MDedge Dermatology

Practice Gap

Perioperative anxiety is common in patients undergoing nail surgery. Patients might worry about seeing blood; about the procedure itself, including nail avulsion; and about associated pain and disfigurement. Nail surgery causes a high level of anxiety that correlates positively with postoperative pain¹ and overall patient dissatisfaction. Furthermore, surgery-related anxiety is a predictor of increased postoperative analgesic use² and delayed recovery.³

Therefore, implementing strategies that reduce perioperative anxiety may help minimize postoperative pain. Squeezing a stress ball, hand-holding, virtual reality, and music are tools that have been studied to reduce anxiety in the context of Mohs micrographic surgery; these strategies have not been studied for nail surgery.

The Technique

Using a sleep mask is a practical solution to reduce patient anxiety during nail surgery. A minority of patients will choose to watch their surgical procedure; most become unnerved observing their nail surgery. Using a sleep mask diverts visual attention from the surgical field without physically interfering with the nail surgeon. Utilizing a sleep mask is cost-effective, with disposable sleep masks available online for less than $0.30 each. Patients can bring their own mask, or a mask can be offered prior to surgery.

If desired, patients are instructed to wear the sleep mask during the entirety of the procedure, starting from anesthetic infiltration until wound closure and dressing application. Any adjustments can be made with the patient’s free hand. The sleep mask can be offered to patients of all ages undergoing nail surgery under local anesthesia, except babies and young children, who require general anesthesia.

Practical Implications

Distraction is an important strategy to reduce anxiety and pain in patients undergoing surgical procedures. In an observational study of 3087 surgical patients, 36% reported that self-distraction was the most helpful strategy for coping with preoperative anxiety.⁴ In a randomized, open-label clinical trial of 72 patients undergoing peripheral venous catheterization, asking the patients simple questions during the procedure was more effective than local anesthesia in reducing the perception of pain.⁵

It is crucial to implement strategies to reduce anxiety in patients undergoing nail surgery. Using a sleep mask impedes direct visualization of the surgical field, thus distracting the patient’s sight and attention from the procedure. Furthermore, this technique is safe and cost-effective.

Controlled clinical trials are necessary to assess the efficacy of this method in reducing nail surgery–related anxiety in comparison to other techniques.

Practice Gap

Perioperative anxiety is common in patients undergoing nail surgery. Patients might worry about seeing blood; about the procedure itself, including nail avulsion; and about associated pain and disfigurement. Nail surgery causes a high level of anxiety that correlates positively with postoperative pain¹ and overall patient dissatisfaction. Furthermore, surgery-related anxiety is a predictor of increased postoperative analgesic use² and delayed recovery.³

Therefore, implementing strategies that reduce perioperative anxiety may help minimize postoperative pain. Squeezing a stress ball, hand-holding, virtual reality, and music are tools that have been studied to reduce anxiety in the context of Mohs micrographic surgery; these strategies have not been studied for nail surgery.

The Technique

Using a sleep mask is a practical solution to reduce patient anxiety during nail surgery. A minority of patients will choose to watch their surgical procedure; most become unnerved observing their nail surgery. Using a sleep mask diverts visual attention from the surgical field without physically interfering with the nail surgeon. Utilizing a sleep mask is cost-effective, with disposable sleep masks available online for less than $0.30 each. Patients can bring their own mask, or a mask can be offered prior to surgery.

If desired, patients are instructed to wear the sleep mask during the entirety of the procedure, starting from anesthetic infiltration until wound closure and dressing application. Any adjustments can be made with the patient’s free hand. The sleep mask can be offered to patients of all ages undergoing nail surgery under local anesthesia, except babies and young children, who require general anesthesia.

Practical Implications

Distraction is an important strategy to reduce anxiety and pain in patients undergoing surgical procedures. In an observational study of 3087 surgical patients, 36% reported that self-distraction was the most helpful strategy for coping with preoperative anxiety.⁴ In a randomized, open-label clinical trial of 72 patients undergoing peripheral venous catheterization, asking the patients simple questions during the procedure was more effective than local anesthesia in reducing the perception of pain.⁵

It is crucial to implement strategies to reduce anxiety in patients undergoing nail surgery. Using a sleep mask impedes direct visualization of the surgical field, thus distracting the patient’s sight and attention from the procedure. Furthermore, this technique is safe and cost-effective.

Controlled clinical trials are necessary to assess the efficacy of this method in reducing nail surgery–related anxiety in comparison to other techniques.

Practice Gap

Perioperative anxiety is common in patients undergoing nail surgery. Patients might worry about seeing blood; about the procedure itself, including nail avulsion; and about associated pain and disfigurement. Nail surgery causes a high level of anxiety that correlates positively with postoperative pain¹ and overall patient dissatisfaction. Furthermore, surgery-related anxiety is a predictor of increased postoperative analgesic use² and delayed recovery.³

Therefore, implementing strategies that reduce perioperative anxiety may help minimize postoperative pain. Squeezing a stress ball, hand-holding, virtual reality, and music are tools that have been studied to reduce anxiety in the context of Mohs micrographic surgery; these strategies have not been studied for nail surgery.

The Technique

Using a sleep mask is a practical solution to reduce patient anxiety during nail surgery. A minority of patients will choose to watch their surgical procedure; most become unnerved observing their nail surgery. Using a sleep mask diverts visual attention from the surgical field without physically interfering with the nail surgeon. Utilizing a sleep mask is cost-effective, with disposable sleep masks available online for less than $0.30 each. Patients can bring their own mask, or a mask can be offered prior to surgery.

If desired, patients are instructed to wear the sleep mask during the entirety of the procedure, starting from anesthetic infiltration until wound closure and dressing application. Any adjustments can be made with the patient’s free hand. The sleep mask can be offered to patients of all ages undergoing nail surgery under local anesthesia, except babies and young children, who require general anesthesia.

Practical Implications

Distraction is an important strategy to reduce anxiety and pain in patients undergoing surgical procedures. In an observational study of 3087 surgical patients, 36% reported that self-distraction was the most helpful strategy for coping with preoperative anxiety.⁴ In a randomized, open-label clinical trial of 72 patients undergoing peripheral venous catheterization, asking the patients simple questions during the procedure was more effective than local anesthesia in reducing the perception of pain.⁵

It is crucial to implement strategies to reduce anxiety in patients undergoing nail surgery. Using a sleep mask impedes direct visualization of the surgical field, thus distracting the patient’s sight and attention from the procedure. Furthermore, this technique is safe and cost-effective.

Controlled clinical trials are necessary to assess the efficacy of this method in reducing nail surgery–related anxiety in comparison to other techniques.

Congenital onychodysplasia of the index finger (COIF), or Iso-Kikuchi syndrome, is a rare disorder characterized by malformation of one or both nails of the index fingers. The various anomalies described are anonychia, micronychia, polyonychia, malalignment, or hemi-onychogryphosis. It may be associated with abnormalities of the underlying phalangeal bone, the most masked being bifurcation of the terminal phalange.¹ Initially thought to be nonhereditary and nonfamilial,² it is now known that COIF can be inherited in an autosomal-dominant fashion.³ Millman and Strier³ described a family of 9 patients with COIF. It rarely is described outside of Japan. Padmavathy et al⁴ described a case in an Indian patient with COIF that was associated with the absence of a ring finger in addition to anomalies of the metacarpal bones.

Congenital onychodysplasia of the index finger has a broad spectrum regarding its etiology and clinical features.⁵ The pathogenesis of COIF still is poorly understood. Deficient circulation in digital arteries is thought to be a putative mechanism for developing a deformed nail. The nail is affected on the radial side of the index finger, likely because of the smaller caliber of the artery on that side.⁵ Hereditary as well as nonhereditary sporadic cases have been reported. In addition to the various fingernail anomalies, skeletal abnormalities also have been reported. Baran and Stroud⁶ have reported deformed lunulae as a manifestation of COIF.

The Diagnosis: Congenital Onychodysplasia of the Index Finger

The differential diagnosis of COIF includes hidrotic ectodermal dysplasia, nail-patella syndrome, Poland syndrome, and DOOR syndrome. Hidrotic ectodermal dysplasia exhibits onychodystrophy, generalized hypotrichosis, palmoplantar keratoderma, and dental anomalies.⁷ Nail-patella syndrome presents with hypoplasia of the fingernails and toenails, triangular nail lunulae, absent or hypoplastic patellae, and elbow and iliac horn dysplasia. Poland syndrome is distinguished from COIF by the congenital absence of the pectoralis major muscle on the ipsilateral side of the involved digits. The DOOR syndrome tetrad is comprised of deafness, onychodystrophy, osteodystrophy, and mental retardation.⁸ Unlike these conditions, COIF does not involve systems other than the nails and phalanges.

Treatment of this condition is mainly conservative, as patients typically do not have symptoms.⁹ Surgical interventions can be considered for cosmetic concerns. Knowledge of this congenital entity and its clinical findings is essential to prevent unnecessary procedures and workup.

Congenital onychodysplasia of the index finger (COIF), or Iso-Kikuchi syndrome, is a rare disorder characterized by malformation of one or both nails of the index fingers. The various anomalies described are anonychia, micronychia, polyonychia, malalignment, or hemi-onychogryphosis. It may be associated with abnormalities of the underlying phalangeal bone, the most masked being bifurcation of the terminal phalange.¹ Initially thought to be nonhereditary and nonfamilial,² it is now known that COIF can be inherited in an autosomal-dominant fashion.³ Millman and Strier³ described a family of 9 patients with COIF. It rarely is described outside of Japan. Padmavathy et al⁴ described a case in an Indian patient with COIF that was associated with the absence of a ring finger in addition to anomalies of the metacarpal bones.

