When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.

Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.

Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.

In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.

The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.

They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.

The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.

“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.

More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.

“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.

The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.

Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.

Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.

Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.

In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.

The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.

They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.

The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.

“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.

More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.

“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.

The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.

Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.

Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.

Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.

In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.

The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.

They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.

The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.

“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.

More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.

“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.

The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.

LAS VEGAS – Although the range of oral psoriasis therapies continues to expand, “topical therapy is still the cornerstone of the treatment of psoriasis,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.

petekarici/Getty Images

Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.

The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.

In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.

Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
 

Get proactive to maintain results

With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.

Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,

She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.

What’s new and approved

Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.

Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.

In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.

Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.

Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.

Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.

Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

LAS VEGAS – Although the range of oral psoriasis therapies continues to expand, “topical therapy is still the cornerstone of the treatment of psoriasis,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.

petekarici/Getty Images

Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.

The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.

In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.

Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
 

Get proactive to maintain results

With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.

Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,

She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.

What’s new and approved

Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.

Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.

In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.

Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.

Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.

Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.

Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

LAS VEGAS – Although the range of oral psoriasis therapies continues to expand, “topical therapy is still the cornerstone of the treatment of psoriasis,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.

petekarici/Getty Images

Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.

The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.

In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.

Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
 

Get proactive to maintain results

With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.

Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,

She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.

What’s new and approved

Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.

Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.

In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.

Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.

Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.

Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.

Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

Two conservative interventions are effective for treating acute and subacute spine pain, new research suggests.

Results from the SPINE CARE randomized controlled trial showed that 6-8 weeks of an individualized postural therapy (IPT) or a multidisciplinary biopsychosocial intervention known as ICE (identify, coordinate, and enhance) that includes physical therapy were associated with small but statistically significant reductions in pain-related disability at 3 months compared with usual care.

In addition, spine-related health care spending did not differ significantly between ICE and usual care. However, IPT significantly increased spending compared with usual care.

“We found that, compared to usual primary care, both interventions reduced pain-related disability at 3 months and that these changes were sustained and clinically meaningful at 12 months – long after the interventions were over,” lead author Niteesh K. Choudhry, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, told this news organization.

The findings were published online in JAMA.
 

Common complaint

Spine pain is defined as pain that occurs in the neck or back, the investigators noted. It “accounted for more health spending than any other health condition in the U.S. in 2016,” they added.

“Spine pain is an exceptionally common reason for patients to visit their primary care providers,” Dr. Choudhry said.

The SPINE CARE trial enrolled 2,971 adults (60% were women; mean age was 51 years) with back or neck pain that had lasted less than 12 weeks. All were randomly allocated to usual care (no intervention, n = 992) or to the ICE (n = 829) or IPT (n = 1150) interventions.

The ICE care model stratifies patients on the basis of their risk of progression from acute to chronic pain and addresses biopsychosocial contributors to pain. Low-risk patients received one physical therapy (PT) visit and one coaching call, while higher-risk patients received three PT visits, three coaching calls, and one e-consultation.

The IPT intervention, which was delivered in 8 weekly sessions, focuses on postural realignment. IPT also emphasizes self-efficacy and self-management, including daily exercises to improve postural control, coordination, and muscle balance.

Results at 3 months showed that both the ICE and IPT groups improved significantly more in Oswestry Disability Index (ODI) scores than in the usual care group (ICE, 31.2 to 15.4; IPT, 29.3 to 15.4; usual care, 28.9 to 19.5).

At 3 months, the absolute difference in ODI score vs. usual care was −5.8 for ICE (95% confidence interval [CI], −7.7 to −3.9; P < .001) and −4.3 for IPT (95% CI, −5.9 to −2.6; P < .001) for IPT.

Both interventions reduced resource utilization, such as diagnostic imaging, procedures, and specialist visits, Dr. Choudhry reported. “Because of this, both reduced spending unrelated to the interventions themselves,” he added.

When the intervention costs were included, ICE resulted in lower costs overall than those of usual care ($139 less), while overall spending for IPT was higher than for usual care (by $941).

“We tested the interventions in a way that was integrated into primary care, so implementing them in other practice settings should be quite straightforward,” Dr. Choudhry said.

He noted that the ICE model does not currently exist as a complete program – but its components, such as physical therapy or specialist e-consults, do. “And we think that our results justify exploring how to set this up more broadly,” he said.

Dr. Choudhry added that IPT was tested using a specific provider (Egoscue), “which has locations in a variety of places in the U.S. and internationally, and so should also be straightforward to integrate into routine practice.”

However, other important factors, such as insurance coverage, will need to be explored in the future, he said.
 

Confirmatory evidence?

In an accompanying editorial, Erin Krebs, MD, Minneapolis VA Health Care System, and colleagues, noted that past systematic reviews have concluded that exercise therapies are “generally effective” for chronic back and neck pain, which is usually defined as pain lasting more than 12 weeks, but not for acute pain, defined as pain lasting less than 4-6 weeks.

“The present trial contributes evidence for effectiveness of exercise therapy among patients with a current episode of less than 12 weeks, meaning not yet chronic, but not necessarily acute,” the editorialists wrote.

“Clinicians should more often recommend structured exercise programs for subacute back or neck pain, especially when the pain is recurrent,” they added.

The study was funded by unrestricted philanthropic gifts to Stanford (Calif.) University. Dr. Choudhry received grants from Stanford University during the conduct of the study.

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

Two conservative interventions are effective for treating acute and subacute spine pain, new research suggests.

Results from the SPINE CARE randomized controlled trial showed that 6-8 weeks of an individualized postural therapy (IPT) or a multidisciplinary biopsychosocial intervention known as ICE (identify, coordinate, and enhance) that includes physical therapy were associated with small but statistically significant reductions in pain-related disability at 3 months compared with usual care.

In addition, spine-related health care spending did not differ significantly between ICE and usual care. However, IPT significantly increased spending compared with usual care.

“We found that, compared to usual primary care, both interventions reduced pain-related disability at 3 months and that these changes were sustained and clinically meaningful at 12 months – long after the interventions were over,” lead author Niteesh K. Choudhry, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, told this news organization.

The findings were published online in JAMA.
 

Common complaint

Spine pain is defined as pain that occurs in the neck or back, the investigators noted. It “accounted for more health spending than any other health condition in the U.S. in 2016,” they added.

“Spine pain is an exceptionally common reason for patients to visit their primary care providers,” Dr. Choudhry said.

The SPINE CARE trial enrolled 2,971 adults (60% were women; mean age was 51 years) with back or neck pain that had lasted less than 12 weeks. All were randomly allocated to usual care (no intervention, n = 992) or to the ICE (n = 829) or IPT (n = 1150) interventions.

The ICE care model stratifies patients on the basis of their risk of progression from acute to chronic pain and addresses biopsychosocial contributors to pain. Low-risk patients received one physical therapy (PT) visit and one coaching call, while higher-risk patients received three PT visits, three coaching calls, and one e-consultation.

The IPT intervention, which was delivered in 8 weekly sessions, focuses on postural realignment. IPT also emphasizes self-efficacy and self-management, including daily exercises to improve postural control, coordination, and muscle balance.

Results at 3 months showed that both the ICE and IPT groups improved significantly more in Oswestry Disability Index (ODI) scores than in the usual care group (ICE, 31.2 to 15.4; IPT, 29.3 to 15.4; usual care, 28.9 to 19.5).

At 3 months, the absolute difference in ODI score vs. usual care was −5.8 for ICE (95% confidence interval [CI], −7.7 to −3.9; P < .001) and −4.3 for IPT (95% CI, −5.9 to −2.6; P < .001) for IPT.

Both interventions reduced resource utilization, such as diagnostic imaging, procedures, and specialist visits, Dr. Choudhry reported. “Because of this, both reduced spending unrelated to the interventions themselves,” he added.

When the intervention costs were included, ICE resulted in lower costs overall than those of usual care ($139 less), while overall spending for IPT was higher than for usual care (by $941).

“We tested the interventions in a way that was integrated into primary care, so implementing them in other practice settings should be quite straightforward,” Dr. Choudhry said.

He noted that the ICE model does not currently exist as a complete program – but its components, such as physical therapy or specialist e-consults, do. “And we think that our results justify exploring how to set this up more broadly,” he said.

Dr. Choudhry added that IPT was tested using a specific provider (Egoscue), “which has locations in a variety of places in the U.S. and internationally, and so should also be straightforward to integrate into routine practice.”

However, other important factors, such as insurance coverage, will need to be explored in the future, he said.
 

Confirmatory evidence?

In an accompanying editorial, Erin Krebs, MD, Minneapolis VA Health Care System, and colleagues, noted that past systematic reviews have concluded that exercise therapies are “generally effective” for chronic back and neck pain, which is usually defined as pain lasting more than 12 weeks, but not for acute pain, defined as pain lasting less than 4-6 weeks.

