The Diagnosis: Sclerosing Perineurioma 

Sclerosing perineurioma, first described in 1997 by Fetsch and Miettinen,¹ is a subtype of perineurioma with a strong predilection for the fingers and palms of young adults. Rare cases involving extra-acral sites including the forearm, elbow, axilla, back, neck, lower leg, thigh, knee, lips, nose, and mouth have been reported.^2-4 Perineurioma is a relatively uncommon and benign peripheral nerve sheath tumor with exclusive perineurial differentiation.⁵ Perineurioma is divided into intraneural and extraneural types; the latter are further subclassified into soft tissue, sclerosing, reticular, and plexiform types. Other rare forms include the sclerosing, Pacinian corpuscle-like perineurioma, lipomatous perineurioma, perineurioma with xanthomatous areas, and perineurioma with granular cells.^6,7  

Clinically, sclerosing perineurioma usually presents as a solitary lesion; however, rare cases of multiple lesions have been reported.⁸ Our patient presented with a solitary papule on the nose. Histopathologically, sclerosing perineurioma demonstrates slender spindle cells in a whorled growth pattern (onion skin) embedded in a hyalinized, lamellar, and dense collagenous stroma with intervening cleftlike spaces. Immunohistochemically, the spindle cells of our case stained positive for epithelial membrane antigen (quiz images). Other positive immunostains for perineurioma include claudin-1 and glucose transporter 1 (GLUT1). Perineurioma lacks expression of S-100 but can express CD34.² As a benign tumor, the prognosis of sclerosing perineurioma is excellent. Complete local excision is considered curative.¹  

Angiofibroma, also known as fibrous papule, is a common and benign lesion located primarily on or in close proximity to the nose.⁹ Angiofibromas can be associated with genodermatoses such as tuberous sclerosis, multiple endocrine neoplasia type 1, or Birt-Hogg-Dubé syndrome. When angiofibromas involve the penis, they are called pearly penile papules. Ungual angiofibroma, also known as Koenen tumor, occurs underneath the nail.^10-12 Both facial angiofibromas (>3) and ungual angiofibromas (>2) are independent major criteria for tuberous sclerosis.¹³ Clinically, angiofibroma presents as a small, dome-shaped, pink papule arising on the lower portion of the nose or nearby area of the central face. Histopathologically, angiofibromas classically demonstrate increased dilated vessels and fibrosis in the dermis. Stellate, plump, spindle-shaped, and multinucleated cells can be seen in the collagenous stroma. The collagen fibers around hair follicles are arranged concentrically, resulting in an onion skin-like appearance. The epidermal rete ridges can be effaced (Figure 1). Increased numbers of single-unit melanocytes along the dermoepidermal junction can be seen in some cases. Immunohistochemically, a variable number of spindled and multinucleated cells in the dermis stain with factor XIIIa. There are at least 7 histologic variants of angiofibroma including hypercellular, pigmented, inflammatory, pleomorphic, clear cell, granular cell, and epithelioid.^9,14 

Palisaded encapsulated neuroma, also referred to as solitary circumscribed neuroma, was first described by Reed et al²¹ in 1972. It is a benign and solitary, firm, dome-shaped, flesh-colored papule that occurs in middle-aged adults, predominately near mucocutaneous junctions of the face. Other locations include the oral mucosa, eyelid, nasal fossa, shoulder, arm, hand, foot, and glans penis.^22,23 Histopathologically, palisaded encapsulated neuroma demonstrates a solitary, well-circumscribed, partially encapsulated, intradermal nodule composed of interweaving fascicles of spindle cells with prominent clefts (Figure 3). Rarely, palisaded encapsulated neuroma may have a plexiform or multinodular architecture.²⁴ Immunohistochemically, tumor cells stain positively for S-100 protein, type IV collagen, and vimentin. The capsule, composed of perineural cells, stains positive for epithelial membrane antigen. A neurofilament stain will highlight axons within the tumor.^24,25 Currently, palisaded encapsulated neuroma does not have a well-established link to known neurocutaneous or inherited syndromes. Excision is curative with a low risk of recurrence.²⁶ 

Sclerotic fibromas (SFs) were first reported by Weary et al²⁷ as multiple tumors involving the tongues of patients with Cowden syndrome. Sporadic or solitary SFs of the skin in patients without Cowden syndrome have been reported, and both multiple and solitary SFs present with similar pathologic changes.^28-30 Clinically, the solitary variant manifests as a well-demarcated, flesh-colored to erythematous, waxy papule or nodule with no site or sex predilection.^30,31 Histologically, SF demonstrates a well-demarcated, nonencapsulated dermal nodule composed of hypocellular and sclerotic collagen bundles with scattered spindled cells and prominent clefts resembling Vincent van Gogh's Starry Night or plywood (Figure 4). Immunohistochemically, the spindled cells strongly express CD34. Factor XIIIa and markers of melanocytic, neural, and muscular differentiation are negative. When rendering a diagnosis in a patient with multiple SFs, a comment regarding the possibility of Cowden syndrome should be mentioned.³² 

The Diagnosis: Sclerosing Perineurioma 

Sclerosing perineurioma, first described in 1997 by Fetsch and Miettinen,¹ is a subtype of perineurioma with a strong predilection for the fingers and palms of young adults. Rare cases involving extra-acral sites including the forearm, elbow, axilla, back, neck, lower leg, thigh, knee, lips, nose, and mouth have been reported.^2-4 Perineurioma is a relatively uncommon and benign peripheral nerve sheath tumor with exclusive perineurial differentiation.⁵ Perineurioma is divided into intraneural and extraneural types; the latter are further subclassified into soft tissue, sclerosing, reticular, and plexiform types. Other rare forms include the sclerosing, Pacinian corpuscle-like perineurioma, lipomatous perineurioma, perineurioma with xanthomatous areas, and perineurioma with granular cells.^6,7  

Clinically, sclerosing perineurioma usually presents as a solitary lesion; however, rare cases of multiple lesions have been reported.⁸ Our patient presented with a solitary papule on the nose. Histopathologically, sclerosing perineurioma demonstrates slender spindle cells in a whorled growth pattern (onion skin) embedded in a hyalinized, lamellar, and dense collagenous stroma with intervening cleftlike spaces. Immunohistochemically, the spindle cells of our case stained positive for epithelial membrane antigen (quiz images). Other positive immunostains for perineurioma include claudin-1 and glucose transporter 1 (GLUT1). Perineurioma lacks expression of S-100 but can express CD34.² As a benign tumor, the prognosis of sclerosing perineurioma is excellent. Complete local excision is considered curative.¹  

Angiofibroma, also known as fibrous papule, is a common and benign lesion located primarily on or in close proximity to the nose.⁹ Angiofibromas can be associated with genodermatoses such as tuberous sclerosis, multiple endocrine neoplasia type 1, or Birt-Hogg-Dubé syndrome. When angiofibromas involve the penis, they are called pearly penile papules. Ungual angiofibroma, also known as Koenen tumor, occurs underneath the nail.^10-12 Both facial angiofibromas (>3) and ungual angiofibromas (>2) are independent major criteria for tuberous sclerosis.¹³ Clinically, angiofibroma presents as a small, dome-shaped, pink papule arising on the lower portion of the nose or nearby area of the central face. Histopathologically, angiofibromas classically demonstrate increased dilated vessels and fibrosis in the dermis. Stellate, plump, spindle-shaped, and multinucleated cells can be seen in the collagenous stroma. The collagen fibers around hair follicles are arranged concentrically, resulting in an onion skin-like appearance. The epidermal rete ridges can be effaced (Figure 1). Increased numbers of single-unit melanocytes along the dermoepidermal junction can be seen in some cases. Immunohistochemically, a variable number of spindled and multinucleated cells in the dermis stain with factor XIIIa. There are at least 7 histologic variants of angiofibroma including hypercellular, pigmented, inflammatory, pleomorphic, clear cell, granular cell, and epithelioid.^9,14 

Palisaded encapsulated neuroma, also referred to as solitary circumscribed neuroma, was first described by Reed et al²¹ in 1972. It is a benign and solitary, firm, dome-shaped, flesh-colored papule that occurs in middle-aged adults, predominately near mucocutaneous junctions of the face. Other locations include the oral mucosa, eyelid, nasal fossa, shoulder, arm, hand, foot, and glans penis.^22,23 Histopathologically, palisaded encapsulated neuroma demonstrates a solitary, well-circumscribed, partially encapsulated, intradermal nodule composed of interweaving fascicles of spindle cells with prominent clefts (Figure 3). Rarely, palisaded encapsulated neuroma may have a plexiform or multinodular architecture.²⁴ Immunohistochemically, tumor cells stain positively for S-100 protein, type IV collagen, and vimentin. The capsule, composed of perineural cells, stains positive for epithelial membrane antigen. A neurofilament stain will highlight axons within the tumor.^24,25 Currently, palisaded encapsulated neuroma does not have a well-established link to known neurocutaneous or inherited syndromes. Excision is curative with a low risk of recurrence.²⁶ 

Sclerotic fibromas (SFs) were first reported by Weary et al²⁷ as multiple tumors involving the tongues of patients with Cowden syndrome. Sporadic or solitary SFs of the skin in patients without Cowden syndrome have been reported, and both multiple and solitary SFs present with similar pathologic changes.^28-30 Clinically, the solitary variant manifests as a well-demarcated, flesh-colored to erythematous, waxy papule or nodule with no site or sex predilection.^30,31 Histologically, SF demonstrates a well-demarcated, nonencapsulated dermal nodule composed of hypocellular and sclerotic collagen bundles with scattered spindled cells and prominent clefts resembling Vincent van Gogh's Starry Night or plywood (Figure 4). Immunohistochemically, the spindled cells strongly express CD34. Factor XIIIa and markers of melanocytic, neural, and muscular differentiation are negative. When rendering a diagnosis in a patient with multiple SFs, a comment regarding the possibility of Cowden syndrome should be mentioned.³² 

The Diagnosis: Sclerosing Perineurioma 

Sclerosing perineurioma, first described in 1997 by Fetsch and Miettinen,¹ is a subtype of perineurioma with a strong predilection for the fingers and palms of young adults. Rare cases involving extra-acral sites including the forearm, elbow, axilla, back, neck, lower leg, thigh, knee, lips, nose, and mouth have been reported.^2-4 Perineurioma is a relatively uncommon and benign peripheral nerve sheath tumor with exclusive perineurial differentiation.⁵ Perineurioma is divided into intraneural and extraneural types; the latter are further subclassified into soft tissue, sclerosing, reticular, and plexiform types. Other rare forms include the sclerosing, Pacinian corpuscle-like perineurioma, lipomatous perineurioma, perineurioma with xanthomatous areas, and perineurioma with granular cells.^6,7  

Clinically, sclerosing perineurioma usually presents as a solitary lesion; however, rare cases of multiple lesions have been reported.⁸ Our patient presented with a solitary papule on the nose. Histopathologically, sclerosing perineurioma demonstrates slender spindle cells in a whorled growth pattern (onion skin) embedded in a hyalinized, lamellar, and dense collagenous stroma with intervening cleftlike spaces. Immunohistochemically, the spindle cells of our case stained positive for epithelial membrane antigen (quiz images). Other positive immunostains for perineurioma include claudin-1 and glucose transporter 1 (GLUT1). Perineurioma lacks expression of S-100 but can express CD34.² As a benign tumor, the prognosis of sclerosing perineurioma is excellent. Complete local excision is considered curative.¹  

Angiofibroma, also known as fibrous papule, is a common and benign lesion located primarily on or in close proximity to the nose.⁹ Angiofibromas can be associated with genodermatoses such as tuberous sclerosis, multiple endocrine neoplasia type 1, or Birt-Hogg-Dubé syndrome. When angiofibromas involve the penis, they are called pearly penile papules. Ungual angiofibroma, also known as Koenen tumor, occurs underneath the nail.^10-12 Both facial angiofibromas (>3) and ungual angiofibromas (>2) are independent major criteria for tuberous sclerosis.¹³ Clinically, angiofibroma presents as a small, dome-shaped, pink papule arising on the lower portion of the nose or nearby area of the central face. Histopathologically, angiofibromas classically demonstrate increased dilated vessels and fibrosis in the dermis. Stellate, plump, spindle-shaped, and multinucleated cells can be seen in the collagenous stroma. The collagen fibers around hair follicles are arranged concentrically, resulting in an onion skin-like appearance. The epidermal rete ridges can be effaced (Figure 1). Increased numbers of single-unit melanocytes along the dermoepidermal junction can be seen in some cases. Immunohistochemically, a variable number of spindled and multinucleated cells in the dermis stain with factor XIIIa. There are at least 7 histologic variants of angiofibroma including hypercellular, pigmented, inflammatory, pleomorphic, clear cell, granular cell, and epithelioid.^9,14 

Palisaded encapsulated neuroma, also referred to as solitary circumscribed neuroma, was first described by Reed et al²¹ in 1972. It is a benign and solitary, firm, dome-shaped, flesh-colored papule that occurs in middle-aged adults, predominately near mucocutaneous junctions of the face. Other locations include the oral mucosa, eyelid, nasal fossa, shoulder, arm, hand, foot, and glans penis.^22,23 Histopathologically, palisaded encapsulated neuroma demonstrates a solitary, well-circumscribed, partially encapsulated, intradermal nodule composed of interweaving fascicles of spindle cells with prominent clefts (Figure 3). Rarely, palisaded encapsulated neuroma may have a plexiform or multinodular architecture.²⁴ Immunohistochemically, tumor cells stain positively for S-100 protein, type IV collagen, and vimentin. The capsule, composed of perineural cells, stains positive for epithelial membrane antigen. A neurofilament stain will highlight axons within the tumor.^24,25 Currently, palisaded encapsulated neuroma does not have a well-established link to known neurocutaneous or inherited syndromes. Excision is curative with a low risk of recurrence.²⁶ 

Sclerotic fibromas (SFs) were first reported by Weary et al²⁷ as multiple tumors involving the tongues of patients with Cowden syndrome. Sporadic or solitary SFs of the skin in patients without Cowden syndrome have been reported, and both multiple and solitary SFs present with similar pathologic changes.^28-30 Clinically, the solitary variant manifests as a well-demarcated, flesh-colored to erythematous, waxy papule or nodule with no site or sex predilection.^30,31 Histologically, SF demonstrates a well-demarcated, nonencapsulated dermal nodule composed of hypocellular and sclerotic collagen bundles with scattered spindled cells and prominent clefts resembling Vincent van Gogh's Starry Night or plywood (Figure 4). Immunohistochemically, the spindled cells strongly express CD34. Factor XIIIa and markers of melanocytic, neural, and muscular differentiation are negative. When rendering a diagnosis in a patient with multiple SFs, a comment regarding the possibility of Cowden syndrome should be mentioned.³² 

Average out-of-pocket costs for Medicare beneficiaries with Alzheimer’s disease were more than 2.7 times higher than for enrollees overall in 2016, according to the Kaiser Family Foundation.

Out-of-pocket spending for Alzheimer’s disease or other dementia was higher than any other chronic condition, averaging $14,913 in 2016 (the latest year for which data are available), compared with $5,460 for all beneficiaries in traditional Medicare, Kaiser investigators said in a recent report based on data for 5,369 respondents to the Medicare Current Beneficiary Survey.

Those totals were divided between services – including long-term care facilities, medical providers and supplies, and prescription drugs – and premiums for Medicare and other types of supplemental insurance. The premium associated with Alzheimer’s, $1,643, was the lowest of any major chronic condition, but the average cost for services, $13,269, was almost twice as high as the next most expensive condition, Parkinson’s disease, and more than four times higher than the overall Medicare average, Juliette Cubanski, PhD, and associates said.