Congenital onychodysplasia of the index finger has a broad spectrum regarding its etiology and clinical features.⁵ The pathogenesis of COIF still is poorly understood. Deficient circulation in digital arteries is thought to be a putative mechanism for developing a deformed nail. The nail is affected on the radial side of the index finger, likely because of the smaller caliber of the artery on that side.⁵ Hereditary as well as nonhereditary sporadic cases have been reported. In addition to the various fingernail anomalies, skeletal abnormalities also have been reported. Baran and Stroud⁶ have reported deformed lunulae as a manifestation of COIF.

The Diagnosis: Congenital Onychodysplasia of the Index Finger

The differential diagnosis of COIF includes hidrotic ectodermal dysplasia, nail-patella syndrome, Poland syndrome, and DOOR syndrome. Hidrotic ectodermal dysplasia exhibits onychodystrophy, generalized hypotrichosis, palmoplantar keratoderma, and dental anomalies.⁷ Nail-patella syndrome presents with hypoplasia of the fingernails and toenails, triangular nail lunulae, absent or hypoplastic patellae, and elbow and iliac horn dysplasia. Poland syndrome is distinguished from COIF by the congenital absence of the pectoralis major muscle on the ipsilateral side of the involved digits. The DOOR syndrome tetrad is comprised of deafness, onychodystrophy, osteodystrophy, and mental retardation.⁸ Unlike these conditions, COIF does not involve systems other than the nails and phalanges.

Treatment of this condition is mainly conservative, as patients typically do not have symptoms.⁹ Surgical interventions can be considered for cosmetic concerns. Knowledge of this congenital entity and its clinical findings is essential to prevent unnecessary procedures and workup.

Congenital onychodysplasia of the index finger (COIF), or Iso-Kikuchi syndrome, is a rare disorder characterized by malformation of one or both nails of the index fingers. The various anomalies described are anonychia, micronychia, polyonychia, malalignment, or hemi-onychogryphosis. It may be associated with abnormalities of the underlying phalangeal bone, the most masked being bifurcation of the terminal phalange.¹ Initially thought to be nonhereditary and nonfamilial,² it is now known that COIF can be inherited in an autosomal-dominant fashion.³ Millman and Strier³ described a family of 9 patients with COIF. It rarely is described outside of Japan. Padmavathy et al⁴ described a case in an Indian patient with COIF that was associated with the absence of a ring finger in addition to anomalies of the metacarpal bones.

Congenital onychodysplasia of the index finger has a broad spectrum regarding its etiology and clinical features.⁵ The pathogenesis of COIF still is poorly understood. Deficient circulation in digital arteries is thought to be a putative mechanism for developing a deformed nail. The nail is affected on the radial side of the index finger, likely because of the smaller caliber of the artery on that side.⁵ Hereditary as well as nonhereditary sporadic cases have been reported. In addition to the various fingernail anomalies, skeletal abnormalities also have been reported. Baran and Stroud⁶ have reported deformed lunulae as a manifestation of COIF.

The Diagnosis: Congenital Onychodysplasia of the Index Finger

The differential diagnosis of COIF includes hidrotic ectodermal dysplasia, nail-patella syndrome, Poland syndrome, and DOOR syndrome. Hidrotic ectodermal dysplasia exhibits onychodystrophy, generalized hypotrichosis, palmoplantar keratoderma, and dental anomalies.⁷ Nail-patella syndrome presents with hypoplasia of the fingernails and toenails, triangular nail lunulae, absent or hypoplastic patellae, and elbow and iliac horn dysplasia. Poland syndrome is distinguished from COIF by the congenital absence of the pectoralis major muscle on the ipsilateral side of the involved digits. The DOOR syndrome tetrad is comprised of deafness, onychodystrophy, osteodystrophy, and mental retardation.⁸ Unlike these conditions, COIF does not involve systems other than the nails and phalanges.

Treatment of this condition is mainly conservative, as patients typically do not have symptoms.⁹ Surgical interventions can be considered for cosmetic concerns. Knowledge of this congenital entity and its clinical findings is essential to prevent unnecessary procedures and workup.

Medicare intends next year to allow physician assistants (PAs) to begin directly billing for their work and to expand coverage of telehealth services. It also intends to change the approach to payments for office visits and for coaching programs for diabetes prevention.

adventtr/iStock/Getty Images Plus

The Centers for Medicare & Medicaid Services recently posted its proposed 2022 physician fee schedule. Running to more than 1,700 pages, the draft rule contains myriad other changes in how the giant federal health program pays for medical care, including revisions to its approach to evaluation and management (E/M) services, which represent many office visits. In addition, Medicare is seeking to increase participation in a program intended to prevent people from developing diabetes.

Physician groups posted quick complaints about a proposed 3.75% reduction to the conversion factor because of budget neutrality requirements. The cut reinstates a reduction Congress prevented in late 2020.

In a statement, Anders Gilberg, senior vice president of government affairs for the Medical Group Management Association, called the draft rule a “mixed bag for physician practices.” Mr. Gilberg said the MGMA will seek congressional intervention to avert the cut for services in 2022.

In keeping with a provision Congress included in a massive spending bill enacted in December, Medicare will let PAs directly bill, as nurse practitioners already can. In a press release, CMS on July 13 described this as a move likely to expand access to care and reduce administrative burden. In 2020, the American Academy of PAs praised the inclusion in the spending bill of the provision allowing its members to directly bill Medicare.

In the draft rule, CMS also intends to remove certain geographic restrictions regarding use of telehealth services for diagnosis, evaluation, and treatment of mental health disorders. CMS also is proposing to allow payment to eligible clinicians for certain mental health and behavioral health services to patients via audio-only telephone calls. These services would include counseling and therapy services provided through opioid treatment programs.

“These changes would be particularly helpful for those in areas with poor broadband infrastructure and among people with Medicare who are not capable of, or do not consent to the use of, devices that permit a two-way, audio/video interaction for their health care visits,” CMS said in a statement.
 

Slimmer Medicare enrollees, bigger payments for coaches?

CMS is seeking to draw more participants to the Medicare Diabetes Prevention Program (MDPP). This program includes organizations that provide structured, coach-led sessions in community and health care settings to help people lose weight and exercise more. During the COVID-19 public health emergency, CMS waived an enrollment fee for new suppliers of services in MDPP. CMS now is proposing to waive this fee for all organizations that submit an application to enroll in Medicare as an MDPP supplier on or after Jan. 1, 2022.

Another proposed change in MDPP services is a restructuring of payments so that organizations involved in coaching would receive larger payments when their participants reach milestones for attendance and for becoming slimmer.

“We propose to increase performance payments for MDPP beneficiary achievement of the 5% weight-loss goal, as well as continued attendance during each core maintenance interval,” CMS said in a statement.

Medicare remains engaged in a review of its payments for E/M services. In the draft rule, CMS is proposing a number of refinements to current policies for split, or shared, E/M visits, critical care services, and services furnished by teaching physicians involving residents. The intention of these changes is to “better reflect the current practice of medicine, the evolving role of nonphysician practitioners as members of the medical team, and to clarify conditions of payment that must be met to bill Medicare for these services,” CMS said.

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

Medicare intends next year to allow physician assistants (PAs) to begin directly billing for their work and to expand coverage of telehealth services. It also intends to change the approach to payments for office visits and for coaching programs for diabetes prevention.

adventtr/iStock/Getty Images Plus

The Centers for Medicare & Medicaid Services recently posted its proposed 2022 physician fee schedule. Running to more than 1,700 pages, the draft rule contains myriad other changes in how the giant federal health program pays for medical care, including revisions to its approach to evaluation and management (E/M) services, which represent many office visits. In addition, Medicare is seeking to increase participation in a program intended to prevent people from developing diabetes.

Physician groups posted quick complaints about a proposed 3.75% reduction to the conversion factor because of budget neutrality requirements. The cut reinstates a reduction Congress prevented in late 2020.

In a statement, Anders Gilberg, senior vice president of government affairs for the Medical Group Management Association, called the draft rule a “mixed bag for physician practices.” Mr. Gilberg said the MGMA will seek congressional intervention to avert the cut for services in 2022.

In keeping with a provision Congress included in a massive spending bill enacted in December, Medicare will let PAs directly bill, as nurse practitioners already can. In a press release, CMS on July 13 described this as a move likely to expand access to care and reduce administrative burden. In 2020, the American Academy of PAs praised the inclusion in the spending bill of the provision allowing its members to directly bill Medicare.

In the draft rule, CMS also intends to remove certain geographic restrictions regarding use of telehealth services for diagnosis, evaluation, and treatment of mental health disorders. CMS also is proposing to allow payment to eligible clinicians for certain mental health and behavioral health services to patients via audio-only telephone calls. These services would include counseling and therapy services provided through opioid treatment programs.

“These changes would be particularly helpful for those in areas with poor broadband infrastructure and among people with Medicare who are not capable of, or do not consent to the use of, devices that permit a two-way, audio/video interaction for their health care visits,” CMS said in a statement.
 

Slimmer Medicare enrollees, bigger payments for coaches?

CMS is seeking to draw more participants to the Medicare Diabetes Prevention Program (MDPP). This program includes organizations that provide structured, coach-led sessions in community and health care settings to help people lose weight and exercise more. During the COVID-19 public health emergency, CMS waived an enrollment fee for new suppliers of services in MDPP. CMS now is proposing to waive this fee for all organizations that submit an application to enroll in Medicare as an MDPP supplier on or after Jan. 1, 2022.

Another proposed change in MDPP services is a restructuring of payments so that organizations involved in coaching would receive larger payments when their participants reach milestones for attendance and for becoming slimmer.