“The present trial contributes evidence for effectiveness of exercise therapy among patients with a current episode of less than 12 weeks, meaning not yet chronic, but not necessarily acute,” the editorialists wrote.

“Clinicians should more often recommend structured exercise programs for subacute back or neck pain, especially when the pain is recurrent,” they added.

The study was funded by unrestricted philanthropic gifts to Stanford (Calif.) University. Dr. Choudhry received grants from Stanford University during the conduct of the study.

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

Two conservative interventions are effective for treating acute and subacute spine pain, new research suggests.

Results from the SPINE CARE randomized controlled trial showed that 6-8 weeks of an individualized postural therapy (IPT) or a multidisciplinary biopsychosocial intervention known as ICE (identify, coordinate, and enhance) that includes physical therapy were associated with small but statistically significant reductions in pain-related disability at 3 months compared with usual care.

In addition, spine-related health care spending did not differ significantly between ICE and usual care. However, IPT significantly increased spending compared with usual care.

“We found that, compared to usual primary care, both interventions reduced pain-related disability at 3 months and that these changes were sustained and clinically meaningful at 12 months – long after the interventions were over,” lead author Niteesh K. Choudhry, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, told this news organization.

The findings were published online in JAMA.
 

Common complaint

Spine pain is defined as pain that occurs in the neck or back, the investigators noted. It “accounted for more health spending than any other health condition in the U.S. in 2016,” they added.

“Spine pain is an exceptionally common reason for patients to visit their primary care providers,” Dr. Choudhry said.

The SPINE CARE trial enrolled 2,971 adults (60% were women; mean age was 51 years) with back or neck pain that had lasted less than 12 weeks. All were randomly allocated to usual care (no intervention, n = 992) or to the ICE (n = 829) or IPT (n = 1150) interventions.

The ICE care model stratifies patients on the basis of their risk of progression from acute to chronic pain and addresses biopsychosocial contributors to pain. Low-risk patients received one physical therapy (PT) visit and one coaching call, while higher-risk patients received three PT visits, three coaching calls, and one e-consultation.

The IPT intervention, which was delivered in 8 weekly sessions, focuses on postural realignment. IPT also emphasizes self-efficacy and self-management, including daily exercises to improve postural control, coordination, and muscle balance.

Results at 3 months showed that both the ICE and IPT groups improved significantly more in Oswestry Disability Index (ODI) scores than in the usual care group (ICE, 31.2 to 15.4; IPT, 29.3 to 15.4; usual care, 28.9 to 19.5).

At 3 months, the absolute difference in ODI score vs. usual care was −5.8 for ICE (95% confidence interval [CI], −7.7 to −3.9; P < .001) and −4.3 for IPT (95% CI, −5.9 to −2.6; P < .001) for IPT.

Both interventions reduced resource utilization, such as diagnostic imaging, procedures, and specialist visits, Dr. Choudhry reported. “Because of this, both reduced spending unrelated to the interventions themselves,” he added.

When the intervention costs were included, ICE resulted in lower costs overall than those of usual care ($139 less), while overall spending for IPT was higher than for usual care (by $941).

“We tested the interventions in a way that was integrated into primary care, so implementing them in other practice settings should be quite straightforward,” Dr. Choudhry said.

He noted that the ICE model does not currently exist as a complete program – but its components, such as physical therapy or specialist e-consults, do. “And we think that our results justify exploring how to set this up more broadly,” he said.

Dr. Choudhry added that IPT was tested using a specific provider (Egoscue), “which has locations in a variety of places in the U.S. and internationally, and so should also be straightforward to integrate into routine practice.”

However, other important factors, such as insurance coverage, will need to be explored in the future, he said.
 

Confirmatory evidence?

In an accompanying editorial, Erin Krebs, MD, Minneapolis VA Health Care System, and colleagues, noted that past systematic reviews have concluded that exercise therapies are “generally effective” for chronic back and neck pain, which is usually defined as pain lasting more than 12 weeks, but not for acute pain, defined as pain lasting less than 4-6 weeks.

“The present trial contributes evidence for effectiveness of exercise therapy among patients with a current episode of less than 12 weeks, meaning not yet chronic, but not necessarily acute,” the editorialists wrote.

“Clinicians should more often recommend structured exercise programs for subacute back or neck pain, especially when the pain is recurrent,” they added.

The study was funded by unrestricted philanthropic gifts to Stanford (Calif.) University. Dr. Choudhry received grants from Stanford University during the conduct of the study.

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

A recent study found that people with obesity have lower blood levels of vitamin D than people of healthy weight. This association of obesity with low vitamin D levels has led to much speculation on whether low vitamin D levels cause obesity or whether obesity causes low vitamin D levels. The interest in this topic is piqued by the possibility that if vitamin D deficiency causes obesity, perhaps treatment could be as simple as providing vitamin D supplementation to enhance weight loss.

What is known about vitamin D’s role in the body?

It’s well known that vitamin D is essential for bone health as well as balancing the minerals calcium and phosphorus, but what is its role in weight management? Approximately 80%-90% of vitamin D in the body is from the skin synthesis of cholecalciferol through ultraviolet B radiation from sun exposure. The normal range of 25-hydroxy vitamin D is measured as nanograms per milliliter (ng/mL). Most experts recommend a level between 20 and 40 ng/mL, but this has been a controversial topic of never-ending debate in the medical literature.

Vitamin D levels and obesity

A strong link exists between low vitamin D levels (serum 25[OH] vitamin D) and obesity. This has been noted for many years without identifying the underlying reasons beyond the sequestering of vitamin D in adipose tissue, although I’ll discuss other possibilities.

The inverse correlation between vitamin D and obesity has been seen in other diseases, such as cardiovascular disease, hypertension, prediabetes, and insulin resistance, as well as in sarcopenia and aging. Most studies emphasized the correlation between increasing adiposity with vitamin D deficiency in all ethnic and age groups. The causes and potential direct consequences of the vitamin D deficiency state in obesity are not well understood.
 

Vitamin D and adipose tissue

It’s been proposed that low vitamin D status in obesity might be due to increased vitamin D clearance from serum and enhanced storage of vitamin D by adipose tissue.

In adipose tissue, vitamin D exerts a variety of effects on inflammation, innate immunity, metabolism, and differentiation and apoptosis in many cell types. There is a stronger association between 25(OH)D and visceral fat as compared to subcutaneous adipose tissue, which suggests an influence of inflammation and components of the metabolic syndrome on vitamin D metabolism.

Because vitamin D has anti-inflammatory properties, it’s possible that low vitamin D status contributes to adipose tissue inflammation, a key link between obesity and its associated metabolic complications in obesity. A higher storage of vitamin D in adipose tissue, if accompanied by a parallel increase in the local synthesis of 1,25(OH)2D3 and action, may conceivably modulate adipocyte function as well as the activity of adipose tissue macrophages and hence the level of adipose tissue inflammation. In addition, it seems likely that 1,25(OH)2D3 also regulates the function of macrophages and other immune cell populations within adipose tissue.

It’s well known that vitamin D is stored in body fat, leading to the assumption that this was important in the evolution of vertebrates, including humans, who lived at latitudes where vitamin D could not be made in the winter and vitamin D stores had to be mobilized to maintain vitamin D sufficiency.
 

What is vitamin D’s role in obesity?

The main question that has eluded an answer so far is this one: Is vitamin D deficiency only a coincidental finding in obesity due to sequestration of the vitamin in fat, or does it have a role in the development of obesity and its complications, such as cardiovascular disease, type 2 diabetes, and hypertension?

Low vitamin D usually leads to impaired calcium absorption in the intestine and a lower calcium level, and eventually enhanced bone turnover and impaired bone mineral density (BMD).

However, it is known that in obesity there is greater BMD than in those who are lean. This leads to the conclusion that because there is a lack of vitamin D deficiency effects on bone in those with obesity, there is not really a vitamin D deficiency, and it may be that the sequestration in adipose tissue leads to a permanent supply that can maintain bone health.

An alternative explanation is that there is greater skeletal loading in obesity, and elevations in hormones such as estrogen and leptin could compensate for the vitamin D deficiency, leading to greater BMD in obesity.

Several other potential mechanisms besides sequestration of vitamin D in adipose tissue have been identified for low vitamin D and obesity. These include impaired hepatic 25-hydroxylation in nonalcoholic fatty liver disease, less sunlight exposure due to lower mobility and different clothing habits in people with obesity vs. their lean counterparts, and adverse dietary habits. For example, people with higher BMIs spend less time exercising outdoors and are more sedentary in general than their lean counterparts. Therefore, they are less likely to get sun exposure because of a decrease in time spent outdoors. Those with higher BMIs also tend to cover their bodies, showing less skin when outdoors than their leaner counterparts, and thus there is likely to be less conversion to vitamin D via skin and sun exposure in people with obesity.