Out-of-pocket costs are higher for patients with Alzheimer’s and Parkinson’s because “these beneficiaries are more likely to reside in a long-term care facility than those with other conditions,” they said. In 2016, out-of-pocket spending on long-term care facility services averaged over $27,000 for Medicare beneficiaries with Alzheimer’s and other dementia and over $28,000 for those with Parkinson’s disease. For all traditional Medicare beneficiaries, average out-of-pocket spending on such services was $1,014.

“The fact that traditional Medicare does not have an annual out-of-pocket limit and does not cover certain services that older adults are more likely to need may undermine the financial security that Medicare provides, especially for people with significant needs and limited incomes. Addressing these gaps would help to alleviate the financial burden of health care for people with Medicare, although doing so would also increase federal spending and taxes,” Dr. Cubanski and associates wrote.

[email protected]

Average out-of-pocket costs for Medicare beneficiaries with Alzheimer’s disease were more than 2.7 times higher than for enrollees overall in 2016, according to the Kaiser Family Foundation.

Out-of-pocket spending for Alzheimer’s disease or other dementia was higher than any other chronic condition, averaging $14,913 in 2016 (the latest year for which data are available), compared with $5,460 for all beneficiaries in traditional Medicare, Kaiser investigators said in a recent report based on data for 5,369 respondents to the Medicare Current Beneficiary Survey.

Those totals were divided between services – including long-term care facilities, medical providers and supplies, and prescription drugs – and premiums for Medicare and other types of supplemental insurance. The premium associated with Alzheimer’s, $1,643, was the lowest of any major chronic condition, but the average cost for services, $13,269, was almost twice as high as the next most expensive condition, Parkinson’s disease, and more than four times higher than the overall Medicare average, Juliette Cubanski, PhD, and associates said.

Out-of-pocket costs are higher for patients with Alzheimer’s and Parkinson’s because “these beneficiaries are more likely to reside in a long-term care facility than those with other conditions,” they said. In 2016, out-of-pocket spending on long-term care facility services averaged over $27,000 for Medicare beneficiaries with Alzheimer’s and other dementia and over $28,000 for those with Parkinson’s disease. For all traditional Medicare beneficiaries, average out-of-pocket spending on such services was $1,014.

“The fact that traditional Medicare does not have an annual out-of-pocket limit and does not cover certain services that older adults are more likely to need may undermine the financial security that Medicare provides, especially for people with significant needs and limited incomes. Addressing these gaps would help to alleviate the financial burden of health care for people with Medicare, although doing so would also increase federal spending and taxes,” Dr. Cubanski and associates wrote.

[email protected]

Average out-of-pocket costs for Medicare beneficiaries with Alzheimer’s disease were more than 2.7 times higher than for enrollees overall in 2016, according to the Kaiser Family Foundation.

Out-of-pocket spending for Alzheimer’s disease or other dementia was higher than any other chronic condition, averaging $14,913 in 2016 (the latest year for which data are available), compared with $5,460 for all beneficiaries in traditional Medicare, Kaiser investigators said in a recent report based on data for 5,369 respondents to the Medicare Current Beneficiary Survey.

Those totals were divided between services – including long-term care facilities, medical providers and supplies, and prescription drugs – and premiums for Medicare and other types of supplemental insurance. The premium associated with Alzheimer’s, $1,643, was the lowest of any major chronic condition, but the average cost for services, $13,269, was almost twice as high as the next most expensive condition, Parkinson’s disease, and more than four times higher than the overall Medicare average, Juliette Cubanski, PhD, and associates said.

Out-of-pocket costs are higher for patients with Alzheimer’s and Parkinson’s because “these beneficiaries are more likely to reside in a long-term care facility than those with other conditions,” they said. In 2016, out-of-pocket spending on long-term care facility services averaged over $27,000 for Medicare beneficiaries with Alzheimer’s and other dementia and over $28,000 for those with Parkinson’s disease. For all traditional Medicare beneficiaries, average out-of-pocket spending on such services was $1,014.

“The fact that traditional Medicare does not have an annual out-of-pocket limit and does not cover certain services that older adults are more likely to need may undermine the financial security that Medicare provides, especially for people with significant needs and limited incomes. Addressing these gaps would help to alleviate the financial burden of health care for people with Medicare, although doing so would also increase federal spending and taxes,” Dr. Cubanski and associates wrote.

[email protected]

LAS VEGAS – New acne treatment options include a tetracycline antibiotic and a recently approved topical formulation of minocycline, according to Linda Stein Gold, MD, who reviewed the data on these two therapies, as well as cannabidiol (CBD) and an androgen receptor antagonist, which are currently in clinical trials, at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

When considering antibiotic therapy for patients with moderate to severe acne, sarecycline, approved for that indication in October 2018, has improved anti-inflammatory properties and a narrower spectrum of activity, compared with other tetracycline-class antibiotics used for the condition, according to Dr. Stein Gold, director of dermatology research at Henry Ford Health System in Detroit. In two identically designed, 12-week randomized trials, SC 1401 and SC1402, researchers evaluated the efficacy and safety of an approximate 1.5–mg/kg per day dose of sarecycline in comparison with placebo in patients with moderate to severe facial acne aged 9-45 years (J Drugs Dermatol. 2018 Sept 1;17[9]:987-96). “We started to see separation in the inflammatory lesions as early as week 3, and a nice separation versus placebo over the course of 12 weeks,” said Dr. Stein Gold, one of the study investigators. “In all, 22% of patients got clear or almost clear with monotherapy. That’s fairly good.”

She noted that there was consistency in the reductions of lesion count achieved in both studies. Improvements were seen through to 12 weeks, with statistically significant reduction seen as early as 3 weeks in both studies. Sarecycline was also statistically superior to placebo at every time point studied in both trials.

In order to be judged a successful outcome, the subject had to have a 12-week Investigator’s Global Assessment (IGA) score with a 2-point or greater decrease (improvement) from baseline score on the IGA in each location, for patients who have a baseline IGA of 2 or greater, and to be clear (0) or almost clear (1). The same IGA scale was used for the chest and back assessments as was used for facial acne; the researchers observed statistically significant improvements in IGA score for both chest and back acne across both studies at week 12.

Sarecycline also had a favorable safety profile, with no treatment-emergent vertigo or tinnitus adverse events, she noted. Treatment-emergent vestibular and phototoxic adverse events both occurred in fewer than 1% of sarecycline patients. Among females, rates of yeast infections were low. When she recommends a course of this drug for her patients, “I never overpromise,” she said. “I tell my acne patients, ‘We measure your success in weeks and months, not days.’ I always tell them, ‘Take a selfie today and take a selfie every few weeks. When you come back in, we’ll review your progress and see how things went.’ ”

Researchers have also been studying topical minocycline as a treatment option. Minocycline is a large molecule that Dr. Stein Gold characterized as being “very challenging” to deliver topically. “It’s also challenging to keep it stable in a topical formulation.” However, results from two identical phase 3 trials found 4% topical minocycline foam significantly reduced both inflammatory and noninflammatory lesions and improved IGA scores in patients with moderate to severe acne when treated daily for 12 weeks (J Am Acad Dermatol. 2019 Jan;80[1]:168-77).

“This drug has an interesting vehicle,” said Dr. Stein Gold, who was one of the study investigators. “If you take the vehicle itself and you put it next to sebum, it causes sebum to melt at lower temperatures. Why does this matter? If you’re dissolving sebum, maybe you’re creating an easier pathway for the drug to get delivered into the skin and into the hair follicles. We don’t know all the details.” In the two trials, 15%-31% of patients achieved clearance or near clearance of all lesions. “How did it do in terms of decreasing papules and pustules? It did pretty well,” she said. “We want drugs to meet their match in everything that we do.” In terms of tolerability, skin-related adverse events were reported in fewer than 1% of subjects treated with 4% topical minocycline foam. She noted that by delivering minocycline topically, “we get huge concentrations in the skin, but almost negligible amounts in the systemic circulation, which is important. We want to keep [the drug] in the skin; we don’t want it in our system.”

(The Food and Drug Administration approved minocycline foam 4% in October 2019 for treating inflammatory lesions associated with non-nodular moderate to severe acne).

Another potential treatment on the horizon is cortexolone 17a-propionate, a novel androgen receptor antagonist that inhibits production of lipids and inflammatory cytokines from sebocytes in vitro. “When used around the sebaceous gland, we find that the amount of sebum produced goes down,” she said, noting that phase 3 trials of the agent have been completed.

“We also find that abnormal keratinization subsequently goes down. Just putting this on the skin significantly reduced acne as monotherapy in patients with moderate to severe acne. We were able to get them to clear or almost clear. It worked on comedones, papules, and pustules. Hopefully, it will get FDA approval. This fills the one unmet need we haven’t had topically in terms of decreasing sebum production.”

Clinical trials of CBD are also under way for acne and atopic dermatitis. “It could work for acne because there are some studies showing that might work on sebaceous glands to decrease sebum production,” she said. “CBD has been shown to have positive effects on abnormal keratinization, and it has been shown to have anti-inflammatory effects. Maybe we’ll have another mechanism of action for acne.”

Dr. Gold disclosed that she is on the speakers bureau for Almirall, Galderma, Leo Pharma, Ortho Dermatologics, Pfizer, and Sanofi/Regeneron. She is a consultant for Dermavant, Foamix, Galderma, Leo Pharma, Pfizer, Novartis, Ortho Dermatologics, and holds stock/stock options in AbbVie, Dermavant, Eli Lilly, Foamix, Galderma, Incyte, Leo Pharma, Novartis, Ortho Dermatologics, Pfizer, and Sol-Gel.

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

[email protected]

LAS VEGAS – New acne treatment options include a tetracycline antibiotic and a recently approved topical formulation of minocycline, according to Linda Stein Gold, MD, who reviewed the data on these two therapies, as well as cannabidiol (CBD) and an androgen receptor antagonist, which are currently in clinical trials, at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

When considering antibiotic therapy for patients with moderate to severe acne, sarecycline, approved for that indication in October 2018, has improved anti-inflammatory properties and a narrower spectrum of activity, compared with other tetracycline-class antibiotics used for the condition, according to Dr. Stein Gold, director of dermatology research at Henry Ford Health System in Detroit. In two identically designed, 12-week randomized trials, SC 1401 and SC1402, researchers evaluated the efficacy and safety of an approximate 1.5–mg/kg per day dose of sarecycline in comparison with placebo in patients with moderate to severe facial acne aged 9-45 years (J Drugs Dermatol. 2018 Sept 1;17[9]:987-96). “We started to see separation in the inflammatory lesions as early as week 3, and a nice separation versus placebo over the course of 12 weeks,” said Dr. Stein Gold, one of the study investigators. “In all, 22% of patients got clear or almost clear with monotherapy. That’s fairly good.”

She noted that there was consistency in the reductions of lesion count achieved in both studies. Improvements were seen through to 12 weeks, with statistically significant reduction seen as early as 3 weeks in both studies. Sarecycline was also statistically superior to placebo at every time point studied in both trials.

In order to be judged a successful outcome, the subject had to have a 12-week Investigator’s Global Assessment (IGA) score with a 2-point or greater decrease (improvement) from baseline score on the IGA in each location, for patients who have a baseline IGA of 2 or greater, and to be clear (0) or almost clear (1). The same IGA scale was used for the chest and back assessments as was used for facial acne; the researchers observed statistically significant improvements in IGA score for both chest and back acne across both studies at week 12.

Sarecycline also had a favorable safety profile, with no treatment-emergent vertigo or tinnitus adverse events, she noted. Treatment-emergent vestibular and phototoxic adverse events both occurred in fewer than 1% of sarecycline patients. Among females, rates of yeast infections were low. When she recommends a course of this drug for her patients, “I never overpromise,” she said. “I tell my acne patients, ‘We measure your success in weeks and months, not days.’ I always tell them, ‘Take a selfie today and take a selfie every few weeks. When you come back in, we’ll review your progress and see how things went.’ ”

Researchers have also been studying topical minocycline as a treatment option. Minocycline is a large molecule that Dr. Stein Gold characterized as being “very challenging” to deliver topically. “It’s also challenging to keep it stable in a topical formulation.” However, results from two identical phase 3 trials found 4% topical minocycline foam significantly reduced both inflammatory and noninflammatory lesions and improved IGA scores in patients with moderate to severe acne when treated daily for 12 weeks (J Am Acad Dermatol. 2019 Jan;80[1]:168-77).

“This drug has an interesting vehicle,” said Dr. Stein Gold, who was one of the study investigators. “If you take the vehicle itself and you put it next to sebum, it causes sebum to melt at lower temperatures. Why does this matter? If you’re dissolving sebum, maybe you’re creating an easier pathway for the drug to get delivered into the skin and into the hair follicles. We don’t know all the details.” In the two trials, 15%-31% of patients achieved clearance or near clearance of all lesions. “How did it do in terms of decreasing papules and pustules? It did pretty well,” she said. “We want drugs to meet their match in everything that we do.” In terms of tolerability, skin-related adverse events were reported in fewer than 1% of subjects treated with 4% topical minocycline foam. She noted that by delivering minocycline topically, “we get huge concentrations in the skin, but almost negligible amounts in the systemic circulation, which is important. We want to keep [the drug] in the skin; we don’t want it in our system.”

(The Food and Drug Administration approved minocycline foam 4% in October 2019 for treating inflammatory lesions associated with non-nodular moderate to severe acne).

Another potential treatment on the horizon is cortexolone 17a-propionate, a novel androgen receptor antagonist that inhibits production of lipids and inflammatory cytokines from sebocytes in vitro. “When used around the sebaceous gland, we find that the amount of sebum produced goes down,” she said, noting that phase 3 trials of the agent have been completed.

“We also find that abnormal keratinization subsequently goes down. Just putting this on the skin significantly reduced acne as monotherapy in patients with moderate to severe acne. We were able to get them to clear or almost clear. It worked on comedones, papules, and pustules. Hopefully, it will get FDA approval. This fills the one unmet need we haven’t had topically in terms of decreasing sebum production.”

Clinical trials of CBD are also under way for acne and atopic dermatitis. “It could work for acne because there are some studies showing that might work on sebaceous glands to decrease sebum production,” she said. “CBD has been shown to have positive effects on abnormal keratinization, and it has been shown to have anti-inflammatory effects. Maybe we’ll have another mechanism of action for acne.”

Dr. Gold disclosed that she is on the speakers bureau for Almirall, Galderma, Leo Pharma, Ortho Dermatologics, Pfizer, and Sanofi/Regeneron. She is a consultant for Dermavant, Foamix, Galderma, Leo Pharma, Pfizer, Novartis, Ortho Dermatologics, and holds stock/stock options in AbbVie, Dermavant, Eli Lilly, Foamix, Galderma, Incyte, Leo Pharma, Novartis, Ortho Dermatologics, Pfizer, and Sol-Gel.

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

[email protected]

LAS VEGAS – New acne treatment options include a tetracycline antibiotic and a recently approved topical formulation of minocycline, according to Linda Stein Gold, MD, who reviewed the data on these two therapies, as well as cannabidiol (CBD) and an androgen receptor antagonist, which are currently in clinical trials, at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

When considering antibiotic therapy for patients with moderate to severe acne, sarecycline, approved for that indication in October 2018, has improved anti-inflammatory properties and a narrower spectrum of activity, compared with other tetracycline-class antibiotics used for the condition, according to Dr. Stein Gold, director of dermatology research at Henry Ford Health System in Detroit. In two identically designed, 12-week randomized trials, SC 1401 and SC1402, researchers evaluated the efficacy and safety of an approximate 1.5–mg/kg per day dose of sarecycline in comparison with placebo in patients with moderate to severe facial acne aged 9-45 years (J Drugs Dermatol. 2018 Sept 1;17[9]:987-96). “We started to see separation in the inflammatory lesions as early as week 3, and a nice separation versus placebo over the course of 12 weeks,” said Dr. Stein Gold, one of the study investigators. “In all, 22% of patients got clear or almost clear with monotherapy. That’s fairly good.”