“We propose to increase performance payments for MDPP beneficiary achievement of the 5% weight-loss goal, as well as continued attendance during each core maintenance interval,” CMS said in a statement.

Medicare remains engaged in a review of its payments for E/M services. In the draft rule, CMS is proposing a number of refinements to current policies for split, or shared, E/M visits, critical care services, and services furnished by teaching physicians involving residents. The intention of these changes is to “better reflect the current practice of medicine, the evolving role of nonphysician practitioners as members of the medical team, and to clarify conditions of payment that must be met to bill Medicare for these services,” CMS said.

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

Medicare intends next year to allow physician assistants (PAs) to begin directly billing for their work and to expand coverage of telehealth services. It also intends to change the approach to payments for office visits and for coaching programs for diabetes prevention.

adventtr/iStock/Getty Images Plus

The Centers for Medicare & Medicaid Services recently posted its proposed 2022 physician fee schedule. Running to more than 1,700 pages, the draft rule contains myriad other changes in how the giant federal health program pays for medical care, including revisions to its approach to evaluation and management (E/M) services, which represent many office visits. In addition, Medicare is seeking to increase participation in a program intended to prevent people from developing diabetes.

Physician groups posted quick complaints about a proposed 3.75% reduction to the conversion factor because of budget neutrality requirements. The cut reinstates a reduction Congress prevented in late 2020.

In a statement, Anders Gilberg, senior vice president of government affairs for the Medical Group Management Association, called the draft rule a “mixed bag for physician practices.” Mr. Gilberg said the MGMA will seek congressional intervention to avert the cut for services in 2022.

In keeping with a provision Congress included in a massive spending bill enacted in December, Medicare will let PAs directly bill, as nurse practitioners already can. In a press release, CMS on July 13 described this as a move likely to expand access to care and reduce administrative burden. In 2020, the American Academy of PAs praised the inclusion in the spending bill of the provision allowing its members to directly bill Medicare.

In the draft rule, CMS also intends to remove certain geographic restrictions regarding use of telehealth services for diagnosis, evaluation, and treatment of mental health disorders. CMS also is proposing to allow payment to eligible clinicians for certain mental health and behavioral health services to patients via audio-only telephone calls. These services would include counseling and therapy services provided through opioid treatment programs.

“These changes would be particularly helpful for those in areas with poor broadband infrastructure and among people with Medicare who are not capable of, or do not consent to the use of, devices that permit a two-way, audio/video interaction for their health care visits,” CMS said in a statement.
 

Slimmer Medicare enrollees, bigger payments for coaches?

CMS is seeking to draw more participants to the Medicare Diabetes Prevention Program (MDPP). This program includes organizations that provide structured, coach-led sessions in community and health care settings to help people lose weight and exercise more. During the COVID-19 public health emergency, CMS waived an enrollment fee for new suppliers of services in MDPP. CMS now is proposing to waive this fee for all organizations that submit an application to enroll in Medicare as an MDPP supplier on or after Jan. 1, 2022.

Another proposed change in MDPP services is a restructuring of payments so that organizations involved in coaching would receive larger payments when their participants reach milestones for attendance and for becoming slimmer.

“We propose to increase performance payments for MDPP beneficiary achievement of the 5% weight-loss goal, as well as continued attendance during each core maintenance interval,” CMS said in a statement.

Medicare remains engaged in a review of its payments for E/M services. In the draft rule, CMS is proposing a number of refinements to current policies for split, or shared, E/M visits, critical care services, and services furnished by teaching physicians involving residents. The intention of these changes is to “better reflect the current practice of medicine, the evolving role of nonphysician practitioners as members of the medical team, and to clarify conditions of payment that must be met to bill Medicare for these services,” CMS said.

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

The heterogeneous clinical course of atopic dermatitis (AD) and its differing signs, symptoms, burden, and response to treatment can pose a quandary for physicians.

This is behind a new classification framework called DESCRIBE-AD, proposed by Jonathan I. Silverberg, MD, PhD, MPH, not only as a way to standardize the assessment of AD in clinical practice – but also to improve the classification of AD in clinical practice and clinical trials, facilitate tailoring of therapy to individual patient characteristics, and better identify therapeutically relevant disease subsets.

Dr. Silverberg, director of clinical research in the department of dermatology at George Washington University, Washington, debuted DESCRIBE-AD during the Revolutionizing Atopic Dermatitis symposium. The “D” in the mnemonic stands for dermatitis morphology and phenotype, the “E” for evolution of disease, the “S” for symptom severity, the “C” for comorbid health disorders, the “R” for response to therapy, the “I” for intensity of lesions, the “B” for burden of disease, and the “E” for extent of lesions.

At the meeting, he discussed the concepts behind each letter of the mnemonic.
 

Dermatitis morphology and phenotype

In the dermatitis morphology and phenotype component of DESCRIBE-AD, “there’s a lot to consider,” he said. “There are chronic signs like lichenification and prurigo nodules, which have treatment ramifications,” such as the length of time patients may need to be treated, and possibly “the use of more potent, targeted options to go after some of these lesions.”

Recent studies suggest that nummular lesions have a different underlying pathogenesis suggesting an overlap between Th2 and Th17 cell–mediated lesions. “How does that impact response to targeted therapies?” he asked. “We have no idea. We need to learn that.” He noted that psoriasiform lesions are not limited to Asian patients, but also appear in elderly patients with AD. “They look different [in elderly patients] and they may respond differently; they have more psoriasiform lesions and it’s not exactly clear why.”

Other morphologic variants of AD to be aware of include follicular eczema, xerosis, and the itch-dominant form, which Dr. Silverberg and colleagues addressed in a recently published study. “There are some patients who have milder-looking lesions, but their itch is just out of control,” he said. “This is a pattern that we need to recognize.”

Evolution of disease, symptom severity

Factors to consider for the evolution of disease component of the proposed classification include age of AD onset or disease recurrence, frequency and duration of flares, disease activity between flares, periods of disease clearance, and the overall disease trajectory. “We do get patients who say that every year their disease seems to get worse over time, for reasons that are not always clear,” Dr. Silverberg said.

Assessment tools he recommends for the symptom severity component of DESCRIBE-AD include the patient-reported global AD severity, numerical rating scale (NRS) worst or average itch in the past 7 days, the Skin Pain NRS, and the Sleep Quality NRS, which each take fewer than 30 seconds to complete. “You can have your nurses do this or can you have the patients fill out the form in the waiting area before they see you,” Dr. Silverberg said.

He also advises asking patients about the number of nights they experience sleep disturbance and if they have difficulty falling asleep or have nighttime awakenings because of their AD. Symptoms of anxiety and depression can be assessed with the Hospital Anxiety and Depression Scale and the Patient-Health Questionnaire–9, which each take 2-3 minutes to complete.

Recommended assessment tools for other symptoms – such as bleeding, oozing, and xerosis – include the Patient-Oriented Eczema Measure, which takes 2-3 minutes to complete, and the Atopic Dermatitis Control Tool or the Recap of Atopic Eczema, which each take 2-3 minutes to complete.
 

Comorbid health disorders

Comorbid health disorders linked to AD are varied and include atopic comorbidities such as asthma or wheeze, hay fever or oculonasal symptoms, food allergy, recurrent infections such as herpes simplex virus, mental health disorders, alopecia areata, Th1-mediated comorbidities, and adverse events to medication such as venous thromboembolism, hypertension, and impaired renal or liver function. “All of these are important because if the patients have these at baseline, they may not be good candidates for some therapies that cause these types of side effects,” Dr. Silverberg said.

Response to therapy, intensity of lesions

As for response to therapy, clinicians can ask patients, “How do you feel you’re improving?” But it’s also important to assess the signs, symptoms, frequency of flares, and comorbidities as part of that response to therapy, “and of course the adverse events and treatment burden,” he said.

For the intensity of lesions component of DESCRIBE-AD, Dr. Silverberg said that the Investigator’s Global Assessment–AD is an effective tool for clinical use. “You can also use tools like the Eczema Area and Severity Index or the Scoring AD, but recognize these are challenging,” and can be difficult to use if not well trained to use them, he said. “At the very least, do an Investigator’s Global Assessment and do a body surface area measurement.”

In his opinion, four key signs that should be assessed in clinical trials are erythema, edema/papulation, excoriation, and lichenification/prurigo nodules.
 

Burden of disease

In terms of assessing AD disease burden, guidelines from the American Academy of Dermatology don’t give a specific tool to use, but recommend asking open-ended questions, Dr. Silverberg said. “I would not recommend that, because when you ask an open-ended question, the flood gates open up because most patients are suffering miserably with this disease when it’s uncontrolled.

“That’s why it’s valuable to use structured, validated tools like the Dermatology Life Quality Index and the Patient Reported Outcome Measurement Information System. They don’t take a lot of time to complete, and you can look at the score and determine how burdensome their disease is, even in a busy clinical practice. They’re not going to slow you down; they’re going to speed you up and make you better at your therapeutic decision-making. I can guarantee you that most patients will love you for it. Sometimes patients say to me, ‘you’re the first doctor to ask these questions.’ ”
 

Extent of disease

Finally, for the extent of disease component of DESCRIBE-AD, he emphasized the importance of doing a full-body exam to appreciate the affected body surface area, flexural versus extensor distribution, and involvement and severity of disease on special sites such as the face, hands, feet, genitals, and scalp.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

[email protected]

The heterogeneous clinical course of atopic dermatitis (AD) and its differing signs, symptoms, burden, and response to treatment can pose a quandary for physicians.