Some studies suggest that an increased level of parathyroid hormone due to vitamin D deficiency promotes lipogenesis because of greater calcium influx in adipocytes. Another hypothesis is that the active form of vitamin D, 1,25(OH) D, inhibits adipogenesis through actions modulated by vitamin D receptors. These studies are promising, but prospective randomized trials are needed to determine whether vitamin D supplementation is a treatment option in preventing obesity. So far, vitamin D supplementation shows inconsistent results.

To conclude, there is a high prevalence of vitamin D deficiency in obesity, most likely because of dilution and sequestration in greater volumes of fat, blood muscle, and liver in obesity. Low vitamin D levels can’t be ruled out as a cause of obesity because of the research showing some interesting findings in vitamin D receptors in adipose tissue. Vitamin D deficiency in obesity doesn’t seem to affect bone mass but could have deleterious effects on other organ systems.

Weight loss improves obesity and complications, including the risk for cardiovascular disease and type 2 diabetes as well as vitamin D deficiency.
 

What do the guidelines say?

Treatment of vitamin D deficiency requires higher doses in obesity to achieve the same serum concentration compared with lean persons. Maintenance doses should not differ between those with obesity and lean persons.

The association of vitamin D and obesity remains elusive. Studies need to focus on vitamin D, vitamin D receptors, and actions of vitamin D in adipose tissue to investigate this relationship further.

In the meantime, media attention remains focused on the potential treatment and prevention of obesity with the mighty, all-purpose vitamin D, even though there is scant evidence.

Dr. Apovian is codirector at the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine in the division of endocrinology, diabetes and hypertension at Harvard University, Boston. She disclosed conflicts of interest with Abbott, Allergan, Altimmune, Bariatrix Nutrition, Cowen and Company, Curavit, Rhythm Pharma, Jazz, Nutrisystem, Roman, Novo Nordisk, EnteroMedics, Gelesis Srl, Zafgen, Xeno, L-Nutra, Tivity, and Real Appeal.

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

A recent study found that people with obesity have lower blood levels of vitamin D than people of healthy weight. This association of obesity with low vitamin D levels has led to much speculation on whether low vitamin D levels cause obesity or whether obesity causes low vitamin D levels. The interest in this topic is piqued by the possibility that if vitamin D deficiency causes obesity, perhaps treatment could be as simple as providing vitamin D supplementation to enhance weight loss.

What is known about vitamin D’s role in the body?

It’s well known that vitamin D is essential for bone health as well as balancing the minerals calcium and phosphorus, but what is its role in weight management? Approximately 80%-90% of vitamin D in the body is from the skin synthesis of cholecalciferol through ultraviolet B radiation from sun exposure. The normal range of 25-hydroxy vitamin D is measured as nanograms per milliliter (ng/mL). Most experts recommend a level between 20 and 40 ng/mL, but this has been a controversial topic of never-ending debate in the medical literature.

Vitamin D levels and obesity

A strong link exists between low vitamin D levels (serum 25[OH] vitamin D) and obesity. This has been noted for many years without identifying the underlying reasons beyond the sequestering of vitamin D in adipose tissue, although I’ll discuss other possibilities.

The inverse correlation between vitamin D and obesity has been seen in other diseases, such as cardiovascular disease, hypertension, prediabetes, and insulin resistance, as well as in sarcopenia and aging. Most studies emphasized the correlation between increasing adiposity with vitamin D deficiency in all ethnic and age groups. The causes and potential direct consequences of the vitamin D deficiency state in obesity are not well understood.
 

Vitamin D and adipose tissue

It’s been proposed that low vitamin D status in obesity might be due to increased vitamin D clearance from serum and enhanced storage of vitamin D by adipose tissue.

In adipose tissue, vitamin D exerts a variety of effects on inflammation, innate immunity, metabolism, and differentiation and apoptosis in many cell types. There is a stronger association between 25(OH)D and visceral fat as compared to subcutaneous adipose tissue, which suggests an influence of inflammation and components of the metabolic syndrome on vitamin D metabolism.

Because vitamin D has anti-inflammatory properties, it’s possible that low vitamin D status contributes to adipose tissue inflammation, a key link between obesity and its associated metabolic complications in obesity. A higher storage of vitamin D in adipose tissue, if accompanied by a parallel increase in the local synthesis of 1,25(OH)2D3 and action, may conceivably modulate adipocyte function as well as the activity of adipose tissue macrophages and hence the level of adipose tissue inflammation. In addition, it seems likely that 1,25(OH)2D3 also regulates the function of macrophages and other immune cell populations within adipose tissue.

It’s well known that vitamin D is stored in body fat, leading to the assumption that this was important in the evolution of vertebrates, including humans, who lived at latitudes where vitamin D could not be made in the winter and vitamin D stores had to be mobilized to maintain vitamin D sufficiency.
 

What is vitamin D’s role in obesity?

The main question that has eluded an answer so far is this one: Is vitamin D deficiency only a coincidental finding in obesity due to sequestration of the vitamin in fat, or does it have a role in the development of obesity and its complications, such as cardiovascular disease, type 2 diabetes, and hypertension?

Low vitamin D usually leads to impaired calcium absorption in the intestine and a lower calcium level, and eventually enhanced bone turnover and impaired bone mineral density (BMD).

However, it is known that in obesity there is greater BMD than in those who are lean. This leads to the conclusion that because there is a lack of vitamin D deficiency effects on bone in those with obesity, there is not really a vitamin D deficiency, and it may be that the sequestration in adipose tissue leads to a permanent supply that can maintain bone health.

An alternative explanation is that there is greater skeletal loading in obesity, and elevations in hormones such as estrogen and leptin could compensate for the vitamin D deficiency, leading to greater BMD in obesity.

Several other potential mechanisms besides sequestration of vitamin D in adipose tissue have been identified for low vitamin D and obesity. These include impaired hepatic 25-hydroxylation in nonalcoholic fatty liver disease, less sunlight exposure due to lower mobility and different clothing habits in people with obesity vs. their lean counterparts, and adverse dietary habits. For example, people with higher BMIs spend less time exercising outdoors and are more sedentary in general than their lean counterparts. Therefore, they are less likely to get sun exposure because of a decrease in time spent outdoors. Those with higher BMIs also tend to cover their bodies, showing less skin when outdoors than their leaner counterparts, and thus there is likely to be less conversion to vitamin D via skin and sun exposure in people with obesity.

Some studies suggest that an increased level of parathyroid hormone due to vitamin D deficiency promotes lipogenesis because of greater calcium influx in adipocytes. Another hypothesis is that the active form of vitamin D, 1,25(OH) D, inhibits adipogenesis through actions modulated by vitamin D receptors. These studies are promising, but prospective randomized trials are needed to determine whether vitamin D supplementation is a treatment option in preventing obesity. So far, vitamin D supplementation shows inconsistent results.

To conclude, there is a high prevalence of vitamin D deficiency in obesity, most likely because of dilution and sequestration in greater volumes of fat, blood muscle, and liver in obesity. Low vitamin D levels can’t be ruled out as a cause of obesity because of the research showing some interesting findings in vitamin D receptors in adipose tissue. Vitamin D deficiency in obesity doesn’t seem to affect bone mass but could have deleterious effects on other organ systems.

Weight loss improves obesity and complications, including the risk for cardiovascular disease and type 2 diabetes as well as vitamin D deficiency.
 

What do the guidelines say?

Treatment of vitamin D deficiency requires higher doses in obesity to achieve the same serum concentration compared with lean persons. Maintenance doses should not differ between those with obesity and lean persons.

The association of vitamin D and obesity remains elusive. Studies need to focus on vitamin D, vitamin D receptors, and actions of vitamin D in adipose tissue to investigate this relationship further.

In the meantime, media attention remains focused on the potential treatment and prevention of obesity with the mighty, all-purpose vitamin D, even though there is scant evidence.

Dr. Apovian is codirector at the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine in the division of endocrinology, diabetes and hypertension at Harvard University, Boston. She disclosed conflicts of interest with Abbott, Allergan, Altimmune, Bariatrix Nutrition, Cowen and Company, Curavit, Rhythm Pharma, Jazz, Nutrisystem, Roman, Novo Nordisk, EnteroMedics, Gelesis Srl, Zafgen, Xeno, L-Nutra, Tivity, and Real Appeal.