She noted that there was consistency in the reductions of lesion count achieved in both studies. Improvements were seen through to 12 weeks, with statistically significant reduction seen as early as 3 weeks in both studies. Sarecycline was also statistically superior to placebo at every time point studied in both trials.

In order to be judged a successful outcome, the subject had to have a 12-week Investigator’s Global Assessment (IGA) score with a 2-point or greater decrease (improvement) from baseline score on the IGA in each location, for patients who have a baseline IGA of 2 or greater, and to be clear (0) or almost clear (1). The same IGA scale was used for the chest and back assessments as was used for facial acne; the researchers observed statistically significant improvements in IGA score for both chest and back acne across both studies at week 12.

Sarecycline also had a favorable safety profile, with no treatment-emergent vertigo or tinnitus adverse events, she noted. Treatment-emergent vestibular and phototoxic adverse events both occurred in fewer than 1% of sarecycline patients. Among females, rates of yeast infections were low. When she recommends a course of this drug for her patients, “I never overpromise,” she said. “I tell my acne patients, ‘We measure your success in weeks and months, not days.’ I always tell them, ‘Take a selfie today and take a selfie every few weeks. When you come back in, we’ll review your progress and see how things went.’ ”

Researchers have also been studying topical minocycline as a treatment option. Minocycline is a large molecule that Dr. Stein Gold characterized as being “very challenging” to deliver topically. “It’s also challenging to keep it stable in a topical formulation.” However, results from two identical phase 3 trials found 4% topical minocycline foam significantly reduced both inflammatory and noninflammatory lesions and improved IGA scores in patients with moderate to severe acne when treated daily for 12 weeks (J Am Acad Dermatol. 2019 Jan;80[1]:168-77).

“This drug has an interesting vehicle,” said Dr. Stein Gold, who was one of the study investigators. “If you take the vehicle itself and you put it next to sebum, it causes sebum to melt at lower temperatures. Why does this matter? If you’re dissolving sebum, maybe you’re creating an easier pathway for the drug to get delivered into the skin and into the hair follicles. We don’t know all the details.” In the two trials, 15%-31% of patients achieved clearance or near clearance of all lesions. “How did it do in terms of decreasing papules and pustules? It did pretty well,” she said. “We want drugs to meet their match in everything that we do.” In terms of tolerability, skin-related adverse events were reported in fewer than 1% of subjects treated with 4% topical minocycline foam. She noted that by delivering minocycline topically, “we get huge concentrations in the skin, but almost negligible amounts in the systemic circulation, which is important. We want to keep [the drug] in the skin; we don’t want it in our system.”

(The Food and Drug Administration approved minocycline foam 4% in October 2019 for treating inflammatory lesions associated with non-nodular moderate to severe acne).

Another potential treatment on the horizon is cortexolone 17a-propionate, a novel androgen receptor antagonist that inhibits production of lipids and inflammatory cytokines from sebocytes in vitro. “When used around the sebaceous gland, we find that the amount of sebum produced goes down,” she said, noting that phase 3 trials of the agent have been completed.

“We also find that abnormal keratinization subsequently goes down. Just putting this on the skin significantly reduced acne as monotherapy in patients with moderate to severe acne. We were able to get them to clear or almost clear. It worked on comedones, papules, and pustules. Hopefully, it will get FDA approval. This fills the one unmet need we haven’t had topically in terms of decreasing sebum production.”

Clinical trials of CBD are also under way for acne and atopic dermatitis. “It could work for acne because there are some studies showing that might work on sebaceous glands to decrease sebum production,” she said. “CBD has been shown to have positive effects on abnormal keratinization, and it has been shown to have anti-inflammatory effects. Maybe we’ll have another mechanism of action for acne.”

Dr. Gold disclosed that she is on the speakers bureau for Almirall, Galderma, Leo Pharma, Ortho Dermatologics, Pfizer, and Sanofi/Regeneron. She is a consultant for Dermavant, Foamix, Galderma, Leo Pharma, Pfizer, Novartis, Ortho Dermatologics, and holds stock/stock options in AbbVie, Dermavant, Eli Lilly, Foamix, Galderma, Incyte, Leo Pharma, Novartis, Ortho Dermatologics, Pfizer, and Sol-Gel.

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

[email protected]

Taking daily aspirin may help keep nonalcoholic fatty liver disease (NAFLD) from progressing to liver fibrosis and nonalcoholic steatohepatitis (NASH), suggest the results of a prospective study of 361 adults.

Previously, preclinical evidence had linked aspirin to fibrogenesis prevention in fatty liver disease, but this is the first report of a prospective study to do so. Daily aspirin use “was associated with less severe histologic features of NAFLD (nonalcoholic fatty liver disease) at study enrollment and with significantly lower risk for advanced fibrosis over time in a duration-dependent manner,” wrote Tracey G. Simon, MD, MPH, and her associates. Their report is in Clinical Gastroenterology and Hepatology.

The study comprised 361 adults with biopsy-confirmed NAFLD who were enrolled in the Massachusetts General Hospital NAFLD Repository between 2006 and 2015. At baseline, 151 individuals were already on daily aspirin, usually to reduce the primary (54%) or secondary (30%) risk of cardiovascular disease. Median duration of aspirin use was 2.5 years. After a median 7.4 years of follow-up (which was similar between aspirin users and nonusers), daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% confidence interval, 0.37-0.89) and fibrosis (aOR, 0.54; 95% CI, 0.31-0.82).

The researchers did not find a similar protective effect for nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin (adjusted hazard ratio for advanced fibrosis, 0.93; 95% CI, 0.81–1.05). This might be because of differences between how aspirin and nonaspirin NSAIDs affect COX isoforms – aspirin does so irreversibly, while other NSAIDs have a reversible effect, they added. “Nonaspirin NSAIDs also disrupt the intestinal barrier, increasing delivery of proinflammatory cytokines to the liver,” they wrote. “Finally, aspirin uniquely modulates bioactive lipids by stimulating the biosynthesis of pro-resolving mediators and inhibiting proinflammatory lipids, which in turn may prevent progressive liver damage.”

In this study, a single blinded hepatopathologist interpreted baseline liver biopsy specimens, and patients were followed every 3-6 months with clinical examinations and serial calculations of FIB-4, NFS, and APRI scores. All patients were followed for at least a year. Patients were classified as users of nonaspirin NSAIDs if they reported using an NSAID besides aspirin at least twice weekly, or if they had been prescribed drugs such as ibuprofen, naproxen, ketoprofen, diclofenac, or indomethacin.

In a longitudinal analysis of the 317 patients who had early-stage (F0-2) fibrosis at baseline, 86 developed new-onset advanced fibrosis over a median of 3,692 person-years, the researchers said. In all, 26 individuals developed hepatic decompensation and 18 patients died, including eight from liver-related causes. Importantly, the link between aspirin and decreased risk of fibrosis progression seemed to depend on duration of use (adjusted P trend = .026), with the greatest benefit seen with 4 years or more of use (aHR, 0.50; 95% CI, 0.35-0.73). Although subgroup analyses were limited by lack of power, daily aspirin use was associated with a 36% lower odds of incident advanced fibrosis among the 72 study participants who had paired biopsy samples, even after accounting for the effect of age, sex, baseline fibrosis stage, and time between biopsies (aOR, 0.64; 95% CI, 0.50-0.80).

“Our findings add to the growing literature supporting the potential hepatoprotective effects of aspirin in NAFLD,” the researchers concluded. “Research to uncover the mechanisms by which aspirin might prevent fibrogenesis could help develop urgently needed antifibrotic therapies for NAFLD.”

Funders included the National Institutes of Health and the AASLD Foundation. The investigators reported having no conflicts of interest.

SOURCE: Simon TG et al. Clin Gastroenterol Hepatol. 2019 May 8.

Taking daily aspirin may help keep nonalcoholic fatty liver disease (NAFLD) from progressing to liver fibrosis and nonalcoholic steatohepatitis (NASH), suggest the results of a prospective study of 361 adults.

Previously, preclinical evidence had linked aspirin to fibrogenesis prevention in fatty liver disease, but this is the first report of a prospective study to do so. Daily aspirin use “was associated with less severe histologic features of NAFLD (nonalcoholic fatty liver disease) at study enrollment and with significantly lower risk for advanced fibrosis over time in a duration-dependent manner,” wrote Tracey G. Simon, MD, MPH, and her associates. Their report is in Clinical Gastroenterology and Hepatology.

The study comprised 361 adults with biopsy-confirmed NAFLD who were enrolled in the Massachusetts General Hospital NAFLD Repository between 2006 and 2015. At baseline, 151 individuals were already on daily aspirin, usually to reduce the primary (54%) or secondary (30%) risk of cardiovascular disease. Median duration of aspirin use was 2.5 years. After a median 7.4 years of follow-up (which was similar between aspirin users and nonusers), daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% confidence interval, 0.37-0.89) and fibrosis (aOR, 0.54; 95% CI, 0.31-0.82).

The researchers did not find a similar protective effect for nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin (adjusted hazard ratio for advanced fibrosis, 0.93; 95% CI, 0.81–1.05). This might be because of differences between how aspirin and nonaspirin NSAIDs affect COX isoforms – aspirin does so irreversibly, while other NSAIDs have a reversible effect, they added. “Nonaspirin NSAIDs also disrupt the intestinal barrier, increasing delivery of proinflammatory cytokines to the liver,” they wrote. “Finally, aspirin uniquely modulates bioactive lipids by stimulating the biosynthesis of pro-resolving mediators and inhibiting proinflammatory lipids, which in turn may prevent progressive liver damage.”

In this study, a single blinded hepatopathologist interpreted baseline liver biopsy specimens, and patients were followed every 3-6 months with clinical examinations and serial calculations of FIB-4, NFS, and APRI scores. All patients were followed for at least a year. Patients were classified as users of nonaspirin NSAIDs if they reported using an NSAID besides aspirin at least twice weekly, or if they had been prescribed drugs such as ibuprofen, naproxen, ketoprofen, diclofenac, or indomethacin.

In a longitudinal analysis of the 317 patients who had early-stage (F0-2) fibrosis at baseline, 86 developed new-onset advanced fibrosis over a median of 3,692 person-years, the researchers said. In all, 26 individuals developed hepatic decompensation and 18 patients died, including eight from liver-related causes. Importantly, the link between aspirin and decreased risk of fibrosis progression seemed to depend on duration of use (adjusted P trend = .026), with the greatest benefit seen with 4 years or more of use (aHR, 0.50; 95% CI, 0.35-0.73). Although subgroup analyses were limited by lack of power, daily aspirin use was associated with a 36% lower odds of incident advanced fibrosis among the 72 study participants who had paired biopsy samples, even after accounting for the effect of age, sex, baseline fibrosis stage, and time between biopsies (aOR, 0.64; 95% CI, 0.50-0.80).

“Our findings add to the growing literature supporting the potential hepatoprotective effects of aspirin in NAFLD,” the researchers concluded. “Research to uncover the mechanisms by which aspirin might prevent fibrogenesis could help develop urgently needed antifibrotic therapies for NAFLD.”

Funders included the National Institutes of Health and the AASLD Foundation. The investigators reported having no conflicts of interest.

SOURCE: Simon TG et al. Clin Gastroenterol Hepatol. 2019 May 8.

Taking daily aspirin may help keep nonalcoholic fatty liver disease (NAFLD) from progressing to liver fibrosis and nonalcoholic steatohepatitis (NASH), suggest the results of a prospective study of 361 adults.

Previously, preclinical evidence had linked aspirin to fibrogenesis prevention in fatty liver disease, but this is the first report of a prospective study to do so. Daily aspirin use “was associated with less severe histologic features of NAFLD (nonalcoholic fatty liver disease) at study enrollment and with significantly lower risk for advanced fibrosis over time in a duration-dependent manner,” wrote Tracey G. Simon, MD, MPH, and her associates. Their report is in Clinical Gastroenterology and Hepatology.

The study comprised 361 adults with biopsy-confirmed NAFLD who were enrolled in the Massachusetts General Hospital NAFLD Repository between 2006 and 2015. At baseline, 151 individuals were already on daily aspirin, usually to reduce the primary (54%) or secondary (30%) risk of cardiovascular disease. Median duration of aspirin use was 2.5 years. After a median 7.4 years of follow-up (which was similar between aspirin users and nonusers), daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% confidence interval, 0.37-0.89) and fibrosis (aOR, 0.54; 95% CI, 0.31-0.82).

The researchers did not find a similar protective effect for nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin (adjusted hazard ratio for advanced fibrosis, 0.93; 95% CI, 0.81–1.05). This might be because of differences between how aspirin and nonaspirin NSAIDs affect COX isoforms – aspirin does so irreversibly, while other NSAIDs have a reversible effect, they added. “Nonaspirin NSAIDs also disrupt the intestinal barrier, increasing delivery of proinflammatory cytokines to the liver,” they wrote. “Finally, aspirin uniquely modulates bioactive lipids by stimulating the biosynthesis of pro-resolving mediators and inhibiting proinflammatory lipids, which in turn may prevent progressive liver damage.”

In this study, a single blinded hepatopathologist interpreted baseline liver biopsy specimens, and patients were followed every 3-6 months with clinical examinations and serial calculations of FIB-4, NFS, and APRI scores. All patients were followed for at least a year. Patients were classified as users of nonaspirin NSAIDs if they reported using an NSAID besides aspirin at least twice weekly, or if they had been prescribed drugs such as ibuprofen, naproxen, ketoprofen, diclofenac, or indomethacin.

In a longitudinal analysis of the 317 patients who had early-stage (F0-2) fibrosis at baseline, 86 developed new-onset advanced fibrosis over a median of 3,692 person-years, the researchers said. In all, 26 individuals developed hepatic decompensation and 18 patients died, including eight from liver-related causes. Importantly, the link between aspirin and decreased risk of fibrosis progression seemed to depend on duration of use (adjusted P trend = .026), with the greatest benefit seen with 4 years or more of use (aHR, 0.50; 95% CI, 0.35-0.73). Although subgroup analyses were limited by lack of power, daily aspirin use was associated with a 36% lower odds of incident advanced fibrosis among the 72 study participants who had paired biopsy samples, even after accounting for the effect of age, sex, baseline fibrosis stage, and time between biopsies (aOR, 0.64; 95% CI, 0.50-0.80).

“Our findings add to the growing literature supporting the potential hepatoprotective effects of aspirin in NAFLD,” the researchers concluded. “Research to uncover the mechanisms by which aspirin might prevent fibrogenesis could help develop urgently needed antifibrotic therapies for NAFLD.”

Funders included the National Institutes of Health and the AASLD Foundation. The investigators reported having no conflicts of interest.

SOURCE: Simon TG et al. Clin Gastroenterol Hepatol. 2019 May 8.

Strong feelings – such as intense anxiety, irritability, or depressed mood – may affect every child for brief periods of time during their development. Parents and pediatricians are wise to not treat them as psychiatric disorders unless they persist for weeks, impair functioning, or are dramatically severe. Psychosis – marked by hallucinations, perceptual distortions, or profoundly disorganized thinking and behavior – typically looks dramatically severe. Even when psychotic symptoms are mild or brief, they can cause very serious distress for parents and clinicians. The worry is that they may represent a “first break,” a psychotic episode that requires much work for recovery, or the beginning of a lifelong struggle with schizophrenia or other chronic psychotic illness.

