq) is an oral Janus kinase (JAK) inhibitor, approved by the Food and Drug Administration for adults and pediatric patients aged 12 years of age and older with refractory, moderate to severe AD in January 2022.

“What makes this study special is that these patients are followed for 260 weeks, or 5 years, and it encompasses over 7,000 patient-years of exposure,” said Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut. “This is a milestone because it’s the longest safety study ever published for any systemic drug for AD.”

He and his colleagues evaluated the safety data for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate to severe AD, based on the results of integrated data from three ongoing global multicenter phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. Patients in the trials were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At week 16, patients receiving 15 mg or 30 mg upadacitinib during the double-blind period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were randomized 1:1 to receive either 15 mg or 30 mg upadacitinib in the BE period. The integrated analysis included 2683 patients (529 adolescents and 2154 adults) who received at least one dose of upadacitinib. Of these, 1337 received the 15-mg dose, while 1346 received the 30-mg dose. The researchers analyzed treatment-emergent events of special interest as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different follow-up durations.

According to Dr. Bunick, researchers often refer to “100 patient-years” in safety analyses to measure how common certain events are. “It is a straightforward way to convey the collective experience of the study’s participants over time,” he told this news organization. “For instance, if 100 patients are each monitored for 1 year, or 50 patients for 2 years each, both scenarios amount to 100 patient-years. This metric allows clinicians to understand how often certain adverse events occur across a diverse group over a specific time frame, providing a clear picture of long-term safety.”

Upadacitinib trials in atopic dermatitis have included diverse patient groups with varying risk factors. “Patients were not cherry-picked,” he said. “What I mean by that is that about 50% of patients enrolled in these trials had, at baseline, at least one cardiovascular risk factor: about 30% used tobacco; 10% had hypertension, and 5% had a history of a cardiovascular event.” In addition, about 15% were over age 50 with one cardiovascular risk factor and about 20% had a body mass index (BMI) greater than 30 kg/m². Among women in the study, about 20% were on oral contraceptives, yet none developed a venous thromboembolism (VTE).

In the integrated analysis, the rate of treatment-emergent adverse events that led to discontinuation of upadacitinib was about 4.2 events per 100 PY, “meaning that this medicine shows durability,” Dr. Bunick said. “Very few people are discontinuing due to adverse events.”

Serious and opportunistic infections ranged from 1.6 to 2.8 events per 100 PY, but these were stable across the 1- to 5-year time points. The rates of active TB were less than 0.1 per 100 PY, while the rates of herpes zoster ranged from 3.5 to 5.5 events per 100 PY. “The key take-home point here is that 5% or less of the patients at baseline had received the shingles vaccine, so it’s very important to talk to patients about receiving the shingles vaccine before they go on upadacitinib,” Dr. Bunick advised, because “this could reduce risk of herpes zoster occurring in upadacitinib-treated patients substantially.”

In other findings, incidence rates of nonmelanoma skin cancer (NMSC) ranged between 0.3 and 0.4 per 100 PY, while the rate of malignancy excluding NMSC ranged between 0.3 and 0.4 per 100 PY. Meanwhile, the rates of gastrointestinal perforations and VTE stood at 0.1 per 100 PY or lower, and MACE incidence rates ranged from 0.1 to 0.2 per 100 PY.

During his presentation, Dr. Bunick compared findings related to malignancy (excluding NMSC), MACE, and VTE to other published real-world background rates observed in moderate to severe AD populations. He noted that, while the malignancy rate in the current trial ranged from 0.3 to 0.4 per 100 PY, an observational study of more than 66,000 AD patients in the United Kingdom reported a malignancy (excluding NMSC) background incidence rate of 0.33 per 100 PY, and SEER data estimate that the malignancy incidence rate in the US general population is 0.45 per 100 PY. “Therefore, patients on upadacitinib at the 5-year mark are right at the AD population baseline risk,” he said.

And while the incidence rate of MACE in the current trial ranged from less than 0.1 to 0.2 per 100 PY, the background incidence rate of MACE in a Danish observational study of more than 2,500 patients with moderate to severe AD was 0.63 per 100 PY. “This suggests that there may be an anti-inflammatory and even a cardiovascular protective effect for patients on upadacitinib,” Dr. Bunick said.

As for VTE, the incidence rate in the current trial was 0.1 per 100 PY, but VTE background incidence rate observed in a moderate to severe AD population in the United States is 0.31 per 100 PY. “Again, this suggests anti-inflammatory and cardiovascular protective effects of upadacitinib in AD patients at the 5-year mark,” he said. “Reporting of MACE, VTE, and malignancy (excluding NMSC) in upadacitinib phase 3 clinical trials for AD generally reflects the background observations of these events in the AD population.”