This is behind a new classification framework called DESCRIBE-AD, proposed by Jonathan I. Silverberg, MD, PhD, MPH, not only as a way to standardize the assessment of AD in clinical practice – but also to improve the classification of AD in clinical practice and clinical trials, facilitate tailoring of therapy to individual patient characteristics, and better identify therapeutically relevant disease subsets.

Dr. Silverberg, director of clinical research in the department of dermatology at George Washington University, Washington, debuted DESCRIBE-AD during the Revolutionizing Atopic Dermatitis symposium. The “D” in the mnemonic stands for dermatitis morphology and phenotype, the “E” for evolution of disease, the “S” for symptom severity, the “C” for comorbid health disorders, the “R” for response to therapy, the “I” for intensity of lesions, the “B” for burden of disease, and the “E” for extent of lesions.

At the meeting, he discussed the concepts behind each letter of the mnemonic.
 

Dermatitis morphology and phenotype

In the dermatitis morphology and phenotype component of DESCRIBE-AD, “there’s a lot to consider,” he said. “There are chronic signs like lichenification and prurigo nodules, which have treatment ramifications,” such as the length of time patients may need to be treated, and possibly “the use of more potent, targeted options to go after some of these lesions.”

Recent studies suggest that nummular lesions have a different underlying pathogenesis suggesting an overlap between Th2 and Th17 cell–mediated lesions. “How does that impact response to targeted therapies?” he asked. “We have no idea. We need to learn that.” He noted that psoriasiform lesions are not limited to Asian patients, but also appear in elderly patients with AD. “They look different [in elderly patients] and they may respond differently; they have more psoriasiform lesions and it’s not exactly clear why.”

Other morphologic variants of AD to be aware of include follicular eczema, xerosis, and the itch-dominant form, which Dr. Silverberg and colleagues addressed in a recently published study. “There are some patients who have milder-looking lesions, but their itch is just out of control,” he said. “This is a pattern that we need to recognize.”

Evolution of disease, symptom severity

Factors to consider for the evolution of disease component of the proposed classification include age of AD onset or disease recurrence, frequency and duration of flares, disease activity between flares, periods of disease clearance, and the overall disease trajectory. “We do get patients who say that every year their disease seems to get worse over time, for reasons that are not always clear,” Dr. Silverberg said.

Assessment tools he recommends for the symptom severity component of DESCRIBE-AD include the patient-reported global AD severity, numerical rating scale (NRS) worst or average itch in the past 7 days, the Skin Pain NRS, and the Sleep Quality NRS, which each take fewer than 30 seconds to complete. “You can have your nurses do this or can you have the patients fill out the form in the waiting area before they see you,” Dr. Silverberg said.

He also advises asking patients about the number of nights they experience sleep disturbance and if they have difficulty falling asleep or have nighttime awakenings because of their AD. Symptoms of anxiety and depression can be assessed with the Hospital Anxiety and Depression Scale and the Patient-Health Questionnaire–9, which each take 2-3 minutes to complete.

Recommended assessment tools for other symptoms – such as bleeding, oozing, and xerosis – include the Patient-Oriented Eczema Measure, which takes 2-3 minutes to complete, and the Atopic Dermatitis Control Tool or the Recap of Atopic Eczema, which each take 2-3 minutes to complete.
 

Comorbid health disorders

Comorbid health disorders linked to AD are varied and include atopic comorbidities such as asthma or wheeze, hay fever or oculonasal symptoms, food allergy, recurrent infections such as herpes simplex virus, mental health disorders, alopecia areata, Th1-mediated comorbidities, and adverse events to medication such as venous thromboembolism, hypertension, and impaired renal or liver function. “All of these are important because if the patients have these at baseline, they may not be good candidates for some therapies that cause these types of side effects,” Dr. Silverberg said.

Response to therapy, intensity of lesions

As for response to therapy, clinicians can ask patients, “How do you feel you’re improving?” But it’s also important to assess the signs, symptoms, frequency of flares, and comorbidities as part of that response to therapy, “and of course the adverse events and treatment burden,” he said.

For the intensity of lesions component of DESCRIBE-AD, Dr. Silverberg said that the Investigator’s Global Assessment–AD is an effective tool for clinical use. “You can also use tools like the Eczema Area and Severity Index or the Scoring AD, but recognize these are challenging,” and can be difficult to use if not well trained to use them, he said. “At the very least, do an Investigator’s Global Assessment and do a body surface area measurement.”

In his opinion, four key signs that should be assessed in clinical trials are erythema, edema/papulation, excoriation, and lichenification/prurigo nodules.
 

Burden of disease

In terms of assessing AD disease burden, guidelines from the American Academy of Dermatology don’t give a specific tool to use, but recommend asking open-ended questions, Dr. Silverberg said. “I would not recommend that, because when you ask an open-ended question, the flood gates open up because most patients are suffering miserably with this disease when it’s uncontrolled.

“That’s why it’s valuable to use structured, validated tools like the Dermatology Life Quality Index and the Patient Reported Outcome Measurement Information System. They don’t take a lot of time to complete, and you can look at the score and determine how burdensome their disease is, even in a busy clinical practice. They’re not going to slow you down; they’re going to speed you up and make you better at your therapeutic decision-making. I can guarantee you that most patients will love you for it. Sometimes patients say to me, ‘you’re the first doctor to ask these questions.’ ”
 

Extent of disease

Finally, for the extent of disease component of DESCRIBE-AD, he emphasized the importance of doing a full-body exam to appreciate the affected body surface area, flexural versus extensor distribution, and involvement and severity of disease on special sites such as the face, hands, feet, genitals, and scalp.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

[email protected]

The heterogeneous clinical course of atopic dermatitis (AD) and its differing signs, symptoms, burden, and response to treatment can pose a quandary for physicians.

This is behind a new classification framework called DESCRIBE-AD, proposed by Jonathan I. Silverberg, MD, PhD, MPH, not only as a way to standardize the assessment of AD in clinical practice – but also to improve the classification of AD in clinical practice and clinical trials, facilitate tailoring of therapy to individual patient characteristics, and better identify therapeutically relevant disease subsets.

Dr. Silverberg, director of clinical research in the department of dermatology at George Washington University, Washington, debuted DESCRIBE-AD during the Revolutionizing Atopic Dermatitis symposium. The “D” in the mnemonic stands for dermatitis morphology and phenotype, the “E” for evolution of disease, the “S” for symptom severity, the “C” for comorbid health disorders, the “R” for response to therapy, the “I” for intensity of lesions, the “B” for burden of disease, and the “E” for extent of lesions.

At the meeting, he discussed the concepts behind each letter of the mnemonic.
 

Dermatitis morphology and phenotype

In the dermatitis morphology and phenotype component of DESCRIBE-AD, “there’s a lot to consider,” he said. “There are chronic signs like lichenification and prurigo nodules, which have treatment ramifications,” such as the length of time patients may need to be treated, and possibly “the use of more potent, targeted options to go after some of these lesions.”

Recent studies suggest that nummular lesions have a different underlying pathogenesis suggesting an overlap between Th2 and Th17 cell–mediated lesions. “How does that impact response to targeted therapies?” he asked. “We have no idea. We need to learn that.” He noted that psoriasiform lesions are not limited to Asian patients, but also appear in elderly patients with AD. “They look different [in elderly patients] and they may respond differently; they have more psoriasiform lesions and it’s not exactly clear why.”

Other morphologic variants of AD to be aware of include follicular eczema, xerosis, and the itch-dominant form, which Dr. Silverberg and colleagues addressed in a recently published study. “There are some patients who have milder-looking lesions, but their itch is just out of control,” he said. “This is a pattern that we need to recognize.”

Evolution of disease, symptom severity

Factors to consider for the evolution of disease component of the proposed classification include age of AD onset or disease recurrence, frequency and duration of flares, disease activity between flares, periods of disease clearance, and the overall disease trajectory. “We do get patients who say that every year their disease seems to get worse over time, for reasons that are not always clear,” Dr. Silverberg said.

Assessment tools he recommends for the symptom severity component of DESCRIBE-AD include the patient-reported global AD severity, numerical rating scale (NRS) worst or average itch in the past 7 days, the Skin Pain NRS, and the Sleep Quality NRS, which each take fewer than 30 seconds to complete. “You can have your nurses do this or can you have the patients fill out the form in the waiting area before they see you,” Dr. Silverberg said.

He also advises asking patients about the number of nights they experience sleep disturbance and if they have difficulty falling asleep or have nighttime awakenings because of their AD. Symptoms of anxiety and depression can be assessed with the Hospital Anxiety and Depression Scale and the Patient-Health Questionnaire–9, which each take 2-3 minutes to complete.

Recommended assessment tools for other symptoms – such as bleeding, oozing, and xerosis – include the Patient-Oriented Eczema Measure, which takes 2-3 minutes to complete, and the Atopic Dermatitis Control Tool or the Recap of Atopic Eczema, which each take 2-3 minutes to complete.
 

Comorbid health disorders

Comorbid health disorders linked to AD are varied and include atopic comorbidities such as asthma or wheeze, hay fever or oculonasal symptoms, food allergy, recurrent infections such as herpes simplex virus, mental health disorders, alopecia areata, Th1-mediated comorbidities, and adverse events to medication such as venous thromboembolism, hypertension, and impaired renal or liver function. “All of these are important because if the patients have these at baseline, they may not be good candidates for some therapies that cause these types of side effects,” Dr. Silverberg said.

Response to therapy, intensity of lesions

As for response to therapy, clinicians can ask patients, “How do you feel you’re improving?” But it’s also important to assess the signs, symptoms, frequency of flares, and comorbidities as part of that response to therapy, “and of course the adverse events and treatment burden,” he said.