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

A recent study found that people with obesity have lower blood levels of vitamin D than people of healthy weight. This association of obesity with low vitamin D levels has led to much speculation on whether low vitamin D levels cause obesity or whether obesity causes low vitamin D levels. The interest in this topic is piqued by the possibility that if vitamin D deficiency causes obesity, perhaps treatment could be as simple as providing vitamin D supplementation to enhance weight loss.

What is known about vitamin D’s role in the body?

It’s well known that vitamin D is essential for bone health as well as balancing the minerals calcium and phosphorus, but what is its role in weight management? Approximately 80%-90% of vitamin D in the body is from the skin synthesis of cholecalciferol through ultraviolet B radiation from sun exposure. The normal range of 25-hydroxy vitamin D is measured as nanograms per milliliter (ng/mL). Most experts recommend a level between 20 and 40 ng/mL, but this has been a controversial topic of never-ending debate in the medical literature.

Vitamin D levels and obesity

A strong link exists between low vitamin D levels (serum 25[OH] vitamin D) and obesity. This has been noted for many years without identifying the underlying reasons beyond the sequestering of vitamin D in adipose tissue, although I’ll discuss other possibilities.

The inverse correlation between vitamin D and obesity has been seen in other diseases, such as cardiovascular disease, hypertension, prediabetes, and insulin resistance, as well as in sarcopenia and aging. Most studies emphasized the correlation between increasing adiposity with vitamin D deficiency in all ethnic and age groups. The causes and potential direct consequences of the vitamin D deficiency state in obesity are not well understood.
 

Vitamin D and adipose tissue

It’s been proposed that low vitamin D status in obesity might be due to increased vitamin D clearance from serum and enhanced storage of vitamin D by adipose tissue.

In adipose tissue, vitamin D exerts a variety of effects on inflammation, innate immunity, metabolism, and differentiation and apoptosis in many cell types. There is a stronger association between 25(OH)D and visceral fat as compared to subcutaneous adipose tissue, which suggests an influence of inflammation and components of the metabolic syndrome on vitamin D metabolism.

Because vitamin D has anti-inflammatory properties, it’s possible that low vitamin D status contributes to adipose tissue inflammation, a key link between obesity and its associated metabolic complications in obesity. A higher storage of vitamin D in adipose tissue, if accompanied by a parallel increase in the local synthesis of 1,25(OH)2D3 and action, may conceivably modulate adipocyte function as well as the activity of adipose tissue macrophages and hence the level of adipose tissue inflammation. In addition, it seems likely that 1,25(OH)2D3 also regulates the function of macrophages and other immune cell populations within adipose tissue.

It’s well known that vitamin D is stored in body fat, leading to the assumption that this was important in the evolution of vertebrates, including humans, who lived at latitudes where vitamin D could not be made in the winter and vitamin D stores had to be mobilized to maintain vitamin D sufficiency.
 

What is vitamin D’s role in obesity?

The main question that has eluded an answer so far is this one: Is vitamin D deficiency only a coincidental finding in obesity due to sequestration of the vitamin in fat, or does it have a role in the development of obesity and its complications, such as cardiovascular disease, type 2 diabetes, and hypertension?

Low vitamin D usually leads to impaired calcium absorption in the intestine and a lower calcium level, and eventually enhanced bone turnover and impaired bone mineral density (BMD).

However, it is known that in obesity there is greater BMD than in those who are lean. This leads to the conclusion that because there is a lack of vitamin D deficiency effects on bone in those with obesity, there is not really a vitamin D deficiency, and it may be that the sequestration in adipose tissue leads to a permanent supply that can maintain bone health.

An alternative explanation is that there is greater skeletal loading in obesity, and elevations in hormones such as estrogen and leptin could compensate for the vitamin D deficiency, leading to greater BMD in obesity.

Several other potential mechanisms besides sequestration of vitamin D in adipose tissue have been identified for low vitamin D and obesity. These include impaired hepatic 25-hydroxylation in nonalcoholic fatty liver disease, less sunlight exposure due to lower mobility and different clothing habits in people with obesity vs. their lean counterparts, and adverse dietary habits. For example, people with higher BMIs spend less time exercising outdoors and are more sedentary in general than their lean counterparts. Therefore, they are less likely to get sun exposure because of a decrease in time spent outdoors. Those with higher BMIs also tend to cover their bodies, showing less skin when outdoors than their leaner counterparts, and thus there is likely to be less conversion to vitamin D via skin and sun exposure in people with obesity.

Some studies suggest that an increased level of parathyroid hormone due to vitamin D deficiency promotes lipogenesis because of greater calcium influx in adipocytes. Another hypothesis is that the active form of vitamin D, 1,25(OH) D, inhibits adipogenesis through actions modulated by vitamin D receptors. These studies are promising, but prospective randomized trials are needed to determine whether vitamin D supplementation is a treatment option in preventing obesity. So far, vitamin D supplementation shows inconsistent results.

To conclude, there is a high prevalence of vitamin D deficiency in obesity, most likely because of dilution and sequestration in greater volumes of fat, blood muscle, and liver in obesity. Low vitamin D levels can’t be ruled out as a cause of obesity because of the research showing some interesting findings in vitamin D receptors in adipose tissue. Vitamin D deficiency in obesity doesn’t seem to affect bone mass but could have deleterious effects on other organ systems.

Weight loss improves obesity and complications, including the risk for cardiovascular disease and type 2 diabetes as well as vitamin D deficiency.
 

What do the guidelines say?

Treatment of vitamin D deficiency requires higher doses in obesity to achieve the same serum concentration compared with lean persons. Maintenance doses should not differ between those with obesity and lean persons.

The association of vitamin D and obesity remains elusive. Studies need to focus on vitamin D, vitamin D receptors, and actions of vitamin D in adipose tissue to investigate this relationship further.

In the meantime, media attention remains focused on the potential treatment and prevention of obesity with the mighty, all-purpose vitamin D, even though there is scant evidence.

Dr. Apovian is codirector at the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine in the division of endocrinology, diabetes and hypertension at Harvard University, Boston. She disclosed conflicts of interest with Abbott, Allergan, Altimmune, Bariatrix Nutrition, Cowen and Company, Curavit, Rhythm Pharma, Jazz, Nutrisystem, Roman, Novo Nordisk, EnteroMedics, Gelesis Srl, Zafgen, Xeno, L-Nutra, Tivity, and Real Appeal.

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

Lupin Pharmaceuticals is recalling four lots of quinapril tablets because of unacceptable levels of the nitrosamine impurity, N-nitroso-quinapril, a potential carcinogen.

Nitrosamines “may increase the risk of cancer if people are exposed to them above acceptable levels over long periods of time,” the company says in a recall notice posted on the Food and Drug Administration website.

Lupin says it “has received no reports of illness that appear to relate to this issue.”

Quinapril is an ACE inhibitor used to treat hypertension. Lupin stopped marketing quinapril tablets in September 2022.

The recalled product – quinapril tablets USP 20 mg and 40 mg – are packaged in 90-count bottles and were distributed nationwide to U.S. wholesalers, drug chains, mail order pharmacies, and supermarkets between March 15, 2021, and Sept. 1, 2022.

Lupin is notifying customers to immediately stop distribution of the recalled product and is arranging for the affected product lots to be returned to the company.

The company is advising patients to continue taking their medication and to contact their pharmacist, physician, or healthcare professional for advice regarding an alternative treatment.

Questions regarding this recall should be directed to Inmar Rx Solutions at (877) 538-8445 Monday to Friday between 9:00 a.m. to 5:00 p.m. EST.

Patients and physicians are also advised to report any adverse events or side effects related to the affected products to MedWatch, the FDA’s Safety Information and Adverse Event Reporting program.

Pfizer recalled several lots of quinapril owing to the presence of the same impurity in March 2022and again in April.

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

Lupin Pharmaceuticals is recalling four lots of quinapril tablets because of unacceptable levels of the nitrosamine impurity, N-nitroso-quinapril, a potential carcinogen.

Nitrosamines “may increase the risk of cancer if people are exposed to them above acceptable levels over long periods of time,” the company says in a recall notice posted on the Food and Drug Administration website.

Lupin says it “has received no reports of illness that appear to relate to this issue.”

Quinapril is an ACE inhibitor used to treat hypertension. Lupin stopped marketing quinapril tablets in September 2022.

The recalled product – quinapril tablets USP 20 mg and 40 mg – are packaged in 90-count bottles and were distributed nationwide to U.S. wholesalers, drug chains, mail order pharmacies, and supermarkets between March 15, 2021, and Sept. 1, 2022.

Lupin is notifying customers to immediately stop distribution of the recalled product and is arranging for the affected product lots to be returned to the company.

The company is advising patients to continue taking their medication and to contact their pharmacist, physician, or healthcare professional for advice regarding an alternative treatment.