He acknowledged certain limitations of the study, including the fact that observational data may overestimate the risk of adverse events.

Discussing the incidence rates for MACE, VTE, and malignancy in upadacitinib AD trials, Dr. Bunick remarked, “these are rock-bottom rates that have been low through 5 years of treatment.”

Dr. Bunick disclosed that he has received grant or research support from AbbVie (the manufacturer of upadacitinib), Almirall, Ortho Dermatologics, Timber, and Palvella. He is also a consultant and/or an adviser to AbbVie, Almirall, Apogee, Connect Bropharma, Arcutis, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, Ortho Dermatologics, Leo Pharma, and UCB.

Safety data spanning up to 5 years from clinical trials of adolescents and adults using 15 mg or 30 mg of upadacitinib to treat moderate to severe atopic dermatitis (AD) indicates that rates of treatment-emergent adverse events remained low and consistent, with no new safety risks identified, underscoring the medication’s stable safety profile over an extended duration.

Those are among the key findings from an integrated analysis of long-term upadacitinib use presented by Christopher G. Bunick, MD, PhD, during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis Virtual Conference. Upadacitinib (Rinvoq) is an oral Janus kinase (JAK) inhibitor, approved by the Food and Drug Administration for adults and pediatric patients aged 12 years of age and older with refractory, moderate to severe AD in January 2022.

“What makes this study special is that these patients are followed for 260 weeks, or 5 years, and it encompasses over 7,000 patient-years of exposure,” said Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut. “This is a milestone because it’s the longest safety study ever published for any systemic drug for AD.”

He and his colleagues evaluated the safety data for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate to severe AD, based on the results of integrated data from three ongoing global multicenter phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. Patients in the trials were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At week 16, patients receiving 15 mg or 30 mg upadacitinib during the double-blind period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were randomized 1:1 to receive either 15 mg or 30 mg upadacitinib in the BE period. The integrated analysis included 2683 patients (529 adolescents and 2154 adults) who received at least one dose of upadacitinib. Of these, 1337 received the 15-mg dose, while 1346 received the 30-mg dose. The researchers analyzed treatment-emergent events of special interest as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different follow-up durations.

According to Dr. Bunick, researchers often refer to “100 patient-years” in safety analyses to measure how common certain events are. “It is a straightforward way to convey the collective experience of the study’s participants over time,” he told this news organization. “For instance, if 100 patients are each monitored for 1 year, or 50 patients for 2 years each, both scenarios amount to 100 patient-years. This metric allows clinicians to understand how often certain adverse events occur across a diverse group over a specific time frame, providing a clear picture of long-term safety.”

Upadacitinib trials in atopic dermatitis have included diverse patient groups with varying risk factors. “Patients were not cherry-picked,” he said. “What I mean by that is that about 50% of patients enrolled in these trials had, at baseline, at least one cardiovascular risk factor: about 30% used tobacco; 10% had hypertension, and 5% had a history of a cardiovascular event.” In addition, about 15% were over age 50 with one cardiovascular risk factor and about 20% had a body mass index (BMI) greater than 30 kg/m². Among women in the study, about 20% were on oral contraceptives, yet none developed a venous thromboembolism (VTE).

In the integrated analysis, the rate of treatment-emergent adverse events that led to discontinuation of upadacitinib was about 4.2 events per 100 PY, “meaning that this medicine shows durability,” Dr. Bunick said. “Very few people are discontinuing due to adverse events.”

Serious and opportunistic infections ranged from 1.6 to 2.8 events per 100 PY, but these were stable across the 1- to 5-year time points. The rates of active TB were less than 0.1 per 100 PY, while the rates of herpes zoster ranged from 3.5 to 5.5 events per 100 PY. “The key take-home point here is that 5% or less of the patients at baseline had received the shingles vaccine, so it’s very important to talk to patients about receiving the shingles vaccine before they go on upadacitinib,” Dr. Bunick advised, because “this could reduce risk of herpes zoster occurring in upadacitinib-treated patients substantially.”

In other findings, incidence rates of nonmelanoma skin cancer (NMSC) ranged between 0.3 and 0.4 per 100 PY, while the rate of malignancy excluding NMSC ranged between 0.3 and 0.4 per 100 PY. Meanwhile, the rates of gastrointestinal perforations and VTE stood at 0.1 per 100 PY or lower, and MACE incidence rates ranged from 0.1 to 0.2 per 100 PY.