For the intensity of lesions component of DESCRIBE-AD, Dr. Silverberg said that the Investigator’s Global Assessment–AD is an effective tool for clinical use. “You can also use tools like the Eczema Area and Severity Index or the Scoring AD, but recognize these are challenging,” and can be difficult to use if not well trained to use them, he said. “At the very least, do an Investigator’s Global Assessment and do a body surface area measurement.”

In his opinion, four key signs that should be assessed in clinical trials are erythema, edema/papulation, excoriation, and lichenification/prurigo nodules.
 

Burden of disease

In terms of assessing AD disease burden, guidelines from the American Academy of Dermatology don’t give a specific tool to use, but recommend asking open-ended questions, Dr. Silverberg said. “I would not recommend that, because when you ask an open-ended question, the flood gates open up because most patients are suffering miserably with this disease when it’s uncontrolled.

“That’s why it’s valuable to use structured, validated tools like the Dermatology Life Quality Index and the Patient Reported Outcome Measurement Information System. They don’t take a lot of time to complete, and you can look at the score and determine how burdensome their disease is, even in a busy clinical practice. They’re not going to slow you down; they’re going to speed you up and make you better at your therapeutic decision-making. I can guarantee you that most patients will love you for it. Sometimes patients say to me, ‘you’re the first doctor to ask these questions.’ ”
 

Extent of disease

Finally, for the extent of disease component of DESCRIBE-AD, he emphasized the importance of doing a full-body exam to appreciate the affected body surface area, flexural versus extensor distribution, and involvement and severity of disease on special sites such as the face, hands, feet, genitals, and scalp.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

[email protected]

Use of metformin was associated with a significant reduction in the risk of developing basal cell carcinoma (BCC), based on data from a population case-control study in Iceland.

“In addition to general anticarcinogenic effects, metformin has also been shown to directly inhibit the sonic hedgehog pathway, a key pathway in basal cell carcinoma (BCC) pathogenesis,” Jonas A. Adalsteinsson, MD, of the University of Iceland, Reykjavik, and colleagues wrote. “The relationship between metformin and keratinocyte carcinoma has not been well-characterized but is of importance considering that metformin is a commonly prescribed medication.”

They added that the hedgehog pathway inhibitors vismodegib (Erivedge) and sonidegib (Odomzo), approved for treating BCC, “are highly effective for BCC prevention, but their broad use for BCC prophylaxis is limited due to numerous side effects.”

In the study, published in the Journal of the American Academy of Dermatology, the researchers identified 6,880 first-time cancer patients with BCC, squamous cell carcinoma in situ (SCCis), or invasive SCC, and 69,620 population controls using data from the Icelandic Cancer Registry and the Icelandic Prescription Medicine Register between 2003 and 2017. Metformin exposure was defined as having filled at least one prescription of metformin more than 2 years prior to cancer diagnosis. They used grams and daily dose units of metformin in their analysis; one DDU of metformin, “or its average daily maintenance dose when used for its primary indication, is 2 grams,” they noted.

Overall, metformin use was associated with a significantly lower risk of developing BCC, compared with nonuse (adjusted odds ratio, 0.71; 95% confidence interval, 0.61-0.83).

The reduced risk occurred similarly across age and gender subgroups, with the exception of individuals younger than 60 years, the researchers said. “This might signify that metformin has less of a protective effect in younger individuals, but we might also have lacked power in this category.” The association with reduced BCC risk remained significant at all three cumulative dose levels measured: 1-500 DDUs, 501-1,500 DDUs, and more than 1,500 DDUs.

Metformin use was not significantly associated with reduced risk of invasive SCC (aOR, 1.01) and in most cases of SCCis. However, the 501-1,500 DDU dose category was associated with a slight increase in risk of SCCis (aOR, 1.40; 95% CI, 1.00-1.96), “showing a possible increased risk of SCCis,” the authors wrote.

The decrease in BCC risk was seen across all metformin dosing levels, but the reason for this remains unclear, and might be related to a confounding factor that was not considered in this study, the researchers said. “It could also be that metformin’s BCC risk-lowering effect is immediate, with only a low dose being needed to see a clinical benefit.”

The study findings were limited by several factors, including the retrospective design and the inability to adjust for factors including ultraviolet exposure, Fitzpatrick skin type, and comorbidities. The frequent use of metformin by people with type 2 diabetes suggests diabetes itself or other diabetes medications could be possible confounding factors, the researchers wrote.

However, the results were strengthened by the large study population, and the data suggest an association between reduced risk of first-time BCC and metformin use, they added.

“Randomized, prospective trials are required to fully understand the effect metformin has on BCC and SCC risk,” the researchers concluded.

“There is a dire need to reduce incidence of skin cancers in general, and consequently a need for new non-surgical treatment options for keratinocytic nonmelanoma skin cancers,” Amor Khachemoune, MD, a dermatologist at the State University of New York, Brooklyn, and the department of dermatology of the Veteran Affairs NY Harbor Healthcare System, also in Brooklyn, said in an interview.

Dr. Khachemoune, who was not involved with the study, said that he was not surprised by the findings. “Like other well-studied sonic hedgehog inhibitors, vismodegib and sonidegib, metformin has a demonstrated effect on this pathway. The medical community outside of dermatology has extensive experience with the use of metformin for a host of other indications, including its role as anticarcinogenic, so it seemed natural that one would consider widening its use to quell the ever-expanding cases of basal cell carcinomas.”

However, complications from long-term use, though likely rare, could be a limitation in using metformin as a chemoprotective agent, Dr. Khachemoune said. Metformin-associated lactic acidosis is one example of a rare, but potentially life-threatening adverse event.

“Finding the right dosage and having an algorithm for follow up monitoring of side effects would certainly need to be put in place in a standardized way,” he emphasized. “As stated by the authors of this study, more inclusive research involving other groups with nonkeratinocytic malignancies in larger cohorts is needed.”

The study received no outside funding. The researchers and Dr. Khachemoune had no financial conflicts to disclose.

Use of metformin was associated with a significant reduction in the risk of developing basal cell carcinoma (BCC), based on data from a population case-control study in Iceland.

“In addition to general anticarcinogenic effects, metformin has also been shown to directly inhibit the sonic hedgehog pathway, a key pathway in basal cell carcinoma (BCC) pathogenesis,” Jonas A. Adalsteinsson, MD, of the University of Iceland, Reykjavik, and colleagues wrote. “The relationship between metformin and keratinocyte carcinoma has not been well-characterized but is of importance considering that metformin is a commonly prescribed medication.”

They added that the hedgehog pathway inhibitors vismodegib (Erivedge) and sonidegib (Odomzo), approved for treating BCC, “are highly effective for BCC prevention, but their broad use for BCC prophylaxis is limited due to numerous side effects.”

In the study, published in the Journal of the American Academy of Dermatology, the researchers identified 6,880 first-time cancer patients with BCC, squamous cell carcinoma in situ (SCCis), or invasive SCC, and 69,620 population controls using data from the Icelandic Cancer Registry and the Icelandic Prescription Medicine Register between 2003 and 2017. Metformin exposure was defined as having filled at least one prescription of metformin more than 2 years prior to cancer diagnosis. They used grams and daily dose units of metformin in their analysis; one DDU of metformin, “or its average daily maintenance dose when used for its primary indication, is 2 grams,” they noted.

Overall, metformin use was associated with a significantly lower risk of developing BCC, compared with nonuse (adjusted odds ratio, 0.71; 95% confidence interval, 0.61-0.83).

The reduced risk occurred similarly across age and gender subgroups, with the exception of individuals younger than 60 years, the researchers said. “This might signify that metformin has less of a protective effect in younger individuals, but we might also have lacked power in this category.” The association with reduced BCC risk remained significant at all three cumulative dose levels measured: 1-500 DDUs, 501-1,500 DDUs, and more than 1,500 DDUs.

Metformin use was not significantly associated with reduced risk of invasive SCC (aOR, 1.01) and in most cases of SCCis. However, the 501-1,500 DDU dose category was associated with a slight increase in risk of SCCis (aOR, 1.40; 95% CI, 1.00-1.96), “showing a possible increased risk of SCCis,” the authors wrote.

The decrease in BCC risk was seen across all metformin dosing levels, but the reason for this remains unclear, and might be related to a confounding factor that was not considered in this study, the researchers said. “It could also be that metformin’s BCC risk-lowering effect is immediate, with only a low dose being needed to see a clinical benefit.”

The study findings were limited by several factors, including the retrospective design and the inability to adjust for factors including ultraviolet exposure, Fitzpatrick skin type, and comorbidities. The frequent use of metformin by people with type 2 diabetes suggests diabetes itself or other diabetes medications could be possible confounding factors, the researchers wrote.

However, the results were strengthened by the large study population, and the data suggest an association between reduced risk of first-time BCC and metformin use, they added.

“Randomized, prospective trials are required to fully understand the effect metformin has on BCC and SCC risk,” the researchers concluded.

“There is a dire need to reduce incidence of skin cancers in general, and consequently a need for new non-surgical treatment options for keratinocytic nonmelanoma skin cancers,” Amor Khachemoune, MD, a dermatologist at the State University of New York, Brooklyn, and the department of dermatology of the Veteran Affairs NY Harbor Healthcare System, also in Brooklyn, said in an interview.

Dr. Khachemoune, who was not involved with the study, said that he was not surprised by the findings. “Like other well-studied sonic hedgehog inhibitors, vismodegib and sonidegib, metformin has a demonstrated effect on this pathway. The medical community outside of dermatology has extensive experience with the use of metformin for a host of other indications, including its role as anticarcinogenic, so it seemed natural that one would consider widening its use to quell the ever-expanding cases of basal cell carcinomas.”