KatarzynaBialasiewicz/iStock/Getty Images Plus

While it is important to recognize schizophrenia early – because early interventions are thought to improve the course of the disease – schizophrenia in childhood is rare. It is not commonly recognized that psychotic or psychoticlike symptoms are much more common than schizophrenia. In childhood, psychosis is three times more common than in adults, and can indicate a number of different psychiatric or medical problems. While it is important to begin a thoughtful evaluation when a child or teenager presents with psychosis, it also is important to know that the majority of young people who experience psychotic symptoms do not have schizophrenia or other psychotic illness.

Psychosis describes symptoms in which there has been some “break with reality,” often in the form of hallucinations (seeing or hearing things which are not objectively present) or of distorted perceptions (such as paranoia or grandiosity). “Subsyndromal psychotic symptoms” occur when a person experiences these perceptual disturbances but has doubt about whether or not they are real. In frank psychosis, patients have a “fixed and firm” belief in the truth or accuracy of their perceptions, no matter the evidence against them. The voices they hear or hallucinations they see are “real” and there is a wholehearted belief that what the voice says or what they are seeing is as true as what you or I see and hear.

Schizophrenia is a diagnosis that requires the presence of both these “positive” psychotic symptoms and “negative” symptoms of flat affect; loss of motivation, social, or motor abilities; and cognitive impairment. These symptoms typically emerge in late adolescence (median age, 18 years) in males and early adulthood (median age, 25 years) in females, with another (smaller) peak in incidence in middle age. Importantly, the negative symptoms often emerge first so there often is a history of subtle cognitive decline and social withdrawal, one of the most common patterns in children, before psychosis emerges. Schizophrenia is quite rare, with a prevalence of slightly under 1% of the global population, an annual incidence of approximately 15 people per 100,000, and 1 in 40,000 in children under 13 years old, according to the National Institute of Mental Health. Psychotic symptoms are much more common than schizophrenia, affecting approximately 5% of the adult population at any point in time. They are even more common in children and adolescents. A meta-analysis of population-based studies of psychotic symptoms in youth demonstrated a median prevalence of 17% in children aged 9-12 years and 7.5% in adolescents aged 13-18 years.¹ Of course, as with all statistics, much depends on the definitions used to identify this high prevalence rate.

Children and adolescents who report psychotic symptoms are at increased risk for developing schizophrenia, compared with the general population, but most youth with psychotic symptoms will not go on to develop schizophrenia. They are more likely to indicate other, nonpsychotic psychiatric illnesses, such as anxiety or mood disorders, including depression, obsessive compulsive disorder (OCD), and PTSD. In younger children, these symptoms may prove to be benign, but in adolescents they usually indicate the presence of a psychiatric illness. In one study, 57% of children aged 11-13 years with psychotic symptoms were found to have a nonpsychotic psychiatric illness, but the rate jumped to 80% for those aged 13-15 years with psychotic symptoms.² So while psychosis in teenagers only rarely indicates schizophrenia, these symptoms usually indicate the presence of a psychiatric illness, and a psychiatric evaluation should be initiated.

If a child in your practice presents with psychotic symptoms, it is appropriate to assess their safety and then start a medical work-up. Find out from your patient or their parents if their behavior has been affected by their perceptual disturbances. Are they frightened and avoiding school? Are they withdrawing from social relationships? Is their sleep disrupted? Have they been more impulsive or unpredictable? If their behavior has been affected, you should refer to a child psychiatrist to perform a full diagnostic evaluation and help with management of these symptoms.

Your medical work-up should include a drug screen, blood count, metabolic panel, and thyroid function test. Medications, particularly stimulants, steroids, and anticholinergics can cause psychotic symptoms in high doses or vulnerable patients (such as those with a developmental disorder or traumatic brain injury). If the physical or neurologic exam are suggestive, further investigation of the many potential medical sources of psychotic symptoms in youth can be pursued to rule out autoimmune illnesses, endocrine disorders, metabolic illnesses, heavy metal poisoning, neurologic diseases, infectious diseases, and nutritional deficits. It is worth noting that childhood sleep disorders also can present with psychosis. Persistent psychotic symptoms in children are very hard to evaluate and may be the harbinger of a serious psychiatric disorder, so even if the medical work-up is negative and the persistent symptoms are mild and not causing a safety concern, a referral to a child psychiatrist for a full mental health evaluation is appropriate.

Psychotic symptoms in an adolescent sometimes are easier to assess, more worrisome for serious mental illness, and are a high-risk category for self-destructive behavior and substance use. Before you begin a medical work-up, you always should assess for safety, including suicide risk, if your adolescent patient presents with psychotic symptoms. Screening for symptoms of mood, anxiety, and substance use disorders also can help reveal the nature of their presenting problem. If your adolescent patient is using drugs, that does not rule out the possibility of an underlying mood, anxiety, or thought disorder. While intoxication with many drugs may precipitate psychotic symptoms (including stimulants, hallucinogens, and marijuana), others may precipitate psychosis in withdrawal states (alcohol, benzodiazepines, and other CNS depressants). It also is important to note that adolescents with emerging schizophrenia have very high rates of comorbid substance abuse (as high as 60%), so their drug use may not be the cause of their psychotic symptoms. There also is emerging evidence that use of certain drugs during sensitive developmental periods can significantly increase the likelihood of developing schizophrenia in vulnerable populations, such as with regular marijuana use in adolescents who have a family history of schizophrenia.

For those rare pediatric patients who present with both negative and positive symptoms of emerging schizophrenia, early diagnosis and treatment has shown promise in improving the course of the disease. Cognitive-behavioral therapy (CBT) for psychosis has shown promise in lowering the rates of conversion to schizophrenia in select patient populations. This therapy teaches strategies for improving reality testing, cognitive flexibility, and social skills. The social skills appear to be especially important for improving adaptive function, even in those patients who progress to schizophrenia. Family therapies, focused on improving family cohesion, communication, and adaptive functioning, appear to improve family well-being and the course of the patient’s illness (such as fewer and less severe psychotic episodes and improved mood and adaptive function). Early use of antipsychotic medications also appears to improve the course of the illness.

While schizophrenia is not curable, early detection (perhaps by a pediatrician), referral, and treatment can be powerfully protective for patients and their families.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Psychol Med. 2012 Sep;42(9):1857-63.

2. Br J Psychiatry. 2012 Jul;201(1):26-32.

Strong feelings – such as intense anxiety, irritability, or depressed mood – may affect every child for brief periods of time during their development. Parents and pediatricians are wise to not treat them as psychiatric disorders unless they persist for weeks, impair functioning, or are dramatically severe. Psychosis – marked by hallucinations, perceptual distortions, or profoundly disorganized thinking and behavior – typically looks dramatically severe. Even when psychotic symptoms are mild or brief, they can cause very serious distress for parents and clinicians. The worry is that they may represent a “first break,” a psychotic episode that requires much work for recovery, or the beginning of a lifelong struggle with schizophrenia or other chronic psychotic illness.

KatarzynaBialasiewicz/iStock/Getty Images Plus

While it is important to recognize schizophrenia early – because early interventions are thought to improve the course of the disease – schizophrenia in childhood is rare. It is not commonly recognized that psychotic or psychoticlike symptoms are much more common than schizophrenia. In childhood, psychosis is three times more common than in adults, and can indicate a number of different psychiatric or medical problems. While it is important to begin a thoughtful evaluation when a child or teenager presents with psychosis, it also is important to know that the majority of young people who experience psychotic symptoms do not have schizophrenia or other psychotic illness.

Psychosis describes symptoms in which there has been some “break with reality,” often in the form of hallucinations (seeing or hearing things which are not objectively present) or of distorted perceptions (such as paranoia or grandiosity). “Subsyndromal psychotic symptoms” occur when a person experiences these perceptual disturbances but has doubt about whether or not they are real. In frank psychosis, patients have a “fixed and firm” belief in the truth or accuracy of their perceptions, no matter the evidence against them. The voices they hear or hallucinations they see are “real” and there is a wholehearted belief that what the voice says or what they are seeing is as true as what you or I see and hear.

Schizophrenia is a diagnosis that requires the presence of both these “positive” psychotic symptoms and “negative” symptoms of flat affect; loss of motivation, social, or motor abilities; and cognitive impairment. These symptoms typically emerge in late adolescence (median age, 18 years) in males and early adulthood (median age, 25 years) in females, with another (smaller) peak in incidence in middle age. Importantly, the negative symptoms often emerge first so there often is a history of subtle cognitive decline and social withdrawal, one of the most common patterns in children, before psychosis emerges. Schizophrenia is quite rare, with a prevalence of slightly under 1% of the global population, an annual incidence of approximately 15 people per 100,000, and 1 in 40,000 in children under 13 years old, according to the National Institute of Mental Health. Psychotic symptoms are much more common than schizophrenia, affecting approximately 5% of the adult population at any point in time. They are even more common in children and adolescents. A meta-analysis of population-based studies of psychotic symptoms in youth demonstrated a median prevalence of 17% in children aged 9-12 years and 7.5% in adolescents aged 13-18 years.¹ Of course, as with all statistics, much depends on the definitions used to identify this high prevalence rate.

Children and adolescents who report psychotic symptoms are at increased risk for developing schizophrenia, compared with the general population, but most youth with psychotic symptoms will not go on to develop schizophrenia. They are more likely to indicate other, nonpsychotic psychiatric illnesses, such as anxiety or mood disorders, including depression, obsessive compulsive disorder (OCD), and PTSD. In younger children, these symptoms may prove to be benign, but in adolescents they usually indicate the presence of a psychiatric illness. In one study, 57% of children aged 11-13 years with psychotic symptoms were found to have a nonpsychotic psychiatric illness, but the rate jumped to 80% for those aged 13-15 years with psychotic symptoms.² So while psychosis in teenagers only rarely indicates schizophrenia, these symptoms usually indicate the presence of a psychiatric illness, and a psychiatric evaluation should be initiated.

If a child in your practice presents with psychotic symptoms, it is appropriate to assess their safety and then start a medical work-up. Find out from your patient or their parents if their behavior has been affected by their perceptual disturbances. Are they frightened and avoiding school? Are they withdrawing from social relationships? Is their sleep disrupted? Have they been more impulsive or unpredictable? If their behavior has been affected, you should refer to a child psychiatrist to perform a full diagnostic evaluation and help with management of these symptoms.

Your medical work-up should include a drug screen, blood count, metabolic panel, and thyroid function test. Medications, particularly stimulants, steroids, and anticholinergics can cause psychotic symptoms in high doses or vulnerable patients (such as those with a developmental disorder or traumatic brain injury). If the physical or neurologic exam are suggestive, further investigation of the many potential medical sources of psychotic symptoms in youth can be pursued to rule out autoimmune illnesses, endocrine disorders, metabolic illnesses, heavy metal poisoning, neurologic diseases, infectious diseases, and nutritional deficits. It is worth noting that childhood sleep disorders also can present with psychosis. Persistent psychotic symptoms in children are very hard to evaluate and may be the harbinger of a serious psychiatric disorder, so even if the medical work-up is negative and the persistent symptoms are mild and not causing a safety concern, a referral to a child psychiatrist for a full mental health evaluation is appropriate.

Psychotic symptoms in an adolescent sometimes are easier to assess, more worrisome for serious mental illness, and are a high-risk category for self-destructive behavior and substance use. Before you begin a medical work-up, you always should assess for safety, including suicide risk, if your adolescent patient presents with psychotic symptoms. Screening for symptoms of mood, anxiety, and substance use disorders also can help reveal the nature of their presenting problem. If your adolescent patient is using drugs, that does not rule out the possibility of an underlying mood, anxiety, or thought disorder. While intoxication with many drugs may precipitate psychotic symptoms (including stimulants, hallucinogens, and marijuana), others may precipitate psychosis in withdrawal states (alcohol, benzodiazepines, and other CNS depressants). It also is important to note that adolescents with emerging schizophrenia have very high rates of comorbid substance abuse (as high as 60%), so their drug use may not be the cause of their psychotic symptoms. There also is emerging evidence that use of certain drugs during sensitive developmental periods can significantly increase the likelihood of developing schizophrenia in vulnerable populations, such as with regular marijuana use in adolescents who have a family history of schizophrenia.

For those rare pediatric patients who present with both negative and positive symptoms of emerging schizophrenia, early diagnosis and treatment has shown promise in improving the course of the disease. Cognitive-behavioral therapy (CBT) for psychosis has shown promise in lowering the rates of conversion to schizophrenia in select patient populations. This therapy teaches strategies for improving reality testing, cognitive flexibility, and social skills. The social skills appear to be especially important for improving adaptive function, even in those patients who progress to schizophrenia. Family therapies, focused on improving family cohesion, communication, and adaptive functioning, appear to improve family well-being and the course of the patient’s illness (such as fewer and less severe psychotic episodes and improved mood and adaptive function). Early use of antipsychotic medications also appears to improve the course of the illness.

While schizophrenia is not curable, early detection (perhaps by a pediatrician), referral, and treatment can be powerfully protective for patients and their families.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Psychol Med. 2012 Sep;42(9):1857-63.

2. Br J Psychiatry. 2012 Jul;201(1):26-32.

Strong feelings – such as intense anxiety, irritability, or depressed mood – may affect every child for brief periods of time during their development. Parents and pediatricians are wise to not treat them as psychiatric disorders unless they persist for weeks, impair functioning, or are dramatically severe. Psychosis – marked by hallucinations, perceptual distortions, or profoundly disorganized thinking and behavior – typically looks dramatically severe. Even when psychotic symptoms are mild or brief, they can cause very serious distress for parents and clinicians. The worry is that they may represent a “first break,” a psychotic episode that requires much work for recovery, or the beginning of a lifelong struggle with schizophrenia or other chronic psychotic illness.

KatarzynaBialasiewicz/iStock/Getty Images Plus

While it is important to recognize schizophrenia early – because early interventions are thought to improve the course of the disease – schizophrenia in childhood is rare. It is not commonly recognized that psychotic or psychoticlike symptoms are much more common than schizophrenia. In childhood, psychosis is three times more common than in adults, and can indicate a number of different psychiatric or medical problems. While it is important to begin a thoughtful evaluation when a child or teenager presents with psychosis, it also is important to know that the majority of young people who experience psychotic symptoms do not have schizophrenia or other psychotic illness.

Psychosis describes symptoms in which there has been some “break with reality,” often in the form of hallucinations (seeing or hearing things which are not objectively present) or of distorted perceptions (such as paranoia or grandiosity). “Subsyndromal psychotic symptoms” occur when a person experiences these perceptual disturbances but has doubt about whether or not they are real. In frank psychosis, patients have a “fixed and firm” belief in the truth or accuracy of their perceptions, no matter the evidence against them. The voices they hear or hallucinations they see are “real” and there is a wholehearted belief that what the voice says or what they are seeing is as true as what you or I see and hear.

Schizophrenia is a diagnosis that requires the presence of both these “positive” psychotic symptoms and “negative” symptoms of flat affect; loss of motivation, social, or motor abilities; and cognitive impairment. These symptoms typically emerge in late adolescence (median age, 18 years) in males and early adulthood (median age, 25 years) in females, with another (smaller) peak in incidence in middle age. Importantly, the negative symptoms often emerge first so there often is a history of subtle cognitive decline and social withdrawal, one of the most common patterns in children, before psychosis emerges. Schizophrenia is quite rare, with a prevalence of slightly under 1% of the global population, an annual incidence of approximately 15 people per 100,000, and 1 in 40,000 in children under 13 years old, according to the National Institute of Mental Health. Psychotic symptoms are much more common than schizophrenia, affecting approximately 5% of the adult population at any point in time. They are even more common in children and adolescents. A meta-analysis of population-based studies of psychotic symptoms in youth demonstrated a median prevalence of 17% in children aged 9-12 years and 7.5% in adolescents aged 13-18 years.¹ Of course, as with all statistics, much depends on the definitions used to identify this high prevalence rate.