During his presentation, Dr. Bunick compared findings related to malignancy (excluding NMSC), MACE, and VTE to other published real-world background rates observed in moderate to severe AD populations. He noted that, while the malignancy rate in the current trial ranged from 0.3 to 0.4 per 100 PY, an observational study of more than 66,000 AD patients in the United Kingdom reported a malignancy (excluding NMSC) background incidence rate of 0.33 per 100 PY, and SEER data estimate that the malignancy incidence rate in the US general population is 0.45 per 100 PY. “Therefore, patients on upadacitinib at the 5-year mark are right at the AD population baseline risk,” he said.

And while the incidence rate of MACE in the current trial ranged from less than 0.1 to 0.2 per 100 PY, the background incidence rate of MACE in a Danish observational study of more than 2,500 patients with moderate to severe AD was 0.63 per 100 PY. “This suggests that there may be an anti-inflammatory and even a cardiovascular protective effect for patients on upadacitinib,” Dr. Bunick said.

As for VTE, the incidence rate in the current trial was 0.1 per 100 PY, but VTE background incidence rate observed in a moderate to severe AD population in the United States is 0.31 per 100 PY. “Again, this suggests anti-inflammatory and cardiovascular protective effects of upadacitinib in AD patients at the 5-year mark,” he said. “Reporting of MACE, VTE, and malignancy (excluding NMSC) in upadacitinib phase 3 clinical trials for AD generally reflects the background observations of these events in the AD population.”

He acknowledged certain limitations of the study, including the fact that observational data may overestimate the risk of adverse events.

Discussing the incidence rates for MACE, VTE, and malignancy in upadacitinib AD trials, Dr. Bunick remarked, “these are rock-bottom rates that have been low through 5 years of treatment.”

Dr. Bunick disclosed that he has received grant or research support from AbbVie (the manufacturer of upadacitinib), Almirall, Ortho Dermatologics, Timber, and Palvella. He is also a consultant and/or an adviser to AbbVie, Almirall, Apogee, Connect Bropharma, Arcutis, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, Ortho Dermatologics, Leo Pharma, and UCB.

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

Walking is a simple, cost-free form of exercise that benefits physical, social, and mental health in many ways. Several clinical trials have shown that walking regularly is associated with a lower risk for cardiovascular events and all-cause mortality, and having a higher daily step count is linked to a decreased risk for premature death.

Walking and Diabetes

In recent years, the link between walking speed and the risk for multiple health problems has sparked keen interest. Data suggest that a faster walking pace may have a greater physiological response and may be associated with more favorable health advantages than a slow walking pace. A previous meta-analysis of eight cohort studies suggested that individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk for stroke than those in the slowest walking-pace category (median = 1.6 km/h). The risk for the former decreased by 13% for every 1 km/h increment in baseline walking pace.

Type 2 diabetes (T2D) is one of the most common metabolic diseases in the world. People with this type of diabetes have an increased risk for microvascular and macrovascular complications and a shorter life expectancy. Approximately 537 million adults are estimated to be living with diabetes worldwide, and this number is expected to reach 783 million by 2045.

Physical activity is an essential component of T2D prevention programs and can favorably affect blood sugar control. A meta-analysis of cohort studies showed that being physically active was associated with a 35% reduction in the risk of acquiring T2D in the general population, and regular walking was associated with a 15% reduction in the risk of developing T2D.

However, no studies have investigated the link between different walking speeds and the risk for T2D. A team from the Research Center at the Semnan University of Medical Sciences in Iran carried out a systematic review of the association between walking speed and the risk of developing T2D in adults; this review was published in the British Journal of Sports Medicine.
 

10 Cohort Studies

This systematic review used publications (1999-2022) available in the usual data sources (PubMed, Scopus, CENTRAL, and Web of Science). Random-effects meta-analyses were used to calculate relative risk (RR) and risk difference (RD) based on different walking speeds. The researchers rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively.

Of the 508,121 potential participants, 18,410 adults from 10 prospective cohort studies conducted in the United States, Japan, and the United Kingdom were deemed eligible. The proportion of women was between 52% and 73%, depending on the cohort. Follow-up duration varied from 3 to 11.1 years (median, 8 years).

Five cohort studies measured walking speed using stopwatch testing, while the other five used self-assessed questionnaires. To define cases of T2D, seven studies used objective methods such as blood glucose measurement or linkage with medical records, and in three cohorts, self-assessment questionnaires were used (these were checked against patient records). All studies controlled age, sex, and tobacco consumption in the multivariate analyses, and some controlled just alcohol consumption, blood pressure, total physical activity volume, body mass index, time spent walking or daily step count, and a family history of diabetes.