However, complications from long-term use, though likely rare, could be a limitation in using metformin as a chemoprotective agent, Dr. Khachemoune said. Metformin-associated lactic acidosis is one example of a rare, but potentially life-threatening adverse event.

“Finding the right dosage and having an algorithm for follow up monitoring of side effects would certainly need to be put in place in a standardized way,” he emphasized. “As stated by the authors of this study, more inclusive research involving other groups with nonkeratinocytic malignancies in larger cohorts is needed.”

The study received no outside funding. The researchers and Dr. Khachemoune had no financial conflicts to disclose.

Use of metformin was associated with a significant reduction in the risk of developing basal cell carcinoma (BCC), based on data from a population case-control study in Iceland.

“In addition to general anticarcinogenic effects, metformin has also been shown to directly inhibit the sonic hedgehog pathway, a key pathway in basal cell carcinoma (BCC) pathogenesis,” Jonas A. Adalsteinsson, MD, of the University of Iceland, Reykjavik, and colleagues wrote. “The relationship between metformin and keratinocyte carcinoma has not been well-characterized but is of importance considering that metformin is a commonly prescribed medication.”

They added that the hedgehog pathway inhibitors vismodegib (Erivedge) and sonidegib (Odomzo), approved for treating BCC, “are highly effective for BCC prevention, but their broad use for BCC prophylaxis is limited due to numerous side effects.”

In the study, published in the Journal of the American Academy of Dermatology, the researchers identified 6,880 first-time cancer patients with BCC, squamous cell carcinoma in situ (SCCis), or invasive SCC, and 69,620 population controls using data from the Icelandic Cancer Registry and the Icelandic Prescription Medicine Register between 2003 and 2017. Metformin exposure was defined as having filled at least one prescription of metformin more than 2 years prior to cancer diagnosis. They used grams and daily dose units of metformin in their analysis; one DDU of metformin, “or its average daily maintenance dose when used for its primary indication, is 2 grams,” they noted.

Overall, metformin use was associated with a significantly lower risk of developing BCC, compared with nonuse (adjusted odds ratio, 0.71; 95% confidence interval, 0.61-0.83).

The reduced risk occurred similarly across age and gender subgroups, with the exception of individuals younger than 60 years, the researchers said. “This might signify that metformin has less of a protective effect in younger individuals, but we might also have lacked power in this category.” The association with reduced BCC risk remained significant at all three cumulative dose levels measured: 1-500 DDUs, 501-1,500 DDUs, and more than 1,500 DDUs.

Metformin use was not significantly associated with reduced risk of invasive SCC (aOR, 1.01) and in most cases of SCCis. However, the 501-1,500 DDU dose category was associated with a slight increase in risk of SCCis (aOR, 1.40; 95% CI, 1.00-1.96), “showing a possible increased risk of SCCis,” the authors wrote.

The decrease in BCC risk was seen across all metformin dosing levels, but the reason for this remains unclear, and might be related to a confounding factor that was not considered in this study, the researchers said. “It could also be that metformin’s BCC risk-lowering effect is immediate, with only a low dose being needed to see a clinical benefit.”

The study findings were limited by several factors, including the retrospective design and the inability to adjust for factors including ultraviolet exposure, Fitzpatrick skin type, and comorbidities. The frequent use of metformin by people with type 2 diabetes suggests diabetes itself or other diabetes medications could be possible confounding factors, the researchers wrote.

However, the results were strengthened by the large study population, and the data suggest an association between reduced risk of first-time BCC and metformin use, they added.

“Randomized, prospective trials are required to fully understand the effect metformin has on BCC and SCC risk,” the researchers concluded.

“There is a dire need to reduce incidence of skin cancers in general, and consequently a need for new non-surgical treatment options for keratinocytic nonmelanoma skin cancers,” Amor Khachemoune, MD, a dermatologist at the State University of New York, Brooklyn, and the department of dermatology of the Veteran Affairs NY Harbor Healthcare System, also in Brooklyn, said in an interview.

Dr. Khachemoune, who was not involved with the study, said that he was not surprised by the findings. “Like other well-studied sonic hedgehog inhibitors, vismodegib and sonidegib, metformin has a demonstrated effect on this pathway. The medical community outside of dermatology has extensive experience with the use of metformin for a host of other indications, including its role as anticarcinogenic, so it seemed natural that one would consider widening its use to quell the ever-expanding cases of basal cell carcinomas.”

However, complications from long-term use, though likely rare, could be a limitation in using metformin as a chemoprotective agent, Dr. Khachemoune said. Metformin-associated lactic acidosis is one example of a rare, but potentially life-threatening adverse event.

“Finding the right dosage and having an algorithm for follow up monitoring of side effects would certainly need to be put in place in a standardized way,” he emphasized. “As stated by the authors of this study, more inclusive research involving other groups with nonkeratinocytic malignancies in larger cohorts is needed.”

The study received no outside funding. The researchers and Dr. Khachemoune had no financial conflicts to disclose.

The Food and Drug Administration has approved pembrolizumab (Keytruda) monotherapy for locally advanced cutaneous squamous cell carcinoma (cSCC) that can’t be cured by surgery or radiation.

The July 6 approval for the programmed death–1 inhibitor follows a June FDA approval for pembrolizumab monotherapy in patients with recurrent or metastatic cSCC disease not curable by surgery or radiation. Both approvals, pembrolizumab’s first for cSCC, are based on findings from the second interim analysis of the phase 2, multicenter, open-label KEYNOTE-629 trial.

The objective response rate in the cohort of 54 patients with locally advanced disease was 50%, including a complete response rate of 17% and a partial response rate of 33%. Duration of response was 6 months or longer in 81% of the 27 responders, and 12 months or longer in 37% of responders. After a median follow-up of 13.4 months, median duration of response had not yet been reached.

Pembrolizumab has previously received FDA approvals, either as monotherapy or in combination with other agents, for the treatment of numerous cancer types, including certain melanomas, non–small cell lung cancers, head and neck SCCs, classical Hodgkin lymphomas, primary mediastinal large B-cell lymphomas, urothelial carcinomas, microsatellite instability–high or mismatch repair–deficient cancers, and gastric, esophageal, cervical, hepatocellular, Merkel cell, renal cell, tumor mutational burden–high, and triple-negative breast cancers.

Patients in the KEYNOTE-629 trial received pembrolizumab at a dose of 200 mg IV every 3 weeks for 24 months or until documented disease progression or unacceptable toxicity.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC in KEYNOTE-629 were similar to those observed in patients with melanoma or non–small cell lung cancer who were treated with pembrolizumab monotherapy in previous trials.

The checkpoint inhibitor can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation,” Merck explained in a press release, noting that “early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda.”

Depending on the severity of any reaction, treatment should be withheld or permanently discontinued, and corticosteroids administered if appropriate, Merck stated.

[email protected]

The Food and Drug Administration has approved pembrolizumab (Keytruda) monotherapy for locally advanced cutaneous squamous cell carcinoma (cSCC) that can’t be cured by surgery or radiation.

The July 6 approval for the programmed death–1 inhibitor follows a June FDA approval for pembrolizumab monotherapy in patients with recurrent or metastatic cSCC disease not curable by surgery or radiation. Both approvals, pembrolizumab’s first for cSCC, are based on findings from the second interim analysis of the phase 2, multicenter, open-label KEYNOTE-629 trial.

The objective response rate in the cohort of 54 patients with locally advanced disease was 50%, including a complete response rate of 17% and a partial response rate of 33%. Duration of response was 6 months or longer in 81% of the 27 responders, and 12 months or longer in 37% of responders. After a median follow-up of 13.4 months, median duration of response had not yet been reached.

Pembrolizumab has previously received FDA approvals, either as monotherapy or in combination with other agents, for the treatment of numerous cancer types, including certain melanomas, non–small cell lung cancers, head and neck SCCs, classical Hodgkin lymphomas, primary mediastinal large B-cell lymphomas, urothelial carcinomas, microsatellite instability–high or mismatch repair–deficient cancers, and gastric, esophageal, cervical, hepatocellular, Merkel cell, renal cell, tumor mutational burden–high, and triple-negative breast cancers.

Patients in the KEYNOTE-629 trial received pembrolizumab at a dose of 200 mg IV every 3 weeks for 24 months or until documented disease progression or unacceptable toxicity.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC in KEYNOTE-629 were similar to those observed in patients with melanoma or non–small cell lung cancer who were treated with pembrolizumab monotherapy in previous trials.

The checkpoint inhibitor can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation,” Merck explained in a press release, noting that “early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda.”

Depending on the severity of any reaction, treatment should be withheld or permanently discontinued, and corticosteroids administered if appropriate, Merck stated.

[email protected]

The Food and Drug Administration has approved pembrolizumab (Keytruda) monotherapy for locally advanced cutaneous squamous cell carcinoma (cSCC) that can’t be cured by surgery or radiation.

The July 6 approval for the programmed death–1 inhibitor follows a June FDA approval for pembrolizumab monotherapy in patients with recurrent or metastatic cSCC disease not curable by surgery or radiation. Both approvals, pembrolizumab’s first for cSCC, are based on findings from the second interim analysis of the phase 2, multicenter, open-label KEYNOTE-629 trial.

The objective response rate in the cohort of 54 patients with locally advanced disease was 50%, including a complete response rate of 17% and a partial response rate of 33%. Duration of response was 6 months or longer in 81% of the 27 responders, and 12 months or longer in 37% of responders. After a median follow-up of 13.4 months, median duration of response had not yet been reached.