Children and adolescents who report psychotic symptoms are at increased risk for developing schizophrenia, compared with the general population, but most youth with psychotic symptoms will not go on to develop schizophrenia. They are more likely to indicate other, nonpsychotic psychiatric illnesses, such as anxiety or mood disorders, including depression, obsessive compulsive disorder (OCD), and PTSD. In younger children, these symptoms may prove to be benign, but in adolescents they usually indicate the presence of a psychiatric illness. In one study, 57% of children aged 11-13 years with psychotic symptoms were found to have a nonpsychotic psychiatric illness, but the rate jumped to 80% for those aged 13-15 years with psychotic symptoms.² So while psychosis in teenagers only rarely indicates schizophrenia, these symptoms usually indicate the presence of a psychiatric illness, and a psychiatric evaluation should be initiated.

If a child in your practice presents with psychotic symptoms, it is appropriate to assess their safety and then start a medical work-up. Find out from your patient or their parents if their behavior has been affected by their perceptual disturbances. Are they frightened and avoiding school? Are they withdrawing from social relationships? Is their sleep disrupted? Have they been more impulsive or unpredictable? If their behavior has been affected, you should refer to a child psychiatrist to perform a full diagnostic evaluation and help with management of these symptoms.

Your medical work-up should include a drug screen, blood count, metabolic panel, and thyroid function test. Medications, particularly stimulants, steroids, and anticholinergics can cause psychotic symptoms in high doses or vulnerable patients (such as those with a developmental disorder or traumatic brain injury). If the physical or neurologic exam are suggestive, further investigation of the many potential medical sources of psychotic symptoms in youth can be pursued to rule out autoimmune illnesses, endocrine disorders, metabolic illnesses, heavy metal poisoning, neurologic diseases, infectious diseases, and nutritional deficits. It is worth noting that childhood sleep disorders also can present with psychosis. Persistent psychotic symptoms in children are very hard to evaluate and may be the harbinger of a serious psychiatric disorder, so even if the medical work-up is negative and the persistent symptoms are mild and not causing a safety concern, a referral to a child psychiatrist for a full mental health evaluation is appropriate.

Psychotic symptoms in an adolescent sometimes are easier to assess, more worrisome for serious mental illness, and are a high-risk category for self-destructive behavior and substance use. Before you begin a medical work-up, you always should assess for safety, including suicide risk, if your adolescent patient presents with psychotic symptoms. Screening for symptoms of mood, anxiety, and substance use disorders also can help reveal the nature of their presenting problem. If your adolescent patient is using drugs, that does not rule out the possibility of an underlying mood, anxiety, or thought disorder. While intoxication with many drugs may precipitate psychotic symptoms (including stimulants, hallucinogens, and marijuana), others may precipitate psychosis in withdrawal states (alcohol, benzodiazepines, and other CNS depressants). It also is important to note that adolescents with emerging schizophrenia have very high rates of comorbid substance abuse (as high as 60%), so their drug use may not be the cause of their psychotic symptoms. There also is emerging evidence that use of certain drugs during sensitive developmental periods can significantly increase the likelihood of developing schizophrenia in vulnerable populations, such as with regular marijuana use in adolescents who have a family history of schizophrenia.

For those rare pediatric patients who present with both negative and positive symptoms of emerging schizophrenia, early diagnosis and treatment has shown promise in improving the course of the disease. Cognitive-behavioral therapy (CBT) for psychosis has shown promise in lowering the rates of conversion to schizophrenia in select patient populations. This therapy teaches strategies for improving reality testing, cognitive flexibility, and social skills. The social skills appear to be especially important for improving adaptive function, even in those patients who progress to schizophrenia. Family therapies, focused on improving family cohesion, communication, and adaptive functioning, appear to improve family well-being and the course of the patient’s illness (such as fewer and less severe psychotic episodes and improved mood and adaptive function). Early use of antipsychotic medications also appears to improve the course of the illness.

While schizophrenia is not curable, early detection (perhaps by a pediatrician), referral, and treatment can be powerfully protective for patients and their families.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Psychol Med. 2012 Sep;42(9):1857-63.

2. Br J Psychiatry. 2012 Jul;201(1):26-32.

BARCELONA – A progressive aerobic and resistance exercise intervention improved the android:gynoid fat ratio (AGFR) in breast cancer survivors, which could provide important health benefits.

AGFR is associated with increased risk for cardiovascular disease and type 2 diabetes in breast cancer survivors, therefore exercise-induced AGFR improvement may reduce the risk for such comorbid conditions, Christina Dieli-Conwright, PhD, of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and colleagues reported in a poster at the European Society for Medical Oncology Congress.

A significant decrease in AGFR from baseline was noted in 50 survivors of stage I-III breast cancer who participated in the exercise intervention, compared with 50 such survivors randomized to a usual care group (P less than .001), and strong correlations were found between AGFR and homeostatic model assessment of insulin resistance (HOMA-IR; r = 0.95; P less than .01), the investigators found.

Study participants had a mean age of 53 years, 54% were overweight (body mass index greater than 25 kg/m²), 63% were Hispanic, 90% had undergone a mastectomy, and 76% received chemotherapy and radiation therapy. Adherence to the intervention, which involved three weekly sessions of supervised, progressive, moderate-to-vigorous aerobic and resistance exercise for 16 weeks, was 95%.

AGFR was calculated using whole-body dual-energy x-ray absorptiometry and HOMA-IR was calculated using fasting insulin and glucose levels.

“Exercise reduces fat mass in breast cancer survivors, however, few studies have focused on AGFR,” the investigators wrote.

The findings of the current study suggest that a progressive aerobic and resistance exercise intervention is an effective strategy for decreasing AGFR in breast cancer survivors, they concluded.

The National Cancer Institute funded the study. The authors reported having no disclosures.

SOURCE: Dieli-Conwright C et al. ESMO 2019, Abstract 228P.

BARCELONA – A progressive aerobic and resistance exercise intervention improved the android:gynoid fat ratio (AGFR) in breast cancer survivors, which could provide important health benefits.

AGFR is associated with increased risk for cardiovascular disease and type 2 diabetes in breast cancer survivors, therefore exercise-induced AGFR improvement may reduce the risk for such comorbid conditions, Christina Dieli-Conwright, PhD, of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and colleagues reported in a poster at the European Society for Medical Oncology Congress.

A significant decrease in AGFR from baseline was noted in 50 survivors of stage I-III breast cancer who participated in the exercise intervention, compared with 50 such survivors randomized to a usual care group (P less than .001), and strong correlations were found between AGFR and homeostatic model assessment of insulin resistance (HOMA-IR; r = 0.95; P less than .01), the investigators found.

Study participants had a mean age of 53 years, 54% were overweight (body mass index greater than 25 kg/m²), 63% were Hispanic, 90% had undergone a mastectomy, and 76% received chemotherapy and radiation therapy. Adherence to the intervention, which involved three weekly sessions of supervised, progressive, moderate-to-vigorous aerobic and resistance exercise for 16 weeks, was 95%.

AGFR was calculated using whole-body dual-energy x-ray absorptiometry and HOMA-IR was calculated using fasting insulin and glucose levels.

“Exercise reduces fat mass in breast cancer survivors, however, few studies have focused on AGFR,” the investigators wrote.

The findings of the current study suggest that a progressive aerobic and resistance exercise intervention is an effective strategy for decreasing AGFR in breast cancer survivors, they concluded.

The National Cancer Institute funded the study. The authors reported having no disclosures.

SOURCE: Dieli-Conwright C et al. ESMO 2019, Abstract 228P.

BARCELONA – A progressive aerobic and resistance exercise intervention improved the android:gynoid fat ratio (AGFR) in breast cancer survivors, which could provide important health benefits.

AGFR is associated with increased risk for cardiovascular disease and type 2 diabetes in breast cancer survivors, therefore exercise-induced AGFR improvement may reduce the risk for such comorbid conditions, Christina Dieli-Conwright, PhD, of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and colleagues reported in a poster at the European Society for Medical Oncology Congress.

A significant decrease in AGFR from baseline was noted in 50 survivors of stage I-III breast cancer who participated in the exercise intervention, compared with 50 such survivors randomized to a usual care group (P less than .001), and strong correlations were found between AGFR and homeostatic model assessment of insulin resistance (HOMA-IR; r = 0.95; P less than .01), the investigators found.

Study participants had a mean age of 53 years, 54% were overweight (body mass index greater than 25 kg/m²), 63% were Hispanic, 90% had undergone a mastectomy, and 76% received chemotherapy and radiation therapy. Adherence to the intervention, which involved three weekly sessions of supervised, progressive, moderate-to-vigorous aerobic and resistance exercise for 16 weeks, was 95%.

AGFR was calculated using whole-body dual-energy x-ray absorptiometry and HOMA-IR was calculated using fasting insulin and glucose levels.

“Exercise reduces fat mass in breast cancer survivors, however, few studies have focused on AGFR,” the investigators wrote.

The findings of the current study suggest that a progressive aerobic and resistance exercise intervention is an effective strategy for decreasing AGFR in breast cancer survivors, they concluded.

The National Cancer Institute funded the study. The authors reported having no disclosures.

SOURCE: Dieli-Conwright C et al. ESMO 2019, Abstract 228P.

When I started at the Society of Hospital Medicine – known then as the National Association of Inpatient Physicians (NAIP) – in January 2000, Bill Clinton was still president. There were probably 500 hospitalists in the United States, and SHM had about 200-250 members.

It was so long ago that the iPhone hadn’t been invented, Twitter wasn’t even an idea, and Amazon was an online book store. SHM’s national offices were a cubicle at the American College of Physicians headquarters in Philadelphia, and our entire staff was me and a part-time assistant.

We have certainly come a long way in my 20 years as CEO of SHM.

When I first became involved with NAIP, it was to help the board with their strategic planning in 1998. At that time, the national thought leaders for the hospitalist movement (the term hospital medicine had not been invented yet) predicted that hospitalists would eventually do the inpatient work for about 25% of family doctors and for 15% of internists. Hospitalists were considered to be a form of “general medicine” without an office-based practice.

One of the first things we set about doing was to define the new specialty of hospital medicine before anyone else (e.g., American Medical Association, ACP, American Academy of Family Physicians, American Academy of Pediatrics, the government) defined us.

Most specialties were defined by a body organ (e.g., cardiology, renal), a population (e.g., pediatrics, geriatrics), or a disease (e.g., oncology), and there were a few other site-specific specialties (e.g., ED medicine, critical care). We felt that, to be a specialty, we needed certain key elements:

• Separate group consciousness
• Professional society
• Distinct residency and fellowship programs
• Separate CME
• Distinct educational materials (e.g., textbooks)
• Definable and distinct competencies
• Separate credentials – certification and/or hospital insurance driven

Early on, SHM defined the Core Competencies for Hospital Medicine for adults in patient care and, eventually, for pediatric patients. We rebranded our specialty as hospital medicine to be more than just inpatient physicians, and to broadly encompass the growing “big tent” of SHM that included those trained in internal medicine, family medicine, pediatrics, med-peds, as well as nurse practitioners, physician assistants, pharmacists, and others.

We were the first and only specialty society to set the standard for hospitalist compensation (how much you are paid) and productivity (what you are expected to do) with our unique State of Hospital Medicine (SOHM) Report. Other specialties left this work to the Medical Group Management Association, the AMA, or commercial companies.

Our specialty was soon being asked to do things that no other group of clinicians was ever asked to do.

Hospitalists were expected to Save Money by reducing length of stay and the use of resources on the sickest patients. Hospitalists were asked to Improve Measurable Quality at a time when most other physicians or even hospitals weren’t even being measured.

We were expected to form and Lead Teams of other clinicians when health care was still seen as a solo enterprise. Hospitalists were expected to Improve Efficiency and to create a Seamless Continuity, both during the hospital stay and in the transitions out of the hospital.

Hospitalists were asked to do things no one else wanted to do, such as taking on the uncompensated patients and extra hospital committee work and just about any new project their hospital wanted to be involved in. Along the way, we were expected to Make Other Physicians’ Lives Better by taking on their inpatients, inpatient calls, comanagement with specialists, and unloading the ED.

And both at medical schools and in the community, hospitalists became the Major Educators of medical students, residents, nurses, and other hospital staff.

At the same time, SHM was focusing on becoming a very unique medical professional society.

SHM built on the energy of our young and innovative hospitalists to forge a different path. We had no reputation to protect. We were not bound like most other specialty societies to over 100 years of “the way it’s always been done.”

While other professional societies thought their role in quality improvement was to pontificate and publish clinical guidelines that often were little used, SHM embarked on an aggressive, hands-on, frontline approach by starting SHM’s Center for Quality Improvement. Over the last 15 years, the center has raised millions of dollars to deliver real change and improvement at hundreds of hospitals nationwide, many times bringing work plans and mentors to support and train local clinicians in quality improvement skills and data collection. This approach was recognized by the National Quality Forum and the Joint Commission with their prestigious John Eisenberg Award for Quality Improvement.

When we went to Washington to help shape the future of health care, we did not ask for more money for hospitalists. We did not ask for more power or to use regulations to protect our new specialty. Instead, we went with ideas of how to make acute medical care more effective and efficient. We could show the politicians and the regulators how we could reduce incidence of deep vein thrombosis and pulmonary emboli, how we could make the hospital discharge process work better, how we could help chart a smoother medication reconciliation process, and so many other ways the system could be improved.

And even the way SHM generated our new ideas was uniquely different than other specialties. Way back in 2000 – long before Twitter and other social media were able to crowdsource and use the Internet to percolate new ideas – SHM relied on our members’ conversations on the SHM electronic mail discussion list to see what hospitalists were worried about, and what everyone was being asked to do, and SHM provided the resources and initiatives to support our nation’s hospitalists.

From these early conversations, SHM heard that hospitalists were being asked to Lead Change without much of an idea of the skills they would need. And so, the SHM leadership academies were born, which have now educated more than 2,700 hospitalist leaders.

Early on, we learned that hospitalists and even their bosses had no idea of how to start or run a successful hospital medicine group. SHM started our practice management courses and webinars and we developed the groundbreaking document, Key Characteristics of Effective Hospital Medicine Groups. In a typical SHM manner, we challenged most of our members to improve and get better rather trying to defend the status quo. At SHM, we have constantly felt that hospital medicine was a “work in progress.” We may not be perfect today, but we will be better in 90 days and even better in a year.

I have more to say about how we got this far and even more to say about where we might go. So, stay tuned and keep contributing to the future and success of SHM and hospital medicine.

Dr. Wellikson is the CEO of SHM. He has announced his plan to retire from SHM in late 2020. This article is the first in a series celebrating Dr. Wellikson’s tenure as CEO.

When I started at the Society of Hospital Medicine – known then as the National Association of Inpatient Physicians (NAIP) – in January 2000, Bill Clinton was still president. There were probably 500 hospitalists in the United States, and SHM had about 200-250 members.

It was so long ago that the iPhone hadn’t been invented, Twitter wasn’t even an idea, and Amazon was an online book store. SHM’s national offices were a cubicle at the American College of Physicians headquarters in Philadelphia, and our entire staff was me and a part-time assistant.