Questions regarding this recall should be directed to Inmar Rx Solutions at (877) 538-8445 Monday to Friday between 9:00 a.m. to 5:00 p.m. EST.

Patients and physicians are also advised to report any adverse events or side effects related to the affected products to MedWatch, the FDA’s Safety Information and Adverse Event Reporting program.

Pfizer recalled several lots of quinapril owing to the presence of the same impurity in March 2022and again in April.

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

Lupin Pharmaceuticals is recalling four lots of quinapril tablets because of unacceptable levels of the nitrosamine impurity, N-nitroso-quinapril, a potential carcinogen.

Nitrosamines “may increase the risk of cancer if people are exposed to them above acceptable levels over long periods of time,” the company says in a recall notice posted on the Food and Drug Administration website.

Lupin says it “has received no reports of illness that appear to relate to this issue.”

Quinapril is an ACE inhibitor used to treat hypertension. Lupin stopped marketing quinapril tablets in September 2022.

The recalled product – quinapril tablets USP 20 mg and 40 mg – are packaged in 90-count bottles and were distributed nationwide to U.S. wholesalers, drug chains, mail order pharmacies, and supermarkets between March 15, 2021, and Sept. 1, 2022.

Lupin is notifying customers to immediately stop distribution of the recalled product and is arranging for the affected product lots to be returned to the company.

The company is advising patients to continue taking their medication and to contact their pharmacist, physician, or healthcare professional for advice regarding an alternative treatment.

Questions regarding this recall should be directed to Inmar Rx Solutions at (877) 538-8445 Monday to Friday between 9:00 a.m. to 5:00 p.m. EST.

Patients and physicians are also advised to report any adverse events or side effects related to the affected products to MedWatch, the FDA’s Safety Information and Adverse Event Reporting program.

Pfizer recalled several lots of quinapril owing to the presence of the same impurity in March 2022and again in April.

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

SAN DIEGO – In the clinical experience of Jeremy B. Green, MD, men typically require a higher dose of facial neuromodulators for nonsurgical wrinkle reduction compared with women because of anatomical differences.

“Men generally have larger facial muscle mass,” Dr. Green, a dermatologist in Coral Gables, Fla., said at the annual Masters of Aesthetics Symposium. “We need a higher dose to treat them, or they will not be happy. In general, I try to increase the dose by about 50% for my male patients.”

Two early trials of dose adjustments support this practice, he said. In one, 80 men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (Botox) in the glabellar area. The researchers found that the 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose.

In a subsequent study, researchers administered botulinum toxin type A (Dysport) 0.5 to 0.7 mL for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation at several time points up to 150 days post treatment. The median duration of effect was 109 days vs. 0 days for placebo in the blinded evaluator evaluation and 107 days vs. 0 for placebo in the patient self-evaluation.

Most injection algorithms for treating the glabella rely on a 5- or 7-point injection technique, but in 2021, researchers led by Sebastian Cotofana, MD, PhD, of the department of clinical anatomy at Mayo Clinic, Rochester, Minn., reported results from a study of the efficacy and safety of a refined 3-point injection technique targeting horizontal and vertical lines to prevent brow ptosis.

“Prior to this study Sebastian asked me, ‘Why do you guys always inject the body of the muscle?’ ” Dr. Green said. “‘If you inject the origin of the muscle on bone, you could more effectively wipe out the entire muscle’s movement. You’re going to get a better result at a lower dose, so let’s study this.’”

The injection technique involves targeting the midline level of the connecting line between left and right medial canthal ligaments with a 90-degree injection angle with bone contact, as well as the medial and inferior margin of eyebrows with a 45-degree injection angle in relation to midline with frontal bone contact. These three points are located inferior to the traditional (on-label) glabellar frown line injections used to treat the frontalis and the brow depressors.

The researchers used the 5-point glabellar line severity scale to evaluate the time of effect onset and the injection-related outcome 120 days after the treatment in 27 men and 78 women. They found that the onset of the neuromodulator effect occurred in an average of 3.5 days, and no adverse events such as eyebrow ptosis, upper eyelid ptosis, medial eyebrow ptosis, and lateral frontalis hyperactivity occurred during the study period.

“If you inject the origin of these muscles, you can get a brow lift with this technique by avoiding frontalis altogether,” Dr. Green said. “The caveat is, it’s so great at lifting the brows that if you treat the forehead, you may create a midline horizontal ‘shelf’ like I’ve never seen before, where the eyebrows elevate into an immobile superior frontalis.”

To avoid this when treating the forehead as well, he’s learned to split the dose of neuromodulator. “If I was injecting 5 units in the procerus before, I’ll do 2.5 units on nasal bone at the insertion of the muscle and then 2.5 units higher up in the traditional midline procerus injection site,” Dr. Green said.

“Same with the corrugators,” he continued. “Then, remember to inject more superficially in the lateral part, the tail of the corrugators, because the tail of the corrugators is inserting into the undersurface of the dermis. That’s why you see that skin puckering in the lateral brows when people frown. You’re pretty safe to chase that laterally if the brow’s already flat as in men, but I caution you [not] to do that in women, because you may flatten the brow.”

Dr. Green said that he is aware of two cases of lid ptosis from the 3-point technique, one of which happened to him.

“When you’re on the bone with your thumb you can feel that liquid traveling along the bone,” he said. “It can travel all the way to the midline pupil where the levator palpebrae superioris muscle is. I now don’t come in contact with bone with my corrugator origin injections, but rather float the needle a couple of millimeters off bone (in muscle) to hopefully prevent that from happening. Alternatively, some people will compress the brow along frontal bone lateral to that corrugator injection site while they’re injecting to prevent backflow of the neuromodulator.”

Dr. Green reported having received research funding and/or consulting fees from many device and pharmaceutical companies.

SAN DIEGO – In the clinical experience of Jeremy B. Green, MD, men typically require a higher dose of facial neuromodulators for nonsurgical wrinkle reduction compared with women because of anatomical differences.

“Men generally have larger facial muscle mass,” Dr. Green, a dermatologist in Coral Gables, Fla., said at the annual Masters of Aesthetics Symposium. “We need a higher dose to treat them, or they will not be happy. In general, I try to increase the dose by about 50% for my male patients.”

Two early trials of dose adjustments support this practice, he said. In one, 80 men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (Botox) in the glabellar area. The researchers found that the 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose.

In a subsequent study, researchers administered botulinum toxin type A (Dysport) 0.5 to 0.7 mL for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation at several time points up to 150 days post treatment. The median duration of effect was 109 days vs. 0 days for placebo in the blinded evaluator evaluation and 107 days vs. 0 for placebo in the patient self-evaluation.

Most injection algorithms for treating the glabella rely on a 5- or 7-point injection technique, but in 2021, researchers led by Sebastian Cotofana, MD, PhD, of the department of clinical anatomy at Mayo Clinic, Rochester, Minn., reported results from a study of the efficacy and safety of a refined 3-point injection technique targeting horizontal and vertical lines to prevent brow ptosis.

“Prior to this study Sebastian asked me, ‘Why do you guys always inject the body of the muscle?’ ” Dr. Green said. “‘If you inject the origin of the muscle on bone, you could more effectively wipe out the entire muscle’s movement. You’re going to get a better result at a lower dose, so let’s study this.’”

The injection technique involves targeting the midline level of the connecting line between left and right medial canthal ligaments with a 90-degree injection angle with bone contact, as well as the medial and inferior margin of eyebrows with a 45-degree injection angle in relation to midline with frontal bone contact. These three points are located inferior to the traditional (on-label) glabellar frown line injections used to treat the frontalis and the brow depressors.

The researchers used the 5-point glabellar line severity scale to evaluate the time of effect onset and the injection-related outcome 120 days after the treatment in 27 men and 78 women. They found that the onset of the neuromodulator effect occurred in an average of 3.5 days, and no adverse events such as eyebrow ptosis, upper eyelid ptosis, medial eyebrow ptosis, and lateral frontalis hyperactivity occurred during the study period.

“If you inject the origin of these muscles, you can get a brow lift with this technique by avoiding frontalis altogether,” Dr. Green said. “The caveat is, it’s so great at lifting the brows that if you treat the forehead, you may create a midline horizontal ‘shelf’ like I’ve never seen before, where the eyebrows elevate into an immobile superior frontalis.”

To avoid this when treating the forehead as well, he’s learned to split the dose of neuromodulator. “If I was injecting 5 units in the procerus before, I’ll do 2.5 units on nasal bone at the insertion of the muscle and then 2.5 units higher up in the traditional midline procerus injection site,” Dr. Green said.