The Right Speed

The authors first categorized walking speed into four prespecified levels: Easy or casual (< 2 mph or 3.2 km/h), average or normal (2-3 mph or 3.2-4.8 km/h), fairly brisk (3-4 mph or 4.8-6.4 km/h), and very brisk or brisk/striding (> 4 mph or > 6.4 km/h).

Four cohort studies with 6,520 cases of T2D among 160,321 participants reported information on average or normal walking. Participants with average or normal walking were at a 15% lower risk for T2D than those with easy or casual walking (RR = 0.85 [95% CI, 0.70-1.00]; RD = 0.86 [1.72-0]). Ten cohort studies with 18,410 cases among 508,121 participants reported information on fairly brisk walking. Those with fairly brisk walking were at a 24% lower risk for T2D than those with easy or casual walking (RR = 0.76 [0.65-0.87]; I2 = 90%; RD = 1.38 [2.01-0.75]).

There was no significant or credible subgroup difference by adjustment for the total physical activity or time spent walking per day. The dose-response analysis suggested that the risk for T2D decreased significantly at a walking speed of 4 km/h and above.

Study Limitations

This meta-analysis has strengths that may increase the generalizability of its results. The researchers included cohort studies, which allowed them to consider the temporal sequence of exposure and outcome. Cohort studies are less affected by recall and selection biases compared with retrospective case–control studies, which increase the likelihood of causality. The researchers also assessed the credibility of subgroup differences using the recently developed ICEMAN tool, calculated both relative and absolute risks, and rated the certainty of evidence using the GRADE approach.

Some shortcomings must be considered. Most of the studies included in the present review were rated as having a serious risk for bias, with the most important biases resulting from inadequate adjustment for potential confounders and the methods used for walking speed assessment and diagnosis of T2D. In addition, the findings could have been subject to reverse causality bias because participants with faster walking speed are more likely to perform more physical activity and have better cardiorespiratory fitness, greater muscle mass, and better health status. However, the subgroup analyses of fairly brisk and brisk/striding walking indicated that there were no significant subgroup differences by follow-up duration and that the significant inverse associations remained stable in the subgroup of cohort studies with a follow-up duration of > 10 years.

The authors concluded that “the present meta-analysis of cohort studies suggested that fairly brisk and brisk/striding walking, independent of the total volume of physical activity or time spent walking per day, may be associated with a lower risk of T2D in adults. While current strategies to increase total walking time are beneficial, it may also be reasonable to encourage people to walk at faster speeds to further increase the health benefits of walking.”

This article was translated from JIM, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Walking is a simple, cost-free form of exercise that benefits physical, social, and mental health in many ways. Several clinical trials have shown that walking regularly is associated with a lower risk for cardiovascular events and all-cause mortality, and having a higher daily step count is linked to a decreased risk for premature death.

Walking and Diabetes

In recent years, the link between walking speed and the risk for multiple health problems has sparked keen interest. Data suggest that a faster walking pace may have a greater physiological response and may be associated with more favorable health advantages than a slow walking pace. A previous meta-analysis of eight cohort studies suggested that individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk for stroke than those in the slowest walking-pace category (median = 1.6 km/h). The risk for the former decreased by 13% for every 1 km/h increment in baseline walking pace.

Type 2 diabetes (T2D) is one of the most common metabolic diseases in the world. People with this type of diabetes have an increased risk for microvascular and macrovascular complications and a shorter life expectancy. Approximately 537 million adults are estimated to be living with diabetes worldwide, and this number is expected to reach 783 million by 2045.

Physical activity is an essential component of T2D prevention programs and can favorably affect blood sugar control. A meta-analysis of cohort studies showed that being physically active was associated with a 35% reduction in the risk of acquiring T2D in the general population, and regular walking was associated with a 15% reduction in the risk of developing T2D.

However, no studies have investigated the link between different walking speeds and the risk for T2D. A team from the Research Center at the Semnan University of Medical Sciences in Iran carried out a systematic review of the association between walking speed and the risk of developing T2D in adults; this review was published in the British Journal of Sports Medicine.
 

10 Cohort Studies

This systematic review used publications (1999-2022) available in the usual data sources (PubMed, Scopus, CENTRAL, and Web of Science). Random-effects meta-analyses were used to calculate relative risk (RR) and risk difference (RD) based on different walking speeds. The researchers rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively.

Of the 508,121 potential participants, 18,410 adults from 10 prospective cohort studies conducted in the United States, Japan, and the United Kingdom were deemed eligible. The proportion of women was between 52% and 73%, depending on the cohort. Follow-up duration varied from 3 to 11.1 years (median, 8 years).