Pembrolizumab has previously received FDA approvals, either as monotherapy or in combination with other agents, for the treatment of numerous cancer types, including certain melanomas, non–small cell lung cancers, head and neck SCCs, classical Hodgkin lymphomas, primary mediastinal large B-cell lymphomas, urothelial carcinomas, microsatellite instability–high or mismatch repair–deficient cancers, and gastric, esophageal, cervical, hepatocellular, Merkel cell, renal cell, tumor mutational burden–high, and triple-negative breast cancers.

Patients in the KEYNOTE-629 trial received pembrolizumab at a dose of 200 mg IV every 3 weeks for 24 months or until documented disease progression or unacceptable toxicity.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC in KEYNOTE-629 were similar to those observed in patients with melanoma or non–small cell lung cancer who were treated with pembrolizumab monotherapy in previous trials.

The checkpoint inhibitor can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation,” Merck explained in a press release, noting that “early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda.”

Depending on the severity of any reaction, treatment should be withheld or permanently discontinued, and corticosteroids administered if appropriate, Merck stated.

[email protected]

People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.

The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.

The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.

“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.

“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”

Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.

Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.

Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.

All participants had low neutralizing titers against the alpha (B.1.1.7) variant.

The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”

A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.

‘Some protection is better than none’

These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.

It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.

“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.

“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.

“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
 

Temporarily stopping methotrexate

It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.

Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.

“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”

Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.

However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.

This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.

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

People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.

The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.

The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.

“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.

“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”

Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.

Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.

Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.

All participants had low neutralizing titers against the alpha (B.1.1.7) variant.

The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”

A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.

‘Some protection is better than none’

These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.

It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.

“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.

“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.

“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
 

Temporarily stopping methotrexate

It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.

Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.

“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”

Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.

However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.

This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.

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

People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.

The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.

The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.

“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.

“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”

Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.

Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.

Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.

All participants had low neutralizing titers against the alpha (B.1.1.7) variant.

The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”

A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.

‘Some protection is better than none’

These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.

It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.

“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.

“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.

“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
 

Temporarily stopping methotrexate

It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.

Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.

“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”

Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.

However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.

This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.

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

Salary disparities persist in academic internal medicine specialties and are most obvious in procedural specialties, such as cardiology, in which there are fewer women, research suggests.

“Substantial salary inequities persist at the highest faculty levels and specifically in procedural-based specialties,” Teresa Wang, MD, and colleagues reported in a research letter published online July 12, 2021, in JAMA Internal Medicine.

To examine the demographics and salaries of academic internal medicine physician specialists, Dr. Wang, who is with the division of cardiovascular medicine at the University of Pennsylvania, Philadelphia, and coauthors analyzed survey results from faculty at 154 U.S. medical schools.

They used data from the Association of American Medical Colleges Faculty Salary Report of 2018-2019 to assess the median annual salary, faculty rank, and gender for 21,905 faculty in 13 internal medicine specialties.

Overall, women made up less than 40% of full-time faculty across ranks. Female representation was approximately equal at the instructor and assistant ranks – 47% and 46%, respectively – but decreased to 24% at the professor level.

The authors found that women made up the majority in three specialties – general internal medicine, endocrinology, and geriatrics. In contrast, women were least represented in the procedural specialties of pulmonology, critical/intensive care, gastroenterology, and cardiology.

The greatest imbalance was in cardiology, in which only 21% were women, the researchers noted.

Across faculty ranks, the median annual salary was less for women than for men. The median salary for women was within $25,000 of that for men at all ranks except chief and was at least 90% of that for men in 10 of 13 internal medicine specialties.

Cardiology, gastroenterology, and critical/intensive care were the three specialties in which women’s median salary did not reach 90% of men’s. These specialties tended to be better paid overall, “but also demonstrated the largest gender disparities in both representation and salary, particularly within the higher ranks of cardiology and gastroenterology,” the researchers said.

The reasons for gender disparities are unclear, though internal medicine procedural specialties “have long been male dominated in composition and leadership,” the authors noted. The findings indicate that workforce gender parity may be associated with salary equity.

“Despite the growing awareness of workforce disparities in medicine, our findings suggest that women internal medicine specialists remain underpaid and are not promoted to senior level academic ranks when compared with career trajectories of their male counterparts,” study author Nosheen Reza, MD, of the division of cardiovascular medicine at the University of Pennsylvania, told this news organization.

The researchers noted that they were unable to adjust at the individual level for various factors that may influence salary, such as professional service, academic productivity, clinical volume, and supplementary funding sources, and that the results might not apply to all U.S. medical schools, in which departmental structures vary.

Procedures versus evaluation and management

Still, the research “provides an interesting snapshot of current salary disparities in academic internal medicine,” comment Rita F. Redberg, MD, and colleagues in a related editorial. Dr. Redberg, the editor of JAMA Internal Medicine, is affiliated with the department of medicine at the University of California, San Francisco.

Internal medicine has 13 specialties and dozens of subspecialties, and “procedural subspecialties are more male dominated and better paid than nonprocedural subspecialties – both topics deserving of further exploration,” the editorialists wrote.

The field needs to address various issues that drive some women to “shun male-dominated procedural-based fields – including lack of role models, macho ‘cowboy’ culture, unpredictable schedules, longer training periods, or cultural factors,” Dr. Redberg and coauthors suggested. “Concurrently, the medical profession overall, as well as specialties, should thoughtfully and frequently reassess how to distribute pay more equitably and to remove the premium currently paid for procedures over evaluation and management services.”

“Unfortunately, it is not a surprise that there continues to be a gender gap for salary in academic medicine,” Dr. Redberg said in an interview. “It was interesting to see that gender pay disparities were greatest in the procedure-intensive specialties, and we do know that procedures are much more highly reimbursed than evaluation and management time, even in the IM specialties. From a patient perspective, I think what they value most highly is having their doctor talk with them and explain treatment options and risks and benefits. Sadly, our fee-for-service–based reimbursement system values procedures more highly than talking with patients. And part of the gender gap in salary is attributed to less women being proceduralists.”

The Medicare Payment Advisory Commission “has made some excellent recommendations to Congress on helping to correct this imbalance,” Dr. Redberg added.

In a separate viewpoint article, Leah M. Marcotte, MD, of the department of medicine at the University of Washington, Seattle, and colleagues describe reasons why women physicians may have “slower promotional time lines,” compared with men, such as receiving fewer and smaller grants, being underrepresented as speakers at national conferences, and receiving fewer invitations to author editorials.

“To narrow this gap, institutions should proactively nominate women, with a greater focus on those underrepresented in medicine, for internal and external awards and speaking opportunities,” Dr. Marcotte and coauthors wrote. “Institutions should adopt policies to cover child care, breastfeeding/pumping accommodations, and dependent travel. Academic departments should continue to offer virtual speaking opportunities even after COVID-19 pandemic travel restrictions become unnecessary.”

Institutions can also assist women faculty in preparing promotion dossiers.

“Gender disparities in promotion in academic medicine have been described for decades, and yet progress to close the gap has been untenably slow,” they said. “Rather than expecting faculty to adapt to existing systems, we need to change the promotion process to work better for all.”

The authors disclosed no relevant financial relationships. Dr. Redberg has received grants from Arnold Ventures, the Greenwall Foundation, and the National Heart, Lung, and Blood Institute outside the submitted work. One viewpoint coauthor has received honoraria from the American Board of Internal Medicine, and another has received personal fees from F-Prime Capital, both outside the submitted work.

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

Salary disparities persist in academic internal medicine specialties and are most obvious in procedural specialties, such as cardiology, in which there are fewer women, research suggests.

“Substantial salary inequities persist at the highest faculty levels and specifically in procedural-based specialties,” Teresa Wang, MD, and colleagues reported in a research letter published online July 12, 2021, in JAMA Internal Medicine.

To examine the demographics and salaries of academic internal medicine physician specialists, Dr. Wang, who is with the division of cardiovascular medicine at the University of Pennsylvania, Philadelphia, and coauthors analyzed survey results from faculty at 154 U.S. medical schools.

They used data from the Association of American Medical Colleges Faculty Salary Report of 2018-2019 to assess the median annual salary, faculty rank, and gender for 21,905 faculty in 13 internal medicine specialties.

Overall, women made up less than 40% of full-time faculty across ranks. Female representation was approximately equal at the instructor and assistant ranks – 47% and 46%, respectively – but decreased to 24% at the professor level.

The authors found that women made up the majority in three specialties – general internal medicine, endocrinology, and geriatrics. In contrast, women were least represented in the procedural specialties of pulmonology, critical/intensive care, gastroenterology, and cardiology.

The greatest imbalance was in cardiology, in which only 21% were women, the researchers noted.

Across faculty ranks, the median annual salary was less for women than for men. The median salary for women was within $25,000 of that for men at all ranks except chief and was at least 90% of that for men in 10 of 13 internal medicine specialties.

Cardiology, gastroenterology, and critical/intensive care were the three specialties in which women’s median salary did not reach 90% of men’s. These specialties tended to be better paid overall, “but also demonstrated the largest gender disparities in both representation and salary, particularly within the higher ranks of cardiology and gastroenterology,” the researchers said.

The reasons for gender disparities are unclear, though internal medicine procedural specialties “have long been male dominated in composition and leadership,” the authors noted. The findings indicate that workforce gender parity may be associated with salary equity.

“Despite the growing awareness of workforce disparities in medicine, our findings suggest that women internal medicine specialists remain underpaid and are not promoted to senior level academic ranks when compared with career trajectories of their male counterparts,” study author Nosheen Reza, MD, of the division of cardiovascular medicine at the University of Pennsylvania, told this news organization.

The researchers noted that they were unable to adjust at the individual level for various factors that may influence salary, such as professional service, academic productivity, clinical volume, and supplementary funding sources, and that the results might not apply to all U.S. medical schools, in which departmental structures vary.

