Co-occurrence of Steatocystoma Multiplex, Eruptive Vellus Hair Cysts, and Trichofolliculomas

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Co-occurrence of Steatocystoma Multiplex, Eruptive Vellus Hair Cysts, and Trichofolliculomas

An association between steatocystoma multiplex (SCM) and eruptive vellus hair cysts (EVHCs) has been recognized. They are related conditions representing nevoid malformations of the pilosebaceous junctions1-10 that have similar clinical features but distinctive histologic features. Both conditions most commonly involve the anterior aspect of the chest. Six cases of a rare facial variant of SCM have been reported,11-16 3 involving lesions limited to the forehead.13-15 Two patients with a rare facial variant of EVHC also have been reported.17 The development of separate lesions of SCM and EVHC on the trunk can uncommonly occur.5,6,10 One case of SCM and EVHC on the forehead has been described.3 Other types of benign follicular neoplasms simultaneously developing in association with SCM or EVHC also are rare. The simultaneous occurrence of multiple trichoblastomas, trichoepitheliomas, and SCM on the face and trunk has been reported in 1 case.18 Milia, SCM, and EVHC on the face and trunk have been reported in 1 family.4 A report of facial steatocystoma associated with a pilar cyst and bilateral preauricular sinus also has occurred in 1 patient.19 Here, we report the simultaneous occurrence of SCM, EVHC, and trichofolliculomas localized to the forehead.

Case Report

A 37-year-old man had an increasing number of flesh-colored to yellow papules on the forehead that had been present since puberty. Although the lesions were asymptomatic, some had recently become tender, which led him to seek medical care. There was no history of trauma, burns, irradiation, or application of topical agents to the area or use of eyeglasses or goggles. The patient’s father had similar lesions limited to the forehead, which developed during adolescence.

On evaluation at our clinic, skin examination revealed 16 discrete, 0.3- to 1-cm, flesh-colored, yellow to blue, mobile, smooth papules, as well as flesh-colored papules with a central black punctum, on the forehead (Figure 1). Similar lesions were not present on the rest of the face; around the ears; or on the scalp, neck, chest, back, abdomen, genitalia, buttocks, palms, soles, axillae, arms, or legs. There were no nail abnormalities.

Figure 1. Multiple 0.3- to 1-cm, flesh-colored, yellow to blue, smooth, mobile papules on the forehead (A and B). A 3-mm, flesh-colored papule with a central black punctum on the center of the forehead (C).

Multiple 3-, 4-, and 6-mm punch and excisional biopsies were performed to remove all 16 lesions on the forehead. Histologic examination revealed a collapsed cystic structure in the mid dermis in 10 lesions. The cysts were lined with a squamous epithelium without a granular layer but with an eosinophilic corrugated lining, and the cyst cavity contained scant homogeneous eosinophilic secretion. Mature sebaceous glands were adjacent to the outer portion of the cyst wall. These histologic findings were consistent with SCM (Figure 2).

Figure 2. Photomicrograph of a steatocystoma multiplex lesion demonstrated a collapsed cystic space with parallel infoldings of the cyst wall. The cyst wall was composed of a squamous epithelium without a granular layer but with an eosinophilic corrugated lining. The cyst cavity contained scant homogeneous eosinophilic secretion. Mature sebaceous lobules emanated from the cyst wall (H&E, original magnification ×10).

In 3 lesions, histologic examination revealed a cystic structure lined by a few layers of stratified squamous epithelium in the mid dermis. The cyst cavity contained numerous small vellus hairs and laminated keratin. These histologic findings were consistent with EVHC (Figure 3).

Figure 3. Photomicrograph of eruptive vellus hair cysts demonstrated a small cystic structure lined by squamous epithelium with a granular layer in the mid dermis. The cyst cavity contained numerous small vellus hairs and laminated keratin (H&E, original magnification ×10).

In the other 3 lesions, histologic examination revealed a dilated central cystic cavity filled with laminated keratin in the mid dermis. Multiple small follicles arose from the cysts and showed differentiation toward germinative epithelium. The surrounding stroma was fibrotic and contained a patchy lymphocytic infiltrate. These histologic findings were consistent with trichofolliculomas (Figure 4).

Figure 4. Photomicrograph of a trichofolliculoma demonstrated a central dilated primary follicle that was contiguous with the surface epidermis and contained laminated keratin. Multiple small secondary follicles arose from the primary follicle. These secondary follicles showed differentiation toward germinative epithelium and hair bulb and papilla formation. The stroma was fibrotic (H&E, original magnification ×10).
 