We have certainly come a long way in my 20 years as CEO of SHM.

When I first became involved with NAIP, it was to help the board with their strategic planning in 1998. At that time, the national thought leaders for the hospitalist movement (the term hospital medicine had not been invented yet) predicted that hospitalists would eventually do the inpatient work for about 25% of family doctors and for 15% of internists. Hospitalists were considered to be a form of “general medicine” without an office-based practice.

One of the first things we set about doing was to define the new specialty of hospital medicine before anyone else (e.g., American Medical Association, ACP, American Academy of Family Physicians, American Academy of Pediatrics, the government) defined us.

Most specialties were defined by a body organ (e.g., cardiology, renal), a population (e.g., pediatrics, geriatrics), or a disease (e.g., oncology), and there were a few other site-specific specialties (e.g., ED medicine, critical care). We felt that, to be a specialty, we needed certain key elements:

• Separate group consciousness
• Professional society
• Distinct residency and fellowship programs
• Separate CME
• Distinct educational materials (e.g., textbooks)
• Definable and distinct competencies
• Separate credentials – certification and/or hospital insurance driven

Early on, SHM defined the Core Competencies for Hospital Medicine for adults in patient care and, eventually, for pediatric patients. We rebranded our specialty as hospital medicine to be more than just inpatient physicians, and to broadly encompass the growing “big tent” of SHM that included those trained in internal medicine, family medicine, pediatrics, med-peds, as well as nurse practitioners, physician assistants, pharmacists, and others.

We were the first and only specialty society to set the standard for hospitalist compensation (how much you are paid) and productivity (what you are expected to do) with our unique State of Hospital Medicine (SOHM) Report. Other specialties left this work to the Medical Group Management Association, the AMA, or commercial companies.

Our specialty was soon being asked to do things that no other group of clinicians was ever asked to do.

Hospitalists were expected to Save Money by reducing length of stay and the use of resources on the sickest patients. Hospitalists were asked to Improve Measurable Quality at a time when most other physicians or even hospitals weren’t even being measured.

We were expected to form and Lead Teams of other clinicians when health care was still seen as a solo enterprise. Hospitalists were expected to Improve Efficiency and to create a Seamless Continuity, both during the hospital stay and in the transitions out of the hospital.

Hospitalists were asked to do things no one else wanted to do, such as taking on the uncompensated patients and extra hospital committee work and just about any new project their hospital wanted to be involved in. Along the way, we were expected to Make Other Physicians’ Lives Better by taking on their inpatients, inpatient calls, comanagement with specialists, and unloading the ED.

And both at medical schools and in the community, hospitalists became the Major Educators of medical students, residents, nurses, and other hospital staff.

At the same time, SHM was focusing on becoming a very unique medical professional society.

SHM built on the energy of our young and innovative hospitalists to forge a different path. We had no reputation to protect. We were not bound like most other specialty societies to over 100 years of “the way it’s always been done.”

While other professional societies thought their role in quality improvement was to pontificate and publish clinical guidelines that often were little used, SHM embarked on an aggressive, hands-on, frontline approach by starting SHM’s Center for Quality Improvement. Over the last 15 years, the center has raised millions of dollars to deliver real change and improvement at hundreds of hospitals nationwide, many times bringing work plans and mentors to support and train local clinicians in quality improvement skills and data collection. This approach was recognized by the National Quality Forum and the Joint Commission with their prestigious John Eisenberg Award for Quality Improvement.

When we went to Washington to help shape the future of health care, we did not ask for more money for hospitalists. We did not ask for more power or to use regulations to protect our new specialty. Instead, we went with ideas of how to make acute medical care more effective and efficient. We could show the politicians and the regulators how we could reduce incidence of deep vein thrombosis and pulmonary emboli, how we could make the hospital discharge process work better, how we could help chart a smoother medication reconciliation process, and so many other ways the system could be improved.

And even the way SHM generated our new ideas was uniquely different than other specialties. Way back in 2000 – long before Twitter and other social media were able to crowdsource and use the Internet to percolate new ideas – SHM relied on our members’ conversations on the SHM electronic mail discussion list to see what hospitalists were worried about, and what everyone was being asked to do, and SHM provided the resources and initiatives to support our nation’s hospitalists.

From these early conversations, SHM heard that hospitalists were being asked to Lead Change without much of an idea of the skills they would need. And so, the SHM leadership academies were born, which have now educated more than 2,700 hospitalist leaders.

Early on, we learned that hospitalists and even their bosses had no idea of how to start or run a successful hospital medicine group. SHM started our practice management courses and webinars and we developed the groundbreaking document, Key Characteristics of Effective Hospital Medicine Groups. In a typical SHM manner, we challenged most of our members to improve and get better rather trying to defend the status quo. At SHM, we have constantly felt that hospital medicine was a “work in progress.” We may not be perfect today, but we will be better in 90 days and even better in a year.

I have more to say about how we got this far and even more to say about where we might go. So, stay tuned and keep contributing to the future and success of SHM and hospital medicine.

Dr. Wellikson is the CEO of SHM. He has announced his plan to retire from SHM in late 2020. This article is the first in a series celebrating Dr. Wellikson’s tenure as CEO.

When I started at the Society of Hospital Medicine – known then as the National Association of Inpatient Physicians (NAIP) – in January 2000, Bill Clinton was still president. There were probably 500 hospitalists in the United States, and SHM had about 200-250 members.

It was so long ago that the iPhone hadn’t been invented, Twitter wasn’t even an idea, and Amazon was an online book store. SHM’s national offices were a cubicle at the American College of Physicians headquarters in Philadelphia, and our entire staff was me and a part-time assistant.

We have certainly come a long way in my 20 years as CEO of SHM.

When I first became involved with NAIP, it was to help the board with their strategic planning in 1998. At that time, the national thought leaders for the hospitalist movement (the term hospital medicine had not been invented yet) predicted that hospitalists would eventually do the inpatient work for about 25% of family doctors and for 15% of internists. Hospitalists were considered to be a form of “general medicine” without an office-based practice.

One of the first things we set about doing was to define the new specialty of hospital medicine before anyone else (e.g., American Medical Association, ACP, American Academy of Family Physicians, American Academy of Pediatrics, the government) defined us.

Most specialties were defined by a body organ (e.g., cardiology, renal), a population (e.g., pediatrics, geriatrics), or a disease (e.g., oncology), and there were a few other site-specific specialties (e.g., ED medicine, critical care). We felt that, to be a specialty, we needed certain key elements:

• Separate group consciousness
• Professional society
• Distinct residency and fellowship programs
• Separate CME
• Distinct educational materials (e.g., textbooks)
• Definable and distinct competencies
• Separate credentials – certification and/or hospital insurance driven

Early on, SHM defined the Core Competencies for Hospital Medicine for adults in patient care and, eventually, for pediatric patients. We rebranded our specialty as hospital medicine to be more than just inpatient physicians, and to broadly encompass the growing “big tent” of SHM that included those trained in internal medicine, family medicine, pediatrics, med-peds, as well as nurse practitioners, physician assistants, pharmacists, and others.

We were the first and only specialty society to set the standard for hospitalist compensation (how much you are paid) and productivity (what you are expected to do) with our unique State of Hospital Medicine (SOHM) Report. Other specialties left this work to the Medical Group Management Association, the AMA, or commercial companies.

Our specialty was soon being asked to do things that no other group of clinicians was ever asked to do.

Hospitalists were expected to Save Money by reducing length of stay and the use of resources on the sickest patients. Hospitalists were asked to Improve Measurable Quality at a time when most other physicians or even hospitals weren’t even being measured.

We were expected to form and Lead Teams of other clinicians when health care was still seen as a solo enterprise. Hospitalists were expected to Improve Efficiency and to create a Seamless Continuity, both during the hospital stay and in the transitions out of the hospital.

Hospitalists were asked to do things no one else wanted to do, such as taking on the uncompensated patients and extra hospital committee work and just about any new project their hospital wanted to be involved in. Along the way, we were expected to Make Other Physicians’ Lives Better by taking on their inpatients, inpatient calls, comanagement with specialists, and unloading the ED.

And both at medical schools and in the community, hospitalists became the Major Educators of medical students, residents, nurses, and other hospital staff.

At the same time, SHM was focusing on becoming a very unique medical professional society.

SHM built on the energy of our young and innovative hospitalists to forge a different path. We had no reputation to protect. We were not bound like most other specialty societies to over 100 years of “the way it’s always been done.”

While other professional societies thought their role in quality improvement was to pontificate and publish clinical guidelines that often were little used, SHM embarked on an aggressive, hands-on, frontline approach by starting SHM’s Center for Quality Improvement. Over the last 15 years, the center has raised millions of dollars to deliver real change and improvement at hundreds of hospitals nationwide, many times bringing work plans and mentors to support and train local clinicians in quality improvement skills and data collection. This approach was recognized by the National Quality Forum and the Joint Commission with their prestigious John Eisenberg Award for Quality Improvement.

When we went to Washington to help shape the future of health care, we did not ask for more money for hospitalists. We did not ask for more power or to use regulations to protect our new specialty. Instead, we went with ideas of how to make acute medical care more effective and efficient. We could show the politicians and the regulators how we could reduce incidence of deep vein thrombosis and pulmonary emboli, how we could make the hospital discharge process work better, how we could help chart a smoother medication reconciliation process, and so many other ways the system could be improved.

And even the way SHM generated our new ideas was uniquely different than other specialties. Way back in 2000 – long before Twitter and other social media were able to crowdsource and use the Internet to percolate new ideas – SHM relied on our members’ conversations on the SHM electronic mail discussion list to see what hospitalists were worried about, and what everyone was being asked to do, and SHM provided the resources and initiatives to support our nation’s hospitalists.

From these early conversations, SHM heard that hospitalists were being asked to Lead Change without much of an idea of the skills they would need. And so, the SHM leadership academies were born, which have now educated more than 2,700 hospitalist leaders.

Early on, we learned that hospitalists and even their bosses had no idea of how to start or run a successful hospital medicine group. SHM started our practice management courses and webinars and we developed the groundbreaking document, Key Characteristics of Effective Hospital Medicine Groups. In a typical SHM manner, we challenged most of our members to improve and get better rather trying to defend the status quo. At SHM, we have constantly felt that hospital medicine was a “work in progress.” We may not be perfect today, but we will be better in 90 days and even better in a year.

I have more to say about how we got this far and even more to say about where we might go. So, stay tuned and keep contributing to the future and success of SHM and hospital medicine.

Dr. Wellikson is the CEO of SHM. He has announced his plan to retire from SHM in late 2020. This article is the first in a series celebrating Dr. Wellikson’s tenure as CEO.

ORLANDO – Cumulative evidence over the years has shown that bisphosphonates reduce distant metastases in postmenopausal women with early-stage breast cancer but that effect does not seem to extend to younger, premenopausal women who may experience adverse effects with bisphosphonates, nor has it been replicated in other types of cancer, such as lung or prostate, Robert Coleman MBBS, MD, said in a presentation marking the 50th anniversary of the publication of the first papers describing the then-new class of drugs.

“We have some science – at least in postmenopausal breast cancer – [showing] that we’re really making a difference, but we don’t understand why it’s not working in the other patients or in the other diseases,” said Dr. Coleman of the University of Sheffield (England) at the annual meeting of the American Society for Bone and Mineral Research.
 

Mixed findings in early studies

Early studies showing the metastases-prevention effects of bisphosphonates were with clodronate. In one study, Dr. Coleman said, researchers found that oral clodronate at a dose of 1,600 mg/day as a supplementary treatment to standard treatment for primary, operable breast cancer reduced the risk of bone metastases in a cohort of 1,069 patients with stage 1-3 breast cancer (hazard ratio, 0.692; P = .043) over 5 years (Breast Cancer Res. 2006 Mar 15. doi: 10.1186/bcr1384). Another trial, of 302 patients with breast cancer who received oral clodronate at 1,600 mg/day for 2 years, found that 20.4% of patients who received oral clodronate had died by 8.5 years of follow-up, compared with 40.7% of those who did not receive the intervention (Ann Oncol. 2008;19[12]:2007-11).

However, those results were in conflict with findings from an earlier study in which researchers followed patients with breast cancer who received 1,600 mg/day of oral clodronate or placebo for 3 years. They found a similar number of bone metastases in the clodronate and placebo groups (32% and 29%, respectively), as well as a lower overall disease-free survival rate at 10 years for the clodronate group, compared with the placebo group (45% vs. 58%; Acta Oncol. 2004;43[7]:650-6).“For various other reasons, clodronate did not gain traction as a therapeutic strategy in early-stage breast cancer,” said Dr. Coleman, although emerging evidence showed that other bisphosphonate agents were effective in some patients with breast cancer.

In a 2009 article, Gnant et al. reported that premenopausal patients, who underwent primary surgery for stage 1 or stage 2 breast cancer and received standard goserelin therapy for induced menopause and endocrine therapy (either tamoxifen or anastrozole) in addition to treatment with zoledronic acid, had a disease-free survival rate of 94.0% at a median 47.8 months of follow-up (N Eng J Med. 2009;360:679-91). After a median 94.4 months of follow-up, the investigators reported a lower risk of disease progression (HR, 0.77; 95% confidence interval, 0.60-0.99; P = .042) and death (HR, 0.66; 95% CI, 0.43-1.02; P = .064; Ann Oncol. 2015;26[2]:313-20).

In his own group, Dr. Coleman and colleagues recruited patients with early-stage breast cancer in the AZURE trial, a phase 3 study of 3,360 patients who received standard therapy with or without zoledronic acid 4 mg every 3-4 weeks for 6 doses, followed by 8 doses every 3 months then 5 doses every 6 months (N Eng J Med. 2011;365:1396-405). “We saw no effect,” said Dr. Coleman. “[That was] very different from what was shown by [Dr.] Gnant.”

For a subgroup of postmenopausal patients, Dr. Coleman and colleagues found that the adjusted HR for disease-free survival was 0.82 for women who were more than 5 years postmenopausal (95% CI, 0.67-1.00) at the time of breast cancer and bisphosphonate treatment, but women younger than 40 years had worse survival outcomes at 10 years (HR, 1.56; 95% CI, 1.09-2.22) and had a significantly higher risk of death from breast cancer (HR, 1.67; 95% CI, 1.16-2.40; J Bone Oncol. 2018 Sep 27. doi: 10.1016/j.jbo.2018.09.008).
 

Trying to reconcile disparate findings

Those findings left his group with a dilemma, said Dr. Coleman. “Do we start again and run trials, and wait another 10 years, or is there a shortcut to [understanding] what’s going on?” he asked.

In a meta-analysis of all trials from the Early Breast Cancer Trialists’ Collaborative Group in 2015 examining adjuvant bisphosphonate treatment and placebo in patients with early-stage breast cancer, intent-to-treat analyses did not show significant benefit after therapy, but postmenopausal women (11,767 women in 36 trials) saw a clear benefit in all recurrence (rate ratio, 0.86; 95% CI, 0.78-0.94), bone recurrence (RR, 0.72; 95% CI, 0.60-0.86), and breast cancer–related mortality (RR, 0.82; 95% CI, 0.73-0.93; Lancet. 2015 Jul 23. doi: 10.1016/S0140-6736[15]60908-4). The effect seemed to be similar, regardless of bisphosphonate type, with other results seen across trials that used clodronate, zoledronic acid, pamidronate, or ibandronate.

“Although those outcome differences might look quite small for a common disease, that’s a really big effect. Reducing one-sixth of breast cancer deaths at 10 years is the equivalent of saving 10,000 lives across the [European Union], and about half that in the United States,” said Dr. Coleman, noting that guidelines in North America from the American Society of Clinical Oncology and the European Society for Medical Oncology now support adjuvant bisphosphonates in postmenopausal patients with breast cancer.