“Same with the corrugators,” he continued. “Then, remember to inject more superficially in the lateral part, the tail of the corrugators, because the tail of the corrugators is inserting into the undersurface of the dermis. That’s why you see that skin puckering in the lateral brows when people frown. You’re pretty safe to chase that laterally if the brow’s already flat as in men, but I caution you [not] to do that in women, because you may flatten the brow.”

Dr. Green said that he is aware of two cases of lid ptosis from the 3-point technique, one of which happened to him.

“When you’re on the bone with your thumb you can feel that liquid traveling along the bone,” he said. “It can travel all the way to the midline pupil where the levator palpebrae superioris muscle is. I now don’t come in contact with bone with my corrugator origin injections, but rather float the needle a couple of millimeters off bone (in muscle) to hopefully prevent that from happening. Alternatively, some people will compress the brow along frontal bone lateral to that corrugator injection site while they’re injecting to prevent backflow of the neuromodulator.”

Dr. Green reported having received research funding and/or consulting fees from many device and pharmaceutical companies.

SAN DIEGO – In the clinical experience of Jeremy B. Green, MD, men typically require a higher dose of facial neuromodulators for nonsurgical wrinkle reduction compared with women because of anatomical differences.

“Men generally have larger facial muscle mass,” Dr. Green, a dermatologist in Coral Gables, Fla., said at the annual Masters of Aesthetics Symposium. “We need a higher dose to treat them, or they will not be happy. In general, I try to increase the dose by about 50% for my male patients.”

Two early trials of dose adjustments support this practice, he said. In one, 80 men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (Botox) in the glabellar area. The researchers found that the 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose.

In a subsequent study, researchers administered botulinum toxin type A (Dysport) 0.5 to 0.7 mL for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation at several time points up to 150 days post treatment. The median duration of effect was 109 days vs. 0 days for placebo in the blinded evaluator evaluation and 107 days vs. 0 for placebo in the patient self-evaluation.

Most injection algorithms for treating the glabella rely on a 5- or 7-point injection technique, but in 2021, researchers led by Sebastian Cotofana, MD, PhD, of the department of clinical anatomy at Mayo Clinic, Rochester, Minn., reported results from a study of the efficacy and safety of a refined 3-point injection technique targeting horizontal and vertical lines to prevent brow ptosis.

“Prior to this study Sebastian asked me, ‘Why do you guys always inject the body of the muscle?’ ” Dr. Green said. “‘If you inject the origin of the muscle on bone, you could more effectively wipe out the entire muscle’s movement. You’re going to get a better result at a lower dose, so let’s study this.’”

The injection technique involves targeting the midline level of the connecting line between left and right medial canthal ligaments with a 90-degree injection angle with bone contact, as well as the medial and inferior margin of eyebrows with a 45-degree injection angle in relation to midline with frontal bone contact. These three points are located inferior to the traditional (on-label) glabellar frown line injections used to treat the frontalis and the brow depressors.

The researchers used the 5-point glabellar line severity scale to evaluate the time of effect onset and the injection-related outcome 120 days after the treatment in 27 men and 78 women. They found that the onset of the neuromodulator effect occurred in an average of 3.5 days, and no adverse events such as eyebrow ptosis, upper eyelid ptosis, medial eyebrow ptosis, and lateral frontalis hyperactivity occurred during the study period.

“If you inject the origin of these muscles, you can get a brow lift with this technique by avoiding frontalis altogether,” Dr. Green said. “The caveat is, it’s so great at lifting the brows that if you treat the forehead, you may create a midline horizontal ‘shelf’ like I’ve never seen before, where the eyebrows elevate into an immobile superior frontalis.”

To avoid this when treating the forehead as well, he’s learned to split the dose of neuromodulator. “If I was injecting 5 units in the procerus before, I’ll do 2.5 units on nasal bone at the insertion of the muscle and then 2.5 units higher up in the traditional midline procerus injection site,” Dr. Green said.

“Same with the corrugators,” he continued. “Then, remember to inject more superficially in the lateral part, the tail of the corrugators, because the tail of the corrugators is inserting into the undersurface of the dermis. That’s why you see that skin puckering in the lateral brows when people frown. You’re pretty safe to chase that laterally if the brow’s already flat as in men, but I caution you [not] to do that in women, because you may flatten the brow.”

Dr. Green said that he is aware of two cases of lid ptosis from the 3-point technique, one of which happened to him.

“When you’re on the bone with your thumb you can feel that liquid traveling along the bone,” he said. “It can travel all the way to the midline pupil where the levator palpebrae superioris muscle is. I now don’t come in contact with bone with my corrugator origin injections, but rather float the needle a couple of millimeters off bone (in muscle) to hopefully prevent that from happening. Alternatively, some people will compress the brow along frontal bone lateral to that corrugator injection site while they’re injecting to prevent backflow of the neuromodulator.”

Dr. Green reported having received research funding and/or consulting fees from many device and pharmaceutical companies.

A gastroenterologist affiliated with the Cleveland Clinic was recently arrested and charged with multiple felonies.

According to Cleveland Municipal Court records, Omar Massoud, MD, PhD, of Westlake, Ohio, has been charged with three counts of kidnapping, all first-degree felonies, and three counts of gross sexual imposition, all third-degree felonies.

The assaults are alleged to have happened during liver examinations on March 25, Nov. 11, and Nov. 28, 2022 at Cleveland Clinic’s main campus located at 9500 Euclid Avenue.

No further details were provided.

Dr. Massoud is the former chief of hepatology at the Cleveland Clinic.

In a statement, the Cleveland Clinic said it “immediately reported the accusations to the appropriate law enforcement agencies and are fully cooperating with the investigations.”

“Following a thorough internal investigation,” Dr. Massoud was fired, the Cleveland Clinic said.

“Cleveland Clinic is strongly committed to protecting the rights and safety of our patients, visitors, and caregivers from any type of inappropriate behavior. We care deeply about patient safety and any form of misconduct is not tolerated,” the statement said.

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

A gastroenterologist affiliated with the Cleveland Clinic was recently arrested and charged with multiple felonies.

According to Cleveland Municipal Court records, Omar Massoud, MD, PhD, of Westlake, Ohio, has been charged with three counts of kidnapping, all first-degree felonies, and three counts of gross sexual imposition, all third-degree felonies.

The assaults are alleged to have happened during liver examinations on March 25, Nov. 11, and Nov. 28, 2022 at Cleveland Clinic’s main campus located at 9500 Euclid Avenue.

No further details were provided.

Dr. Massoud is the former chief of hepatology at the Cleveland Clinic.

In a statement, the Cleveland Clinic said it “immediately reported the accusations to the appropriate law enforcement agencies and are fully cooperating with the investigations.”

“Following a thorough internal investigation,” Dr. Massoud was fired, the Cleveland Clinic said.

“Cleveland Clinic is strongly committed to protecting the rights and safety of our patients, visitors, and caregivers from any type of inappropriate behavior. We care deeply about patient safety and any form of misconduct is not tolerated,” the statement said.

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

A gastroenterologist affiliated with the Cleveland Clinic was recently arrested and charged with multiple felonies.

According to Cleveland Municipal Court records, Omar Massoud, MD, PhD, of Westlake, Ohio, has been charged with three counts of kidnapping, all first-degree felonies, and three counts of gross sexual imposition, all third-degree felonies.

The assaults are alleged to have happened during liver examinations on March 25, Nov. 11, and Nov. 28, 2022 at Cleveland Clinic’s main campus located at 9500 Euclid Avenue.

No further details were provided.

Dr. Massoud is the former chief of hepatology at the Cleveland Clinic.

In a statement, the Cleveland Clinic said it “immediately reported the accusations to the appropriate law enforcement agencies and are fully cooperating with the investigations.”

“Following a thorough internal investigation,” Dr. Massoud was fired, the Cleveland Clinic said.

“Cleveland Clinic is strongly committed to protecting the rights and safety of our patients, visitors, and caregivers from any type of inappropriate behavior. We care deeply about patient safety and any form of misconduct is not tolerated,” the statement said.

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

Kiwifruit can increase the frequency of bowel movements for people with constipation, according to researchers in New Zealand.

“In addition to improved measures of constipation status, there was a significant improvement in stool consistency, reduction in constipation, indigestion/reflux, and abdominal pain resulting in an improved overall level of GI comfort,” write Richard Gearry, MD, PhD, of the University of Otago, New Zealand, and colleagues.

Dr. Gearry and colleagues describe their international multicenter controlled trial of kiwifruit as a constipation treatment in the American Journal of Gastroenterology.

Although constipation is common, previous researchers have reported a high rate of dissatisfaction with pharmaceutical treatments.