Five cohort studies measured walking speed using stopwatch testing, while the other five used self-assessed questionnaires. To define cases of T2D, seven studies used objective methods such as blood glucose measurement or linkage with medical records, and in three cohorts, self-assessment questionnaires were used (these were checked against patient records). All studies controlled age, sex, and tobacco consumption in the multivariate analyses, and some controlled just alcohol consumption, blood pressure, total physical activity volume, body mass index, time spent walking or daily step count, and a family history of diabetes.

The Right Speed

The authors first categorized walking speed into four prespecified levels: Easy or casual (< 2 mph or 3.2 km/h), average or normal (2-3 mph or 3.2-4.8 km/h), fairly brisk (3-4 mph or 4.8-6.4 km/h), and very brisk or brisk/striding (> 4 mph or > 6.4 km/h).

Four cohort studies with 6,520 cases of T2D among 160,321 participants reported information on average or normal walking. Participants with average or normal walking were at a 15% lower risk for T2D than those with easy or casual walking (RR = 0.85 [95% CI, 0.70-1.00]; RD = 0.86 [1.72-0]). Ten cohort studies with 18,410 cases among 508,121 participants reported information on fairly brisk walking. Those with fairly brisk walking were at a 24% lower risk for T2D than those with easy or casual walking (RR = 0.76 [0.65-0.87]; I2 = 90%; RD = 1.38 [2.01-0.75]).

There was no significant or credible subgroup difference by adjustment for the total physical activity or time spent walking per day. The dose-response analysis suggested that the risk for T2D decreased significantly at a walking speed of 4 km/h and above.

Study Limitations

This meta-analysis has strengths that may increase the generalizability of its results. The researchers included cohort studies, which allowed them to consider the temporal sequence of exposure and outcome. Cohort studies are less affected by recall and selection biases compared with retrospective case–control studies, which increase the likelihood of causality. The researchers also assessed the credibility of subgroup differences using the recently developed ICEMAN tool, calculated both relative and absolute risks, and rated the certainty of evidence using the GRADE approach.

Some shortcomings must be considered. Most of the studies included in the present review were rated as having a serious risk for bias, with the most important biases resulting from inadequate adjustment for potential confounders and the methods used for walking speed assessment and diagnosis of T2D. In addition, the findings could have been subject to reverse causality bias because participants with faster walking speed are more likely to perform more physical activity and have better cardiorespiratory fitness, greater muscle mass, and better health status. However, the subgroup analyses of fairly brisk and brisk/striding walking indicated that there were no significant subgroup differences by follow-up duration and that the significant inverse associations remained stable in the subgroup of cohort studies with a follow-up duration of > 10 years.

The authors concluded that “the present meta-analysis of cohort studies suggested that fairly brisk and brisk/striding walking, independent of the total volume of physical activity or time spent walking per day, may be associated with a lower risk of T2D in adults. While current strategies to increase total walking time are beneficial, it may also be reasonable to encourage people to walk at faster speeds to further increase the health benefits of walking.”

This article was translated from JIM, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Walking is a simple, cost-free form of exercise that benefits physical, social, and mental health in many ways. Several clinical trials have shown that walking regularly is associated with a lower risk for cardiovascular events and all-cause mortality, and having a higher daily step count is linked to a decreased risk for premature death.

Walking and Diabetes

In recent years, the link between walking speed and the risk for multiple health problems has sparked keen interest. Data suggest that a faster walking pace may have a greater physiological response and may be associated with more favorable health advantages than a slow walking pace. A previous meta-analysis of eight cohort studies suggested that individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk for stroke than those in the slowest walking-pace category (median = 1.6 km/h). The risk for the former decreased by 13% for every 1 km/h increment in baseline walking pace.

Type 2 diabetes (T2D) is one of the most common metabolic diseases in the world. People with this type of diabetes have an increased risk for microvascular and macrovascular complications and a shorter life expectancy. Approximately 537 million adults are estimated to be living with diabetes worldwide, and this number is expected to reach 783 million by 2045.

Physical activity is an essential component of T2D prevention programs and can favorably affect blood sugar control. A meta-analysis of cohort studies showed that being physically active was associated with a 35% reduction in the risk of acquiring T2D in the general population, and regular walking was associated with a 15% reduction in the risk of developing T2D.

However, no studies have investigated the link between different walking speeds and the risk for T2D. A team from the Research Center at the Semnan University of Medical Sciences in Iran carried out a systematic review of the association between walking speed and the risk of developing T2D in adults; this review was published in the British Journal of Sports Medicine.
 