However, bisphosphonates’ effect on breast cancer does not extend to other cancers, such as non–small cell lung cancer or prostate cancer. In other absorption inhibitors such as denosumab, there also seems to be no benefit for patients with breast cancer, including in postmenopausal patient subgroups, said Dr. Coleman. “In my view, osteoclast inhibition is only part of the story,” he noted.

In the AZURE trial, secondary outcomes examined how the transcription factor MAF interacted with menopausal status and treatment with zoledronic acid. The 79% of patients with tumors that were negative for MAF fluorescence in situ hybridization had improved overall survival (0.69; 95% CI, 0.50-0.94), regardless of menopause status (J Bone Oncol. 2018. doi: 10.1016/j.jbo.2018.09.008). “There’s probably a need to merge the treatment: in this case, the bisphosphonate, the biology of the cancer, and the environment the cancer finds itself in,” noted Dr. Coleman.

“From the cancer perspective, bisphosphonates have transformed the experience for many of our patients with advanced disease, and now we’re working to see great improvements, at least in common diseases such as postmenopausal breast cancer,” he concluded.

Dr. Coleman reports being a paid employee of prIME Oncology (until March 2019); is a consultant for Amgen, Astellas, Boehringer Ingelheim, Scandell, and Biocon; is on the speakers bureau for Amgen and Eisai; holds intellectual property rights for a biomarker being developed by Inbiomotion; and is on the scientific advisory board for Inbiomotion.

ORLANDO – Cumulative evidence over the years has shown that bisphosphonates reduce distant metastases in postmenopausal women with early-stage breast cancer but that effect does not seem to extend to younger, premenopausal women who may experience adverse effects with bisphosphonates, nor has it been replicated in other types of cancer, such as lung or prostate, Robert Coleman MBBS, MD, said in a presentation marking the 50th anniversary of the publication of the first papers describing the then-new class of drugs.

“We have some science – at least in postmenopausal breast cancer – [showing] that we’re really making a difference, but we don’t understand why it’s not working in the other patients or in the other diseases,” said Dr. Coleman of the University of Sheffield (England) at the annual meeting of the American Society for Bone and Mineral Research.
 

Mixed findings in early studies

Early studies showing the metastases-prevention effects of bisphosphonates were with clodronate. In one study, Dr. Coleman said, researchers found that oral clodronate at a dose of 1,600 mg/day as a supplementary treatment to standard treatment for primary, operable breast cancer reduced the risk of bone metastases in a cohort of 1,069 patients with stage 1-3 breast cancer (hazard ratio, 0.692; P = .043) over 5 years (Breast Cancer Res. 2006 Mar 15. doi: 10.1186/bcr1384). Another trial, of 302 patients with breast cancer who received oral clodronate at 1,600 mg/day for 2 years, found that 20.4% of patients who received oral clodronate had died by 8.5 years of follow-up, compared with 40.7% of those who did not receive the intervention (Ann Oncol. 2008;19[12]:2007-11).

However, those results were in conflict with findings from an earlier study in which researchers followed patients with breast cancer who received 1,600 mg/day of oral clodronate or placebo for 3 years. They found a similar number of bone metastases in the clodronate and placebo groups (32% and 29%, respectively), as well as a lower overall disease-free survival rate at 10 years for the clodronate group, compared with the placebo group (45% vs. 58%; Acta Oncol. 2004;43[7]:650-6).“For various other reasons, clodronate did not gain traction as a therapeutic strategy in early-stage breast cancer,” said Dr. Coleman, although emerging evidence showed that other bisphosphonate agents were effective in some patients with breast cancer.

In a 2009 article, Gnant et al. reported that premenopausal patients, who underwent primary surgery for stage 1 or stage 2 breast cancer and received standard goserelin therapy for induced menopause and endocrine therapy (either tamoxifen or anastrozole) in addition to treatment with zoledronic acid, had a disease-free survival rate of 94.0% at a median 47.8 months of follow-up (N Eng J Med. 2009;360:679-91). After a median 94.4 months of follow-up, the investigators reported a lower risk of disease progression (HR, 0.77; 95% confidence interval, 0.60-0.99; P = .042) and death (HR, 0.66; 95% CI, 0.43-1.02; P = .064; Ann Oncol. 2015;26[2]:313-20).

In his own group, Dr. Coleman and colleagues recruited patients with early-stage breast cancer in the AZURE trial, a phase 3 study of 3,360 patients who received standard therapy with or without zoledronic acid 4 mg every 3-4 weeks for 6 doses, followed by 8 doses every 3 months then 5 doses every 6 months (N Eng J Med. 2011;365:1396-405). “We saw no effect,” said Dr. Coleman. “[That was] very different from what was shown by [Dr.] Gnant.”

For a subgroup of postmenopausal patients, Dr. Coleman and colleagues found that the adjusted HR for disease-free survival was 0.82 for women who were more than 5 years postmenopausal (95% CI, 0.67-1.00) at the time of breast cancer and bisphosphonate treatment, but women younger than 40 years had worse survival outcomes at 10 years (HR, 1.56; 95% CI, 1.09-2.22) and had a significantly higher risk of death from breast cancer (HR, 1.67; 95% CI, 1.16-2.40; J Bone Oncol. 2018 Sep 27. doi: 10.1016/j.jbo.2018.09.008).
 

Trying to reconcile disparate findings

Those findings left his group with a dilemma, said Dr. Coleman. “Do we start again and run trials, and wait another 10 years, or is there a shortcut to [understanding] what’s going on?” he asked.

In a meta-analysis of all trials from the Early Breast Cancer Trialists’ Collaborative Group in 2015 examining adjuvant bisphosphonate treatment and placebo in patients with early-stage breast cancer, intent-to-treat analyses did not show significant benefit after therapy, but postmenopausal women (11,767 women in 36 trials) saw a clear benefit in all recurrence (rate ratio, 0.86; 95% CI, 0.78-0.94), bone recurrence (RR, 0.72; 95% CI, 0.60-0.86), and breast cancer–related mortality (RR, 0.82; 95% CI, 0.73-0.93; Lancet. 2015 Jul 23. doi: 10.1016/S0140-6736[15]60908-4). The effect seemed to be similar, regardless of bisphosphonate type, with other results seen across trials that used clodronate, zoledronic acid, pamidronate, or ibandronate.

“Although those outcome differences might look quite small for a common disease, that’s a really big effect. Reducing one-sixth of breast cancer deaths at 10 years is the equivalent of saving 10,000 lives across the [European Union], and about half that in the United States,” said Dr. Coleman, noting that guidelines in North America from the American Society of Clinical Oncology and the European Society for Medical Oncology now support adjuvant bisphosphonates in postmenopausal patients with breast cancer.

However, bisphosphonates’ effect on breast cancer does not extend to other cancers, such as non–small cell lung cancer or prostate cancer. In other absorption inhibitors such as denosumab, there also seems to be no benefit for patients with breast cancer, including in postmenopausal patient subgroups, said Dr. Coleman. “In my view, osteoclast inhibition is only part of the story,” he noted.

In the AZURE trial, secondary outcomes examined how the transcription factor MAF interacted with menopausal status and treatment with zoledronic acid. The 79% of patients with tumors that were negative for MAF fluorescence in situ hybridization had improved overall survival (0.69; 95% CI, 0.50-0.94), regardless of menopause status (J Bone Oncol. 2018. doi: 10.1016/j.jbo.2018.09.008). “There’s probably a need to merge the treatment: in this case, the bisphosphonate, the biology of the cancer, and the environment the cancer finds itself in,” noted Dr. Coleman.

“From the cancer perspective, bisphosphonates have transformed the experience for many of our patients with advanced disease, and now we’re working to see great improvements, at least in common diseases such as postmenopausal breast cancer,” he concluded.

Dr. Coleman reports being a paid employee of prIME Oncology (until March 2019); is a consultant for Amgen, Astellas, Boehringer Ingelheim, Scandell, and Biocon; is on the speakers bureau for Amgen and Eisai; holds intellectual property rights for a biomarker being developed by Inbiomotion; and is on the scientific advisory board for Inbiomotion.

ORLANDO – Cumulative evidence over the years has shown that bisphosphonates reduce distant metastases in postmenopausal women with early-stage breast cancer but that effect does not seem to extend to younger, premenopausal women who may experience adverse effects with bisphosphonates, nor has it been replicated in other types of cancer, such as lung or prostate, Robert Coleman MBBS, MD, said in a presentation marking the 50th anniversary of the publication of the first papers describing the then-new class of drugs.

“We have some science – at least in postmenopausal breast cancer – [showing] that we’re really making a difference, but we don’t understand why it’s not working in the other patients or in the other diseases,” said Dr. Coleman of the University of Sheffield (England) at the annual meeting of the American Society for Bone and Mineral Research.
 

Mixed findings in early studies

Early studies showing the metastases-prevention effects of bisphosphonates were with clodronate. In one study, Dr. Coleman said, researchers found that oral clodronate at a dose of 1,600 mg/day as a supplementary treatment to standard treatment for primary, operable breast cancer reduced the risk of bone metastases in a cohort of 1,069 patients with stage 1-3 breast cancer (hazard ratio, 0.692; P = .043) over 5 years (Breast Cancer Res. 2006 Mar 15. doi: 10.1186/bcr1384). Another trial, of 302 patients with breast cancer who received oral clodronate at 1,600 mg/day for 2 years, found that 20.4% of patients who received oral clodronate had died by 8.5 years of follow-up, compared with 40.7% of those who did not receive the intervention (Ann Oncol. 2008;19[12]:2007-11).

However, those results were in conflict with findings from an earlier study in which researchers followed patients with breast cancer who received 1,600 mg/day of oral clodronate or placebo for 3 years. They found a similar number of bone metastases in the clodronate and placebo groups (32% and 29%, respectively), as well as a lower overall disease-free survival rate at 10 years for the clodronate group, compared with the placebo group (45% vs. 58%; Acta Oncol. 2004;43[7]:650-6).“For various other reasons, clodronate did not gain traction as a therapeutic strategy in early-stage breast cancer,” said Dr. Coleman, although emerging evidence showed that other bisphosphonate agents were effective in some patients with breast cancer.

In a 2009 article, Gnant et al. reported that premenopausal patients, who underwent primary surgery for stage 1 or stage 2 breast cancer and received standard goserelin therapy for induced menopause and endocrine therapy (either tamoxifen or anastrozole) in addition to treatment with zoledronic acid, had a disease-free survival rate of 94.0% at a median 47.8 months of follow-up (N Eng J Med. 2009;360:679-91). After a median 94.4 months of follow-up, the investigators reported a lower risk of disease progression (HR, 0.77; 95% confidence interval, 0.60-0.99; P = .042) and death (HR, 0.66; 95% CI, 0.43-1.02; P = .064; Ann Oncol. 2015;26[2]:313-20).

In his own group, Dr. Coleman and colleagues recruited patients with early-stage breast cancer in the AZURE trial, a phase 3 study of 3,360 patients who received standard therapy with or without zoledronic acid 4 mg every 3-4 weeks for 6 doses, followed by 8 doses every 3 months then 5 doses every 6 months (N Eng J Med. 2011;365:1396-405). “We saw no effect,” said Dr. Coleman. “[That was] very different from what was shown by [Dr.] Gnant.”

For a subgroup of postmenopausal patients, Dr. Coleman and colleagues found that the adjusted HR for disease-free survival was 0.82 for women who were more than 5 years postmenopausal (95% CI, 0.67-1.00) at the time of breast cancer and bisphosphonate treatment, but women younger than 40 years had worse survival outcomes at 10 years (HR, 1.56; 95% CI, 1.09-2.22) and had a significantly higher risk of death from breast cancer (HR, 1.67; 95% CI, 1.16-2.40; J Bone Oncol. 2018 Sep 27. doi: 10.1016/j.jbo.2018.09.008).
 

Trying to reconcile disparate findings

Those findings left his group with a dilemma, said Dr. Coleman. “Do we start again and run trials, and wait another 10 years, or is there a shortcut to [understanding] what’s going on?” he asked.

In a meta-analysis of all trials from the Early Breast Cancer Trialists’ Collaborative Group in 2015 examining adjuvant bisphosphonate treatment and placebo in patients with early-stage breast cancer, intent-to-treat analyses did not show significant benefit after therapy, but postmenopausal women (11,767 women in 36 trials) saw a clear benefit in all recurrence (rate ratio, 0.86; 95% CI, 0.78-0.94), bone recurrence (RR, 0.72; 95% CI, 0.60-0.86), and breast cancer–related mortality (RR, 0.82; 95% CI, 0.73-0.93; Lancet. 2015 Jul 23. doi: 10.1016/S0140-6736[15]60908-4). The effect seemed to be similar, regardless of bisphosphonate type, with other results seen across trials that used clodronate, zoledronic acid, pamidronate, or ibandronate.

“Although those outcome differences might look quite small for a common disease, that’s a really big effect. Reducing one-sixth of breast cancer deaths at 10 years is the equivalent of saving 10,000 lives across the [European Union], and about half that in the United States,” said Dr. Coleman, noting that guidelines in North America from the American Society of Clinical Oncology and the European Society for Medical Oncology now support adjuvant bisphosphonates in postmenopausal patients with breast cancer.

However, bisphosphonates’ effect on breast cancer does not extend to other cancers, such as non–small cell lung cancer or prostate cancer. In other absorption inhibitors such as denosumab, there also seems to be no benefit for patients with breast cancer, including in postmenopausal patient subgroups, said Dr. Coleman. “In my view, osteoclast inhibition is only part of the story,” he noted.

In the AZURE trial, secondary outcomes examined how the transcription factor MAF interacted with menopausal status and treatment with zoledronic acid. The 79% of patients with tumors that were negative for MAF fluorescence in situ hybridization had improved overall survival (0.69; 95% CI, 0.50-0.94), regardless of menopause status (J Bone Oncol. 2018. doi: 10.1016/j.jbo.2018.09.008). “There’s probably a need to merge the treatment: in this case, the bisphosphonate, the biology of the cancer, and the environment the cancer finds itself in,” noted Dr. Coleman.

“From the cancer perspective, bisphosphonates have transformed the experience for many of our patients with advanced disease, and now we’re working to see great improvements, at least in common diseases such as postmenopausal breast cancer,” he concluded.

Dr. Coleman reports being a paid employee of prIME Oncology (until March 2019); is a consultant for Amgen, Astellas, Boehringer Ingelheim, Scandell, and Biocon; is on the speakers bureau for Amgen and Eisai; holds intellectual property rights for a biomarker being developed by Inbiomotion; and is on the scientific advisory board for Inbiomotion.

LAS VEGAS – The way Neal Bhatia, MD, sees it, there is no such thing as a classical presentation of onychomycosis.

Doug Brunk/MDedge News

“This is where proving your diagnosis is half the battle, even though we are sometimes using empiric therapy in suspected cases,” he said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar. “Prove the diagnosis and get the extra tests necessary.”

According to Dr. Bhatia, director of clinical dermatology research at San Diego-based Therapeutics Clinical Research, tinea unguium, tinea corporis, tinea cruris, and tinea pedis account for more than half of all visits for dermatophytosis. With onychomycosis, the ultimate treatment goal from the standpoint of clinicians is no more fungus, he noted, while the desired endpoint from the standpoint of some patients is normal-looking nails.