Procedures versus evaluation and management

Still, the research “provides an interesting snapshot of current salary disparities in academic internal medicine,” comment Rita F. Redberg, MD, and colleagues in a related editorial. Dr. Redberg, the editor of JAMA Internal Medicine, is affiliated with the department of medicine at the University of California, San Francisco.

Internal medicine has 13 specialties and dozens of subspecialties, and “procedural subspecialties are more male dominated and better paid than nonprocedural subspecialties – both topics deserving of further exploration,” the editorialists wrote.

The field needs to address various issues that drive some women to “shun male-dominated procedural-based fields – including lack of role models, macho ‘cowboy’ culture, unpredictable schedules, longer training periods, or cultural factors,” Dr. Redberg and coauthors suggested. “Concurrently, the medical profession overall, as well as specialties, should thoughtfully and frequently reassess how to distribute pay more equitably and to remove the premium currently paid for procedures over evaluation and management services.”

“Unfortunately, it is not a surprise that there continues to be a gender gap for salary in academic medicine,” Dr. Redberg said in an interview. “It was interesting to see that gender pay disparities were greatest in the procedure-intensive specialties, and we do know that procedures are much more highly reimbursed than evaluation and management time, even in the IM specialties. From a patient perspective, I think what they value most highly is having their doctor talk with them and explain treatment options and risks and benefits. Sadly, our fee-for-service–based reimbursement system values procedures more highly than talking with patients. And part of the gender gap in salary is attributed to less women being proceduralists.”

The Medicare Payment Advisory Commission “has made some excellent recommendations to Congress on helping to correct this imbalance,” Dr. Redberg added.

In a separate viewpoint article, Leah M. Marcotte, MD, of the department of medicine at the University of Washington, Seattle, and colleagues describe reasons why women physicians may have “slower promotional time lines,” compared with men, such as receiving fewer and smaller grants, being underrepresented as speakers at national conferences, and receiving fewer invitations to author editorials.

“To narrow this gap, institutions should proactively nominate women, with a greater focus on those underrepresented in medicine, for internal and external awards and speaking opportunities,” Dr. Marcotte and coauthors wrote. “Institutions should adopt policies to cover child care, breastfeeding/pumping accommodations, and dependent travel. Academic departments should continue to offer virtual speaking opportunities even after COVID-19 pandemic travel restrictions become unnecessary.”

Institutions can also assist women faculty in preparing promotion dossiers.

“Gender disparities in promotion in academic medicine have been described for decades, and yet progress to close the gap has been untenably slow,” they said. “Rather than expecting faculty to adapt to existing systems, we need to change the promotion process to work better for all.”

The authors disclosed no relevant financial relationships. Dr. Redberg has received grants from Arnold Ventures, the Greenwall Foundation, and the National Heart, Lung, and Blood Institute outside the submitted work. One viewpoint coauthor has received honoraria from the American Board of Internal Medicine, and another has received personal fees from F-Prime Capital, both outside the submitted work.

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

Salary disparities persist in academic internal medicine specialties and are most obvious in procedural specialties, such as cardiology, in which there are fewer women, research suggests.

“Substantial salary inequities persist at the highest faculty levels and specifically in procedural-based specialties,” Teresa Wang, MD, and colleagues reported in a research letter published online July 12, 2021, in JAMA Internal Medicine.

To examine the demographics and salaries of academic internal medicine physician specialists, Dr. Wang, who is with the division of cardiovascular medicine at the University of Pennsylvania, Philadelphia, and coauthors analyzed survey results from faculty at 154 U.S. medical schools.

They used data from the Association of American Medical Colleges Faculty Salary Report of 2018-2019 to assess the median annual salary, faculty rank, and gender for 21,905 faculty in 13 internal medicine specialties.

Overall, women made up less than 40% of full-time faculty across ranks. Female representation was approximately equal at the instructor and assistant ranks – 47% and 46%, respectively – but decreased to 24% at the professor level.

The authors found that women made up the majority in three specialties – general internal medicine, endocrinology, and geriatrics. In contrast, women were least represented in the procedural specialties of pulmonology, critical/intensive care, gastroenterology, and cardiology.

The greatest imbalance was in cardiology, in which only 21% were women, the researchers noted.

Across faculty ranks, the median annual salary was less for women than for men. The median salary for women was within $25,000 of that for men at all ranks except chief and was at least 90% of that for men in 10 of 13 internal medicine specialties.

Cardiology, gastroenterology, and critical/intensive care were the three specialties in which women’s median salary did not reach 90% of men’s. These specialties tended to be better paid overall, “but also demonstrated the largest gender disparities in both representation and salary, particularly within the higher ranks of cardiology and gastroenterology,” the researchers said.

The reasons for gender disparities are unclear, though internal medicine procedural specialties “have long been male dominated in composition and leadership,” the authors noted. The findings indicate that workforce gender parity may be associated with salary equity.

“Despite the growing awareness of workforce disparities in medicine, our findings suggest that women internal medicine specialists remain underpaid and are not promoted to senior level academic ranks when compared with career trajectories of their male counterparts,” study author Nosheen Reza, MD, of the division of cardiovascular medicine at the University of Pennsylvania, told this news organization.

The researchers noted that they were unable to adjust at the individual level for various factors that may influence salary, such as professional service, academic productivity, clinical volume, and supplementary funding sources, and that the results might not apply to all U.S. medical schools, in which departmental structures vary.

Procedures versus evaluation and management

Still, the research “provides an interesting snapshot of current salary disparities in academic internal medicine,” comment Rita F. Redberg, MD, and colleagues in a related editorial. Dr. Redberg, the editor of JAMA Internal Medicine, is affiliated with the department of medicine at the University of California, San Francisco.

Internal medicine has 13 specialties and dozens of subspecialties, and “procedural subspecialties are more male dominated and better paid than nonprocedural subspecialties – both topics deserving of further exploration,” the editorialists wrote.

The field needs to address various issues that drive some women to “shun male-dominated procedural-based fields – including lack of role models, macho ‘cowboy’ culture, unpredictable schedules, longer training periods, or cultural factors,” Dr. Redberg and coauthors suggested. “Concurrently, the medical profession overall, as well as specialties, should thoughtfully and frequently reassess how to distribute pay more equitably and to remove the premium currently paid for procedures over evaluation and management services.”

“Unfortunately, it is not a surprise that there continues to be a gender gap for salary in academic medicine,” Dr. Redberg said in an interview. “It was interesting to see that gender pay disparities were greatest in the procedure-intensive specialties, and we do know that procedures are much more highly reimbursed than evaluation and management time, even in the IM specialties. From a patient perspective, I think what they value most highly is having their doctor talk with them and explain treatment options and risks and benefits. Sadly, our fee-for-service–based reimbursement system values procedures more highly than talking with patients. And part of the gender gap in salary is attributed to less women being proceduralists.”

The Medicare Payment Advisory Commission “has made some excellent recommendations to Congress on helping to correct this imbalance,” Dr. Redberg added.

In a separate viewpoint article, Leah M. Marcotte, MD, of the department of medicine at the University of Washington, Seattle, and colleagues describe reasons why women physicians may have “slower promotional time lines,” compared with men, such as receiving fewer and smaller grants, being underrepresented as speakers at national conferences, and receiving fewer invitations to author editorials.

“To narrow this gap, institutions should proactively nominate women, with a greater focus on those underrepresented in medicine, for internal and external awards and speaking opportunities,” Dr. Marcotte and coauthors wrote. “Institutions should adopt policies to cover child care, breastfeeding/pumping accommodations, and dependent travel. Academic departments should continue to offer virtual speaking opportunities even after COVID-19 pandemic travel restrictions become unnecessary.”

Institutions can also assist women faculty in preparing promotion dossiers.

“Gender disparities in promotion in academic medicine have been described for decades, and yet progress to close the gap has been untenably slow,” they said. “Rather than expecting faculty to adapt to existing systems, we need to change the promotion process to work better for all.”

The authors disclosed no relevant financial relationships. Dr. Redberg has received grants from Arnold Ventures, the Greenwall Foundation, and the National Heart, Lung, and Blood Institute outside the submitted work. One viewpoint coauthor has received honoraria from the American Board of Internal Medicine, and another has received personal fees from F-Prime Capital, both outside the submitted work.

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

Compared with oral propranolol for the treatment of infantile hemangiomas, oral nadolol resulted in faster and greater size involution and color resolution with a similar safety profile out to 52 weeks, results from a prospective analysis of 71 patients showed.

“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”

Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”

Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.

At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).

According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).

The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.

“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.

In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”

They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”

Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.

The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.

[email protected]

Compared with oral propranolol for the treatment of infantile hemangiomas, oral nadolol resulted in faster and greater size involution and color resolution with a similar safety profile out to 52 weeks, results from a prospective analysis of 71 patients showed.

“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”

Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”

Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.

At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).

According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).

The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.

“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.

In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”

They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”

Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.

The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.

[email protected]

Compared with oral propranolol for the treatment of infantile hemangiomas, oral nadolol resulted in faster and greater size involution and color resolution with a similar safety profile out to 52 weeks, results from a prospective analysis of 71 patients showed.

“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”

Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”

Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.

At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).

According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).

The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.

“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.

In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”

They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”

Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.

The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.

[email protected]

Acne & Rosacea

• Rosacea phenotypes
• Erythema and flushing
• Aggressive treatment of acne
• Energy-based rosacea therapy
• Diet and acne

Acne & Rosacea

• Rosacea phenotypes
• Erythema and flushing
• Aggressive treatment of acne
• Energy-based rosacea therapy
• Diet and acne

Acne & Rosacea

• Rosacea phenotypes
• Erythema and flushing
• Aggressive treatment of acne
• Energy-based rosacea therapy
• Diet and acne