Fiber found in kiwifruit cell walls swells and holds water, which can soften stools and increase stool frequency. Other components of kiwifruit, such as raphides, may alter mucin production, leading to improved laxation.

Several previous studies have suggested that regular consumption of fresh, green kiwifruit may be effective as a treatment for constipation. However, these studies have typically been small with nonstandardized endpoints, Dr. Gearry and colleagues note. In their article, they did not comment on studies of other fresh fruits or vegetables as constipation treatments.

The researchers set out to test the benefits of the fruit in a more rigorous trial. They recruited adults in New Zealand, Italy, and Japan who had either functional constipation or constipation-predominant irritable bowel syndrome (IBS-C), as well as healthy people as controls. The primary difference between functional constipation and IBS-C is that people with IBS-C experience abdominal pain along with constipation, they write.

Between June 12, 2014, and June 17, 2017, 184 participants were enrolled. Participants included 136 women and 48 men, a proportion consistent with the gender prevalence of constipation. The mean age was 30.5 years in Japan, 36.9 years in Italy, and 44.8 years in New Zealand, and the mean body mass index was 20.6 in Japan, 23.0 in Italy, and 25.4 in New Zealand.

For 2 weeks following recruitment, the participants became accustomed to recording their bowel movements with respect to frequency, completeness, spontaneity, stool form, laxative use, and degree of straining.

Participants were then randomly assigned to consume either two ripe green kiwifruit (Actinidia chinensis var. deliciosa “Hayward”) without the skins, or 7.5 g of psyllium per day for 4 weeks. Psyllium is considered a first-line treatment for both the constipation conditions with which participants were diagnosed. The fiber content of psyllium is similar to that of kiwifruit.

After 4 weeks, treatments were stopped for 4 weeks as a washout period, after which patients were switched to the other treatment for another 4 weeks.

The researchers provided them with two bisacodyl (5-g suppositories) as a pharmacologic rescue therapy.

Overall, 169 participants completed the study, and compliance with diary completion was more than 80%.

At the end of the 4-week treatment periods, the people with functional constipation who ate kiwifruit demonstrated an average increase of 1.53 bowel movements per week, a statistically significant increase (P < .0001). Those with IBS-C demonstrated an increase of 1.73 (P = .0001). Both groups reported significantly improved gastrointestinal comfort on the gastrointestinal symptom rating scale.

The frequency of bowel movements in the healthy participants did not increase.

Among those participants who took psyllium, only those with IBS-C experienced a statistically significant increase in the frequency of their bowel movements or a decrease in their gastrointestinal symptoms. Their bowel movements increased by an average of 1.87 per week (P = .0051).

The participants who ate kiwifruit reported softening of stool consistency, reduction in straining, and improvement in quality of life compared with baseline, and these improvements in straining and stool consistency were better than was reported by those who took psyllium.

“Taken in conjunction with previous clinical trials of green kiwifruit and the emerging physiological data from functional studies, consumption of two green kiwifruit can be safely recommended as an effective treatment for constipation in those with functional gastrointestinal disorders that will also provide improvements in symptoms of GI comfort,” the researchers conclude.

Two of the researchers were employed by Zespri International, a cooperative of kiwifruit growers, which partially funded the study and approved its design. The New Zealand study center trial was jointly funded by a grant from the New Zealand government.

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

Kiwifruit can increase the frequency of bowel movements for people with constipation, according to researchers in New Zealand.

“In addition to improved measures of constipation status, there was a significant improvement in stool consistency, reduction in constipation, indigestion/reflux, and abdominal pain resulting in an improved overall level of GI comfort,” write Richard Gearry, MD, PhD, of the University of Otago, New Zealand, and colleagues.

Dr. Gearry and colleagues describe their international multicenter controlled trial of kiwifruit as a constipation treatment in the American Journal of Gastroenterology.

Although constipation is common, previous researchers have reported a high rate of dissatisfaction with pharmaceutical treatments.

Fiber found in kiwifruit cell walls swells and holds water, which can soften stools and increase stool frequency. Other components of kiwifruit, such as raphides, may alter mucin production, leading to improved laxation.

Several previous studies have suggested that regular consumption of fresh, green kiwifruit may be effective as a treatment for constipation. However, these studies have typically been small with nonstandardized endpoints, Dr. Gearry and colleagues note. In their article, they did not comment on studies of other fresh fruits or vegetables as constipation treatments.

The researchers set out to test the benefits of the fruit in a more rigorous trial. They recruited adults in New Zealand, Italy, and Japan who had either functional constipation or constipation-predominant irritable bowel syndrome (IBS-C), as well as healthy people as controls. The primary difference between functional constipation and IBS-C is that people with IBS-C experience abdominal pain along with constipation, they write.

Between June 12, 2014, and June 17, 2017, 184 participants were enrolled. Participants included 136 women and 48 men, a proportion consistent with the gender prevalence of constipation. The mean age was 30.5 years in Japan, 36.9 years in Italy, and 44.8 years in New Zealand, and the mean body mass index was 20.6 in Japan, 23.0 in Italy, and 25.4 in New Zealand.

For 2 weeks following recruitment, the participants became accustomed to recording their bowel movements with respect to frequency, completeness, spontaneity, stool form, laxative use, and degree of straining.

Participants were then randomly assigned to consume either two ripe green kiwifruit (Actinidia chinensis var. deliciosa “Hayward”) without the skins, or 7.5 g of psyllium per day for 4 weeks. Psyllium is considered a first-line treatment for both the constipation conditions with which participants were diagnosed. The fiber content of psyllium is similar to that of kiwifruit.

After 4 weeks, treatments were stopped for 4 weeks as a washout period, after which patients were switched to the other treatment for another 4 weeks.

The researchers provided them with two bisacodyl (5-g suppositories) as a pharmacologic rescue therapy.

Overall, 169 participants completed the study, and compliance with diary completion was more than 80%.

At the end of the 4-week treatment periods, the people with functional constipation who ate kiwifruit demonstrated an average increase of 1.53 bowel movements per week, a statistically significant increase (P < .0001). Those with IBS-C demonstrated an increase of 1.73 (P = .0001). Both groups reported significantly improved gastrointestinal comfort on the gastrointestinal symptom rating scale.

The frequency of bowel movements in the healthy participants did not increase.

Among those participants who took psyllium, only those with IBS-C experienced a statistically significant increase in the frequency of their bowel movements or a decrease in their gastrointestinal symptoms. Their bowel movements increased by an average of 1.87 per week (P = .0051).

The participants who ate kiwifruit reported softening of stool consistency, reduction in straining, and improvement in quality of life compared with baseline, and these improvements in straining and stool consistency were better than was reported by those who took psyllium.

“Taken in conjunction with previous clinical trials of green kiwifruit and the emerging physiological data from functional studies, consumption of two green kiwifruit can be safely recommended as an effective treatment for constipation in those with functional gastrointestinal disorders that will also provide improvements in symptoms of GI comfort,” the researchers conclude.

Two of the researchers were employed by Zespri International, a cooperative of kiwifruit growers, which partially funded the study and approved its design. The New Zealand study center trial was jointly funded by a grant from the New Zealand government.

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

Kiwifruit can increase the frequency of bowel movements for people with constipation, according to researchers in New Zealand.

“In addition to improved measures of constipation status, there was a significant improvement in stool consistency, reduction in constipation, indigestion/reflux, and abdominal pain resulting in an improved overall level of GI comfort,” write Richard Gearry, MD, PhD, of the University of Otago, New Zealand, and colleagues.

Dr. Gearry and colleagues describe their international multicenter controlled trial of kiwifruit as a constipation treatment in the American Journal of Gastroenterology.

Although constipation is common, previous researchers have reported a high rate of dissatisfaction with pharmaceutical treatments.

Fiber found in kiwifruit cell walls swells and holds water, which can soften stools and increase stool frequency. Other components of kiwifruit, such as raphides, may alter mucin production, leading to improved laxation.

Several previous studies have suggested that regular consumption of fresh, green kiwifruit may be effective as a treatment for constipation. However, these studies have typically been small with nonstandardized endpoints, Dr. Gearry and colleagues note. In their article, they did not comment on studies of other fresh fruits or vegetables as constipation treatments.

The researchers set out to test the benefits of the fruit in a more rigorous trial. They recruited adults in New Zealand, Italy, and Japan who had either functional constipation or constipation-predominant irritable bowel syndrome (IBS-C), as well as healthy people as controls. The primary difference between functional constipation and IBS-C is that people with IBS-C experience abdominal pain along with constipation, they write.

Between June 12, 2014, and June 17, 2017, 184 participants were enrolled. Participants included 136 women and 48 men, a proportion consistent with the gender prevalence of constipation. The mean age was 30.5 years in Japan, 36.9 years in Italy, and 44.8 years in New Zealand, and the mean body mass index was 20.6 in Japan, 23.0 in Italy, and 25.4 in New Zealand.