10 Cohort Studies

This systematic review used publications (1999-2022) available in the usual data sources (PubMed, Scopus, CENTRAL, and Web of Science). Random-effects meta-analyses were used to calculate relative risk (RR) and risk difference (RD) based on different walking speeds. The researchers rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively.

Of the 508,121 potential participants, 18,410 adults from 10 prospective cohort studies conducted in the United States, Japan, and the United Kingdom were deemed eligible. The proportion of women was between 52% and 73%, depending on the cohort. Follow-up duration varied from 3 to 11.1 years (median, 8 years).

Five cohort studies measured walking speed using stopwatch testing, while the other five used self-assessed questionnaires. To define cases of T2D, seven studies used objective methods such as blood glucose measurement or linkage with medical records, and in three cohorts, self-assessment questionnaires were used (these were checked against patient records). All studies controlled age, sex, and tobacco consumption in the multivariate analyses, and some controlled just alcohol consumption, blood pressure, total physical activity volume, body mass index, time spent walking or daily step count, and a family history of diabetes.

The Right Speed

The authors first categorized walking speed into four prespecified levels: Easy or casual (< 2 mph or 3.2 km/h), average or normal (2-3 mph or 3.2-4.8 km/h), fairly brisk (3-4 mph or 4.8-6.4 km/h), and very brisk or brisk/striding (> 4 mph or > 6.4 km/h).

Four cohort studies with 6,520 cases of T2D among 160,321 participants reported information on average or normal walking. Participants with average or normal walking were at a 15% lower risk for T2D than those with easy or casual walking (RR = 0.85 [95% CI, 0.70-1.00]; RD = 0.86 [1.72-0]). Ten cohort studies with 18,410 cases among 508,121 participants reported information on fairly brisk walking. Those with fairly brisk walking were at a 24% lower risk for T2D than those with easy or casual walking (RR = 0.76 [0.65-0.87]; I2 = 90%; RD = 1.38 [2.01-0.75]).

There was no significant or credible subgroup difference by adjustment for the total physical activity or time spent walking per day. The dose-response analysis suggested that the risk for T2D decreased significantly at a walking speed of 4 km/h and above.

Study Limitations

This meta-analysis has strengths that may increase the generalizability of its results. The researchers included cohort studies, which allowed them to consider the temporal sequence of exposure and outcome. Cohort studies are less affected by recall and selection biases compared with retrospective case–control studies, which increase the likelihood of causality. The researchers also assessed the credibility of subgroup differences using the recently developed ICEMAN tool, calculated both relative and absolute risks, and rated the certainty of evidence using the GRADE approach.

Some shortcomings must be considered. Most of the studies included in the present review were rated as having a serious risk for bias, with the most important biases resulting from inadequate adjustment for potential confounders and the methods used for walking speed assessment and diagnosis of T2D. In addition, the findings could have been subject to reverse causality bias because participants with faster walking speed are more likely to perform more physical activity and have better cardiorespiratory fitness, greater muscle mass, and better health status. However, the subgroup analyses of fairly brisk and brisk/striding walking indicated that there were no significant subgroup differences by follow-up duration and that the significant inverse associations remained stable in the subgroup of cohort studies with a follow-up duration of > 10 years.

The authors concluded that “the present meta-analysis of cohort studies suggested that fairly brisk and brisk/striding walking, independent of the total volume of physical activity or time spent walking per day, may be associated with a lower risk of T2D in adults. While current strategies to increase total walking time are beneficial, it may also be reasonable to encourage people to walk at faster speeds to further increase the health benefits of walking.”

This article was translated from JIM, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has issued a warning to the public about counterfeit semaglutide (Ozempic) products that have entered the US drug supply. 

Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement. 

Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton. 

“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says. 

Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.” 

There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product. 

Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.

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

The US Food and Drug Administration (FDA) has issued a warning to the public about counterfeit semaglutide (Ozempic) products that have entered the US drug supply. 

Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement. 

Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton. 

“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says. 

Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.” 

There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product. 

Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.

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

The US Food and Drug Administration (FDA) has issued a warning to the public about counterfeit semaglutide (Ozempic) products that have entered the US drug supply. 

Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement. 

Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton. 

“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says. 

Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.” 

There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product. 

Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.

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

As we begin to find our way in the new world of obesity management, questions continue to surface more quickly than answers. This isn’t surprising, as we are being asked to view obesity as a disease when for decades the general consensus has been that overweight people are simply will power deficient.

Are the new drugs as effective as we are told by the patients and physicians who have had some experience using and prescribing them? Will they continue to be effective in the very long run? Will their safety record hold up over time? And for those of us in pediatrics, what will be their role for children? As a group we tend to be cautious about drugs that haven’t been thoroughly tested in children. How many years will it take before we feel comfortable with obesity drugs? And, of course, we should be asking ourselves the same questions about bariatric surgery.