“Endpoint failures in a research trial are not the same as what we tell patients in the clinic,” Dr. Bhatia said. “If you have a patient using something topical for 52 weeks and they see two-thirds of their nail improve, you’re not going to say, ‘Stop; you’re a failure now.’ You tell them, ‘Keep going and we’ll keep watching.’ But in the research world, it’s very different when you look at all of the different endpoints that have to be met at the finish line. It’s very important to measure success based on what that patient’s experiencing.”

According to Dr. Bhatia, diagnosing onychomycosis by visual assessment has a sensitivity of 77% and a specificity of 47%, while KOH has a sensitivity between 67% and 93% and specificity between 38% and 78%. PCR, meanwhile, “is quick, but it’s expensive and it has a high false-positive rate. So, in those difficult patients who aren’t responding [to treatment], maybe we can’t just trust our eyes alone [to make a diagnosis].”

Tests such as a KOH stain have low sensitivity, with high costs of more sensitive tests such as the periodic acid–Schiff (PAS) stain. In a recent study, researchers conducted a retrospective cohort analysis of 600 patients with toenail clippings sent for PAS stain during January 2000–December 2013 (J Am Acad Dermatol. 2015 May; 72(5):AB116). They reviewed records to determine which PAS stains were performed to confirm probable clinical diagnosis of onychomycosis.

The researchers found that 30% of toenail clippings were sent for confirmatory PAS staining by dermatologists, compared with 37% by podiatrists and 34% by other clinicians. Of these tests, 75% ordered by dermatologists were positive for fungus, compared with 81% ordered by podiatrists, and 66% ordered by other physicians. “The positive predictive value of clinical suspicion for true onychomycosis was high, and the findings question whether or not a confirmatory test is really necessary,” Dr. Bhatia said.

Preventative strategies to control recurrence of onychomycosis include using maintenance regimens of the recommended antifungal agent, discarding old shoes, alternating wearing different pairs of shoes, periodically disinfecting shoes, washing feet regularly, and alerting the physician to the first sign of infection.

In an effort to investigate strategies to minimize recurrence of onychomycosis, Dr. Bhatia and colleagues evaluated 73 patients over the course of 7 years who were taking either terbinafine or itraconazole (J Drugs Dermatol. 2016;15[3]:279-82). Thirty-six months later, the overall mean recurrence rate among patients was 14%. Prognostic factors influencing recurrence included patient’s family history; lifestyle; underlying physiology (presence of a very thick nail, extensive involvement of the entire nail unit, lateral nail disease and yellow spikes); physical trauma, especially in the elderly; concomitant disease, such as peripheral artery disease and/or diabetes; immunocompromised or immunosuppressed patients, and the presence of tinea pedis.

Based on their analysis, they recommended the following strategies to prevent or limit recurrence: prophylactic use of a topical antifungal twice-weekly for 2-3 years; periodic application of a topical antifungal to plantar surface and/or interdigital spaces; treatment of any coexisting tinea pedis; treating immediate family members; footwear and sock decontamination with antifungal powder; ultraviolet light or ozone; avoidance of activities known to risk spread of disease, such as communal swimming pools.

Dr. Bhatia concluded his presentation by noting that the ideal treatment for onychomycosis would not pose a systemic risk to the liver, heart, or other organs; would not require monitoring of labs; would not require debridement; and would not interact with other drugs. It would also penetrate the nail plate – especially the diseased nail – and would be quick drying.

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

Dr. Bhatia disclosed having affiliations with Actavis, Allergan, Anacor, Aqua, Bayer, Biofrontera, BiopharmX, Cipher, Dermira, Dusa, Exeltis, Ferndale, Foamix, Galderma, Intraderm, ISDIN, LaRoche-Posay, Leo, Novan, Novartis, PharmaDerm, Promius, Regeneron, Sanofi, Sun Pharma, and Valeant.

[email protected]

LAS VEGAS – The way Neal Bhatia, MD, sees it, there is no such thing as a classical presentation of onychomycosis.

Doug Brunk/MDedge News

“This is where proving your diagnosis is half the battle, even though we are sometimes using empiric therapy in suspected cases,” he said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar. “Prove the diagnosis and get the extra tests necessary.”

According to Dr. Bhatia, director of clinical dermatology research at San Diego-based Therapeutics Clinical Research, tinea unguium, tinea corporis, tinea cruris, and tinea pedis account for more than half of all visits for dermatophytosis. With onychomycosis, the ultimate treatment goal from the standpoint of clinicians is no more fungus, he noted, while the desired endpoint from the standpoint of some patients is normal-looking nails.

“Endpoint failures in a research trial are not the same as what we tell patients in the clinic,” Dr. Bhatia said. “If you have a patient using something topical for 52 weeks and they see two-thirds of their nail improve, you’re not going to say, ‘Stop; you’re a failure now.’ You tell them, ‘Keep going and we’ll keep watching.’ But in the research world, it’s very different when you look at all of the different endpoints that have to be met at the finish line. It’s very important to measure success based on what that patient’s experiencing.”

According to Dr. Bhatia, diagnosing onychomycosis by visual assessment has a sensitivity of 77% and a specificity of 47%, while KOH has a sensitivity between 67% and 93% and specificity between 38% and 78%. PCR, meanwhile, “is quick, but it’s expensive and it has a high false-positive rate. So, in those difficult patients who aren’t responding [to treatment], maybe we can’t just trust our eyes alone [to make a diagnosis].”

Tests such as a KOH stain have low sensitivity, with high costs of more sensitive tests such as the periodic acid–Schiff (PAS) stain. In a recent study, researchers conducted a retrospective cohort analysis of 600 patients with toenail clippings sent for PAS stain during January 2000–December 2013 (J Am Acad Dermatol. 2015 May; 72(5):AB116). They reviewed records to determine which PAS stains were performed to confirm probable clinical diagnosis of onychomycosis.

The researchers found that 30% of toenail clippings were sent for confirmatory PAS staining by dermatologists, compared with 37% by podiatrists and 34% by other clinicians. Of these tests, 75% ordered by dermatologists were positive for fungus, compared with 81% ordered by podiatrists, and 66% ordered by other physicians. “The positive predictive value of clinical suspicion for true onychomycosis was high, and the findings question whether or not a confirmatory test is really necessary,” Dr. Bhatia said.

Preventative strategies to control recurrence of onychomycosis include using maintenance regimens of the recommended antifungal agent, discarding old shoes, alternating wearing different pairs of shoes, periodically disinfecting shoes, washing feet regularly, and alerting the physician to the first sign of infection.

In an effort to investigate strategies to minimize recurrence of onychomycosis, Dr. Bhatia and colleagues evaluated 73 patients over the course of 7 years who were taking either terbinafine or itraconazole (J Drugs Dermatol. 2016;15[3]:279-82). Thirty-six months later, the overall mean recurrence rate among patients was 14%. Prognostic factors influencing recurrence included patient’s family history; lifestyle; underlying physiology (presence of a very thick nail, extensive involvement of the entire nail unit, lateral nail disease and yellow spikes); physical trauma, especially in the elderly; concomitant disease, such as peripheral artery disease and/or diabetes; immunocompromised or immunosuppressed patients, and the presence of tinea pedis.

Based on their analysis, they recommended the following strategies to prevent or limit recurrence: prophylactic use of a topical antifungal twice-weekly for 2-3 years; periodic application of a topical antifungal to plantar surface and/or interdigital spaces; treatment of any coexisting tinea pedis; treating immediate family members; footwear and sock decontamination with antifungal powder; ultraviolet light or ozone; avoidance of activities known to risk spread of disease, such as communal swimming pools.

Dr. Bhatia concluded his presentation by noting that the ideal treatment for onychomycosis would not pose a systemic risk to the liver, heart, or other organs; would not require monitoring of labs; would not require debridement; and would not interact with other drugs. It would also penetrate the nail plate – especially the diseased nail – and would be quick drying.

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

Dr. Bhatia disclosed having affiliations with Actavis, Allergan, Anacor, Aqua, Bayer, Biofrontera, BiopharmX, Cipher, Dermira, Dusa, Exeltis, Ferndale, Foamix, Galderma, Intraderm, ISDIN, LaRoche-Posay, Leo, Novan, Novartis, PharmaDerm, Promius, Regeneron, Sanofi, Sun Pharma, and Valeant.

[email protected]

LAS VEGAS – The way Neal Bhatia, MD, sees it, there is no such thing as a classical presentation of onychomycosis.

Doug Brunk/MDedge News

“This is where proving your diagnosis is half the battle, even though we are sometimes using empiric therapy in suspected cases,” he said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar. “Prove the diagnosis and get the extra tests necessary.”

According to Dr. Bhatia, director of clinical dermatology research at San Diego-based Therapeutics Clinical Research, tinea unguium, tinea corporis, tinea cruris, and tinea pedis account for more than half of all visits for dermatophytosis. With onychomycosis, the ultimate treatment goal from the standpoint of clinicians is no more fungus, he noted, while the desired endpoint from the standpoint of some patients is normal-looking nails.

“Endpoint failures in a research trial are not the same as what we tell patients in the clinic,” Dr. Bhatia said. “If you have a patient using something topical for 52 weeks and they see two-thirds of their nail improve, you’re not going to say, ‘Stop; you’re a failure now.’ You tell them, ‘Keep going and we’ll keep watching.’ But in the research world, it’s very different when you look at all of the different endpoints that have to be met at the finish line. It’s very important to measure success based on what that patient’s experiencing.”

According to Dr. Bhatia, diagnosing onychomycosis by visual assessment has a sensitivity of 77% and a specificity of 47%, while KOH has a sensitivity between 67% and 93% and specificity between 38% and 78%. PCR, meanwhile, “is quick, but it’s expensive and it has a high false-positive rate. So, in those difficult patients who aren’t responding [to treatment], maybe we can’t just trust our eyes alone [to make a diagnosis].”

Tests such as a KOH stain have low sensitivity, with high costs of more sensitive tests such as the periodic acid–Schiff (PAS) stain. In a recent study, researchers conducted a retrospective cohort analysis of 600 patients with toenail clippings sent for PAS stain during January 2000–December 2013 (J Am Acad Dermatol. 2015 May; 72(5):AB116). They reviewed records to determine which PAS stains were performed to confirm probable clinical diagnosis of onychomycosis.

The researchers found that 30% of toenail clippings were sent for confirmatory PAS staining by dermatologists, compared with 37% by podiatrists and 34% by other clinicians. Of these tests, 75% ordered by dermatologists were positive for fungus, compared with 81% ordered by podiatrists, and 66% ordered by other physicians. “The positive predictive value of clinical suspicion for true onychomycosis was high, and the findings question whether or not a confirmatory test is really necessary,” Dr. Bhatia said.

Preventative strategies to control recurrence of onychomycosis include using maintenance regimens of the recommended antifungal agent, discarding old shoes, alternating wearing different pairs of shoes, periodically disinfecting shoes, washing feet regularly, and alerting the physician to the first sign of infection.

In an effort to investigate strategies to minimize recurrence of onychomycosis, Dr. Bhatia and colleagues evaluated 73 patients over the course of 7 years who were taking either terbinafine or itraconazole (J Drugs Dermatol. 2016;15[3]:279-82). Thirty-six months later, the overall mean recurrence rate among patients was 14%. Prognostic factors influencing recurrence included patient’s family history; lifestyle; underlying physiology (presence of a very thick nail, extensive involvement of the entire nail unit, lateral nail disease and yellow spikes); physical trauma, especially in the elderly; concomitant disease, such as peripheral artery disease and/or diabetes; immunocompromised or immunosuppressed patients, and the presence of tinea pedis.

Based on their analysis, they recommended the following strategies to prevent or limit recurrence: prophylactic use of a topical antifungal twice-weekly for 2-3 years; periodic application of a topical antifungal to plantar surface and/or interdigital spaces; treatment of any coexisting tinea pedis; treating immediate family members; footwear and sock decontamination with antifungal powder; ultraviolet light or ozone; avoidance of activities known to risk spread of disease, such as communal swimming pools.

Dr. Bhatia concluded his presentation by noting that the ideal treatment for onychomycosis would not pose a systemic risk to the liver, heart, or other organs; would not require monitoring of labs; would not require debridement; and would not interact with other drugs. It would also penetrate the nail plate – especially the diseased nail – and would be quick drying.

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

Dr. Bhatia disclosed having affiliations with Actavis, Allergan, Anacor, Aqua, Bayer, Biofrontera, BiopharmX, Cipher, Dermira, Dusa, Exeltis, Ferndale, Foamix, Galderma, Intraderm, ISDIN, LaRoche-Posay, Leo, Novan, Novartis, PharmaDerm, Promius, Regeneron, Sanofi, Sun Pharma, and Valeant.

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The Food and Drug Administration has approved the first treatment for anemia in adults with transfusion-dependent beta thalassemia.

Olivier Le Moal/Getty Images

Luspatercept-aamt (Reblozyl) is an erythroid maturation agent that reduced the transfusion burden for patients with beta thalassemia in the BELIEVE trial of 336 patients. In total, 21% of patients who received luspatercept-aamt achieved at least a 33% reduction in red blood cell transfusions, compared with 4.5% of patients who received placebo, according to the FDA.

Common side effects associated with luspatercept-aamt were headache, bone pain, arthralgia, fatigue, cough, abdominal pain, diarrhea, and dizziness. Patients taking the agent should be monitored for thrombosis, the FDA advised.

Celgene, which makes luspatercept-aamt, said the agent would be available about 1 week following the FDA approval.

The FDA is also evaluating luspatercept-aamt as an anemia treatment in adults with very-low– to intermediate-risk myelodysplastic syndromes who have ring sideroblasts and require red blood cell transfusions. The agency is expected to take action on that application in April 2020.

[email protected]

The Food and Drug Administration has approved the first treatment for anemia in adults with transfusion-dependent beta thalassemia.

Olivier Le Moal/Getty Images

Luspatercept-aamt (Reblozyl) is an erythroid maturation agent that reduced the transfusion burden for patients with beta thalassemia in the BELIEVE trial of 336 patients. In total, 21% of patients who received luspatercept-aamt achieved at least a 33% reduction in red blood cell transfusions, compared with 4.5% of patients who received placebo, according to the FDA.

Common side effects associated with luspatercept-aamt were headache, bone pain, arthralgia, fatigue, cough, abdominal pain, diarrhea, and dizziness. Patients taking the agent should be monitored for thrombosis, the FDA advised.

Celgene, which makes luspatercept-aamt, said the agent would be available about 1 week following the FDA approval.

The FDA is also evaluating luspatercept-aamt as an anemia treatment in adults with very-low– to intermediate-risk myelodysplastic syndromes who have ring sideroblasts and require red blood cell transfusions. The agency is expected to take action on that application in April 2020.

[email protected]

The Food and Drug Administration has approved the first treatment for anemia in adults with transfusion-dependent beta thalassemia.

Olivier Le Moal/Getty Images

Luspatercept-aamt (Reblozyl) is an erythroid maturation agent that reduced the transfusion burden for patients with beta thalassemia in the BELIEVE trial of 336 patients. In total, 21% of patients who received luspatercept-aamt achieved at least a 33% reduction in red blood cell transfusions, compared with 4.5% of patients who received placebo, according to the FDA.

Common side effects associated with luspatercept-aamt were headache, bone pain, arthralgia, fatigue, cough, abdominal pain, diarrhea, and dizziness. Patients taking the agent should be monitored for thrombosis, the FDA advised.

Celgene, which makes luspatercept-aamt, said the agent would be available about 1 week following the FDA approval.

The FDA is also evaluating luspatercept-aamt as an anemia treatment in adults with very-low– to intermediate-risk myelodysplastic syndromes who have ring sideroblasts and require red blood cell transfusions. The agency is expected to take action on that application in April 2020.

[email protected]