For 2 weeks following recruitment, the participants became accustomed to recording their bowel movements with respect to frequency, completeness, spontaneity, stool form, laxative use, and degree of straining.

Participants were then randomly assigned to consume either two ripe green kiwifruit (Actinidia chinensis var. deliciosa “Hayward”) without the skins, or 7.5 g of psyllium per day for 4 weeks. Psyllium is considered a first-line treatment for both the constipation conditions with which participants were diagnosed. The fiber content of psyllium is similar to that of kiwifruit.

After 4 weeks, treatments were stopped for 4 weeks as a washout period, after which patients were switched to the other treatment for another 4 weeks.

The researchers provided them with two bisacodyl (5-g suppositories) as a pharmacologic rescue therapy.

Overall, 169 participants completed the study, and compliance with diary completion was more than 80%.

At the end of the 4-week treatment periods, the people with functional constipation who ate kiwifruit demonstrated an average increase of 1.53 bowel movements per week, a statistically significant increase (P < .0001). Those with IBS-C demonstrated an increase of 1.73 (P = .0001). Both groups reported significantly improved gastrointestinal comfort on the gastrointestinal symptom rating scale.

The frequency of bowel movements in the healthy participants did not increase.

Among those participants who took psyllium, only those with IBS-C experienced a statistically significant increase in the frequency of their bowel movements or a decrease in their gastrointestinal symptoms. Their bowel movements increased by an average of 1.87 per week (P = .0051).

The participants who ate kiwifruit reported softening of stool consistency, reduction in straining, and improvement in quality of life compared with baseline, and these improvements in straining and stool consistency were better than was reported by those who took psyllium.

“Taken in conjunction with previous clinical trials of green kiwifruit and the emerging physiological data from functional studies, consumption of two green kiwifruit can be safely recommended as an effective treatment for constipation in those with functional gastrointestinal disorders that will also provide improvements in symptoms of GI comfort,” the researchers conclude.

Two of the researchers were employed by Zespri International, a cooperative of kiwifruit growers, which partially funded the study and approved its design. The New Zealand study center trial was jointly funded by a grant from the New Zealand government.

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

Among Hispanic/Latinx patients with alopecia areata, the mean age at diagnosis was 33 years, 24% had concomitant atopy, and 18% had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis.

Those are among key findings from a retrospective analysis of Hispanic/Latinx patients at the University of California, Irvine (UCI) by Natasha Mesinkovska, MD, PhD, of UCI’s department of dermatology, and her coauthors. The findings were published online in the Journal of the American Academy of Dermatology.

A recent study examined the epidemiology of alopecia areata (AA) in Black patients, wrote Dr. Mesinkovska and coauthors Celine Phong, a UCI medical student, and Amy J. McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C. “A similar unmet need exists to describe the characteristics of AA in Hispanic/Latinx (H/L) patients, the prevalent majority in California,” they added.

Drawing from chart reviews, ICD codes, and documented physical exams, they retrospectively identified 197 Hispanic/Latinx patients diagnosed with AA at UCI between 2015 and 2022, including alopecia totalis and alopecia universalis.

Nearly two-thirds of patients with alopecia were female (63%), and their mean age at diagnosis was 33 years. Most patients (79%) presented with patchy pattern AA, 13% had diffuse pattern AA, and only 12% had eyebrow, eyelash, or beard involvement. The most common comorbidity in patients overall was atopy (24%), including allergic rhinitis (12%), asthma (10%), and/or atopic dermatitis (7%).

The authors found that 18% of patients had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis (9%) and thyroid disease (6%). No patients had celiac disease, myasthenia gravis, or inflammatory bowel disease, but 43% had another dermatologic condition.

In other findings, 22% of patients had vitamin D deficiency, 20% had hyperlipidemia, 18% had obesity, 16% had gastroesophageal reflux disease, and 12% had anemia. At the same time, depression, anxiety, or sleep disorders were identified in 14% of patients.

“Interestingly, the most common autoimmune comorbidity in H/L was rheumatoid arthritis, compared to thyroid disease in Black patients and overall AA patients,” the authors wrote. “This finding may be a reflection of a larger trend, as rheumatoid arthritis in the H/L population has been on the rise.”

The authors acknowledged certain limitations of the study including its small sample size and lack of a control group, and reported having no financial disclosures.

Among Hispanic/Latinx patients with alopecia areata, the mean age at diagnosis was 33 years, 24% had concomitant atopy, and 18% had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis.

Those are among key findings from a retrospective analysis of Hispanic/Latinx patients at the University of California, Irvine (UCI) by Natasha Mesinkovska, MD, PhD, of UCI’s department of dermatology, and her coauthors. The findings were published online in the Journal of the American Academy of Dermatology.

A recent study examined the epidemiology of alopecia areata (AA) in Black patients, wrote Dr. Mesinkovska and coauthors Celine Phong, a UCI medical student, and Amy J. McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C. “A similar unmet need exists to describe the characteristics of AA in Hispanic/Latinx (H/L) patients, the prevalent majority in California,” they added.

Drawing from chart reviews, ICD codes, and documented physical exams, they retrospectively identified 197 Hispanic/Latinx patients diagnosed with AA at UCI between 2015 and 2022, including alopecia totalis and alopecia universalis.

Nearly two-thirds of patients with alopecia were female (63%), and their mean age at diagnosis was 33 years. Most patients (79%) presented with patchy pattern AA, 13% had diffuse pattern AA, and only 12% had eyebrow, eyelash, or beard involvement. The most common comorbidity in patients overall was atopy (24%), including allergic rhinitis (12%), asthma (10%), and/or atopic dermatitis (7%).

The authors found that 18% of patients had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis (9%) and thyroid disease (6%). No patients had celiac disease, myasthenia gravis, or inflammatory bowel disease, but 43% had another dermatologic condition.

In other findings, 22% of patients had vitamin D deficiency, 20% had hyperlipidemia, 18% had obesity, 16% had gastroesophageal reflux disease, and 12% had anemia. At the same time, depression, anxiety, or sleep disorders were identified in 14% of patients.

“Interestingly, the most common autoimmune comorbidity in H/L was rheumatoid arthritis, compared to thyroid disease in Black patients and overall AA patients,” the authors wrote. “This finding may be a reflection of a larger trend, as rheumatoid arthritis in the H/L population has been on the rise.”

The authors acknowledged certain limitations of the study including its small sample size and lack of a control group, and reported having no financial disclosures.

Among Hispanic/Latinx patients with alopecia areata, the mean age at diagnosis was 33 years, 24% had concomitant atopy, and 18% had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis.

Those are among key findings from a retrospective analysis of Hispanic/Latinx patients at the University of California, Irvine (UCI) by Natasha Mesinkovska, MD, PhD, of UCI’s department of dermatology, and her coauthors. The findings were published online in the Journal of the American Academy of Dermatology.

A recent study examined the epidemiology of alopecia areata (AA) in Black patients, wrote Dr. Mesinkovska and coauthors Celine Phong, a UCI medical student, and Amy J. McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C. “A similar unmet need exists to describe the characteristics of AA in Hispanic/Latinx (H/L) patients, the prevalent majority in California,” they added.

Drawing from chart reviews, ICD codes, and documented physical exams, they retrospectively identified 197 Hispanic/Latinx patients diagnosed with AA at UCI between 2015 and 2022, including alopecia totalis and alopecia universalis.

Nearly two-thirds of patients with alopecia were female (63%), and their mean age at diagnosis was 33 years. Most patients (79%) presented with patchy pattern AA, 13% had diffuse pattern AA, and only 12% had eyebrow, eyelash, or beard involvement. The most common comorbidity in patients overall was atopy (24%), including allergic rhinitis (12%), asthma (10%), and/or atopic dermatitis (7%).

The authors found that 18% of patients had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis (9%) and thyroid disease (6%). No patients had celiac disease, myasthenia gravis, or inflammatory bowel disease, but 43% had another dermatologic condition.

In other findings, 22% of patients had vitamin D deficiency, 20% had hyperlipidemia, 18% had obesity, 16% had gastroesophageal reflux disease, and 12% had anemia. At the same time, depression, anxiety, or sleep disorders were identified in 14% of patients.

“Interestingly, the most common autoimmune comorbidity in H/L was rheumatoid arthritis, compared to thyroid disease in Black patients and overall AA patients,” the authors wrote. “This finding may be a reflection of a larger trend, as rheumatoid arthritis in the H/L population has been on the rise.”

The authors acknowledged certain limitations of the study including its small sample size and lack of a control group, and reported having no financial disclosures.