Fortunately, while the media spotlight has been focused on the treatment arm of our obesity strategy, there are still some folks looking at what has been up to now the discouraging prospects for prevention. The U.S. Preventive Services Task Force (USPSTF) has recently released a draft of its recommendations that includes evidence supporting the effectiveness of “intensive behavioral interventions” (defined as a minimum of 26 hours of counseling). In reviewing data from nearly 60 randomized controlled trials, which included more than 10,000 children, the task force found that when beginning as early as age 6, a package including healthy eating education, physical activity, and behavioral change support could be effective in helping the children achieve healthy weight and an improved quality of life. It should be noted that the USPSTF gave the intervention package only a B grade, which means that the agency found evidence of high certainty of a moderate benefit over an unspecified time period. Certainly, not a ringing endorsement.

While I think we must applaud the diligent efforts of the task force and its commitment to prevention, I fear that the strategy is too little too late. That being said, I am willing to accept the idea that targeting age 6 for intensive counseling may qualify for the better-late-than-never category. The task force acknowledges that procuring the resources given our already understaffed mental health clinics is going to be difficult and expensive. I would add that it will be so costly in time and money as to be unrealistic.

Based on my observations of thousands of children, the scaffolding of habits, diet, and preference for inactivity that underly obesity has already been laid by age 6. Are we prepared to shoulder our already overburdened school systems in an attempt to reconfigure this foundation of an obesogenic lifestyle? An effort on this scale after children have been sent off to first grade is doomed to failure.

A recent review of data reported by the CDC and reviewed in the journal Pediatrics reveals that about 2% of children receiving federal assistance from the WIC program are severely obese. It is probably safe to say that these preschoolers represent just the tip of a very concerning iceberg.

By waiting until age 6, we would increase the risk of further stigmatizing the obese child. What will he tell his peers when he is taken out of school or misses a playdate because he has to meet with his “obesity counselor”?

If we are going to take obesity prevention seriously and spend time and money in counseling, doesn’t it make more sense to invest this effort on the parents and the home situation when the child is still under their influence? We must be prepared to unwrap and employ an “intensive behavioral package” the first time we see evidence that the child’s growth chart is heading in an unhealthy direction.

This won’t always be easy. I can recall seeing a 4-year-old whose weight had risen dramatically from her previous curve in the year since her 3-year checkup. The answer became obvious when I discovered that her grandmother, for whom baking was a passion, had taken over as her daycare provider. Arriving at a solution that kept the family on speaking terms took some tact, but it was one of my rare successes in obesity prevention. And, it worked because of early intervention.

Thank you USPSTF, but 6 years is too late.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As we begin to find our way in the new world of obesity management, questions continue to surface more quickly than answers. This isn’t surprising, as we are being asked to view obesity as a disease when for decades the general consensus has been that overweight people are simply will power deficient.

Are the new drugs as effective as we are told by the patients and physicians who have had some experience using and prescribing them? Will they continue to be effective in the very long run? Will their safety record hold up over time? And for those of us in pediatrics, what will be their role for children? As a group we tend to be cautious about drugs that haven’t been thoroughly tested in children. How many years will it take before we feel comfortable with obesity drugs? And, of course, we should be asking ourselves the same questions about bariatric surgery.

Fortunately, while the media spotlight has been focused on the treatment arm of our obesity strategy, there are still some folks looking at what has been up to now the discouraging prospects for prevention. The U.S. Preventive Services Task Force (USPSTF) has recently released a draft of its recommendations that includes evidence supporting the effectiveness of “intensive behavioral interventions” (defined as a minimum of 26 hours of counseling). In reviewing data from nearly 60 randomized controlled trials, which included more than 10,000 children, the task force found that when beginning as early as age 6, a package including healthy eating education, physical activity, and behavioral change support could be effective in helping the children achieve healthy weight and an improved quality of life. It should be noted that the USPSTF gave the intervention package only a B grade, which means that the agency found evidence of high certainty of a moderate benefit over an unspecified time period. Certainly, not a ringing endorsement.

While I think we must applaud the diligent efforts of the task force and its commitment to prevention, I fear that the strategy is too little too late. That being said, I am willing to accept the idea that targeting age 6 for intensive counseling may qualify for the better-late-than-never category. The task force acknowledges that procuring the resources given our already understaffed mental health clinics is going to be difficult and expensive. I would add that it will be so costly in time and money as to be unrealistic.

Based on my observations of thousands of children, the scaffolding of habits, diet, and preference for inactivity that underly obesity has already been laid by age 6. Are we prepared to shoulder our already overburdened school systems in an attempt to reconfigure this foundation of an obesogenic lifestyle? An effort on this scale after children have been sent off to first grade is doomed to failure.

A recent review of data reported by the CDC and reviewed in the journal Pediatrics reveals that about 2% of children receiving federal assistance from the WIC program are severely obese. It is probably safe to say that these preschoolers represent just the tip of a very concerning iceberg.

By waiting until age 6, we would increase the risk of further stigmatizing the obese child. What will he tell his peers when he is taken out of school or misses a playdate because he has to meet with his “obesity counselor”?

If we are going to take obesity prevention seriously and spend time and money in counseling, doesn’t it make more sense to invest this effort on the parents and the home situation when the child is still under their influence? We must be prepared to unwrap and employ an “intensive behavioral package” the first time we see evidence that the child’s growth chart is heading in an unhealthy direction.

This won’t always be easy. I can recall seeing a 4-year-old whose weight had risen dramatically from her previous curve in the year since her 3-year checkup. The answer became obvious when I discovered that her grandmother, for whom baking was a passion, had taken over as her daycare provider. Arriving at a solution that kept the family on speaking terms took some tact, but it was one of my rare successes in obesity prevention. And, it worked because of early intervention.

Thank you USPSTF, but 6 years is too late.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As we begin to find our way in the new world of obesity management, questions continue to surface more quickly than answers. This isn’t surprising, as we are being asked to view obesity as a disease when for decades the general consensus has been that overweight people are simply will power deficient.

Are the new drugs as effective as we are told by the patients and physicians who have had some experience using and prescribing them? Will they continue to be effective in the very long run? Will their safety record hold up over time? And for those of us in pediatrics, what will be their role for children? As a group we tend to be cautious about drugs that haven’t been thoroughly tested in children. How many years will it take before we feel comfortable with obesity drugs? And, of course, we should be asking ourselves the same questions about bariatric surgery.

Fortunately, while the media spotlight has been focused on the treatment arm of our obesity strategy, there are still some folks looking at what has been up to now the discouraging prospects for prevention. The U.S. Preventive Services Task Force (USPSTF) has recently released a draft of its recommendations that includes evidence supporting the effectiveness of “intensive behavioral interventions” (defined as a minimum of 26 hours of counseling). In reviewing data from nearly 60 randomized controlled trials, which included more than 10,000 children, the task force found that when beginning as early as age 6, a package including healthy eating education, physical activity, and behavioral change support could be effective in helping the children achieve healthy weight and an improved quality of life. It should be noted that the USPSTF gave the intervention package only a B grade, which means that the agency found evidence of high certainty of a moderate benefit over an unspecified time period. Certainly, not a ringing endorsement.

While I think we must applaud the diligent efforts of the task force and its commitment to prevention, I fear that the strategy is too little too late. That being said, I am willing to accept the idea that targeting age 6 for intensive counseling may qualify for the better-late-than-never category. The task force acknowledges that procuring the resources given our already understaffed mental health clinics is going to be difficult and expensive. I would add that it will be so costly in time and money as to be unrealistic.

Based on my observations of thousands of children, the scaffolding of habits, diet, and preference for inactivity that underly obesity has already been laid by age 6. Are we prepared to shoulder our already overburdened school systems in an attempt to reconfigure this foundation of an obesogenic lifestyle? An effort on this scale after children have been sent off to first grade is doomed to failure.

A recent review of data reported by the CDC and reviewed in the journal Pediatrics reveals that about 2% of children receiving federal assistance from the WIC program are severely obese. It is probably safe to say that these preschoolers represent just the tip of a very concerning iceberg.

By waiting until age 6, we would increase the risk of further stigmatizing the obese child. What will he tell his peers when he is taken out of school or misses a playdate because he has to meet with his “obesity counselor”?

If we are going to take obesity prevention seriously and spend time and money in counseling, doesn’t it make more sense to invest this effort on the parents and the home situation when the child is still under their influence? We must be prepared to unwrap and employ an “intensive behavioral package” the first time we see evidence that the child’s growth chart is heading in an unhealthy direction.

This won’t always be easy. I can recall seeing a 4-year-old whose weight had risen dramatically from her previous curve in the year since her 3-year checkup. The answer became obvious when I discovered that her grandmother, for whom baking was a passion, had taken over as her daycare provider. Arriving at a solution that kept the family on speaking terms took some tact, but it was one of my rare successes in obesity prevention. And, it worked because of early intervention.

Thank you USPSTF, but 6 years is too late.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].