 

Comment

Characteristics of SCM
Steatocystoma multiplex is an uncommon condition characterized by the formation of asymptomatic, 0.2- to 2-cm, yellow to flesh-colored, soft, mobile papules or nodules on the trunk, extremities, axillae, genitalia, and/or chest. The lesions contain a clear or opaque, oily, milky or yellow, odorless fluid and most commonly are located on the anterior aspect of the chest. The face is not a commonly involved site in this condition. Six cases of a rare facial variant of SCM have been reported,11-16 with lesions limited to the forehead in 3 cases.13-15

In 1937, Mount20 credited Bozellini for describing the first case, though 3 cases reported in the late 1800s probably were SCM.21 In 1899, Pringle22 coined the term steatocystoma multiplex for this condition. It can be sporadic or have an autosomal-dominant inheritance pattern. Steatocystoma multiplex can occur at any age, though lesions develop most frequently in adolescence or young adulthood. There is no sex predilection.

Steatocystoma multiplex with pachyonychia congenita has been reported in a familial case.23 Other findings reported in patients with SCM include ichthyosis, koilonychia, acrokeratosis verruciformis of Hopf and hypertrophic lichen planus, hidradenitis suppurativa, hypotrichosis, multiple keratoacanthomas, and rheumatoid arthritis.12,24-26

Steatocystoma multiplex is a cyst lined by stratified squamous epithelium without a granular layer but with a thick eosinophilic cuticle. Mature sebaceous lobules are closely associated with the cyst wall. Steatocystoma multiplex arises from the sebaceous duct because the lining of the lumen is composed of undulating eosinophilic cuticle.

Characteristics of EVHCs
Eruptive vellus hair cysts, which were first described by Esterly et al,27 can occur at any age but develop most frequently in adolescents or young adults. Sometimes the lesions are congenital or appear in childhood. There is no sex predilection. They can be sporadic or have an autosomal-dominant inheritance pattern.

Eruptive vellus hair cysts are asymptomatic, 1- to 2-mm, smooth, crusted, or umbilicated papules on the chest or arms and legs. Eruptive vellus hair cysts most commonly involve the anterior aspect of the chest. The lesions are flesh-colored to yellow, though they have a slate gray color in darker-skinned individuals. A rare facial variant has been reported in 2 patients of Asian descent.17

Eruptive vellus hair cysts are small cystic structures lined by a stratified squamous epithelium with a granular layer. The cyst cavity contains numerous small vellus hair shafts and laminated keratin. Eruptive vellus hair cysts originate from the infundibulum or less frequently the isthmus or infundibular-isthmic junction of the hair follicle.

Characteristics of Trichofolliculomas
Trichofolliculomas are solitary, 3- to 5-mm, flesh-colored papules that occur on the face. They are highly differentiated, benign, neoplastic proliferations of an actively trichogenic epithelium, with structural components reflecting all portions of the pilosebaceous unit. Trichofolliculomas consist of a central dilated primary follicle contiguous with the surface epidermis embedded in a fibrous stroma. Multiple small secondary follicles with varying degrees of follicular differentiation arise from the primary follicle.

Co-occurrence of Lesions
An association between SCM and EVHC has been recognized.5-10 Steatocystoma multiplex and EVHC have similar clinical features but distinctive histologic features. They also have a similar age of onset, location/appearance of lesions, and mode of inheritance. Steatocystoma multiplex and EVHC can be distinguished by immunohistochemical techniques: SCM shows expression of keratin 10 and keratin 17, whereas EVHCs express only keratin 17.28

Steatocystoma multiplex and EVHC have only rarely been reported to occur together on the trunk. One case of SCM and EVHC occurring on the forehead has been described.3 Other types of benign follicular neoplasms simultaneously developing in association with SCM or EVHC also are rare. Milia, SCM, and EVHC on the face and trunk have been reported in 1 family,4 and facial steatocystoma associated with a pilar cyst and bilateral preauricular sinus was reported in 1 patient.19 Although trichofolliculomas have not been reported to occur with SCM or EVHC, 2 related follicular neoplasms—trichoepitheliomas and trichoblastomas—have been reported to occur in association with SCM on the face and chest and around the ears in 1 case.18

Differential Diagnosis
The clinical differential diagnosis includes multiple epidermoid cysts, dermoid cysts, Gardner syndrome, sebaceous adenomas, Muir-Torre syndrome, syringomas, milia, leiomyomas, lipomas, acneiform folliculitis, multiple familial and nonfamilial trichoepitheliomas, cylindromas, and angiofibromas.3,29

Conclusion

Our patient represents a rare case of simultaneous occurrence of SCM, EVHC, and trichofolliculomas localized to the forehead. The patient had multiple neoplasms involving differentiation toward various regions of the pilosebaceous unit. This case gives further support to the hypothesis that these benign follicular neoplasms are closely related but are distinct conditions within the spectrum of the same disease process. They represent nevoid malformations of the pilosebaceous unit that can be sporadic or inherited in an autosomal-dominant pattern. Pure types of these lesions may represent one end of the spectrum, but in some patients, there are overlapping features or hybrids of each condition. Several biopsies from patients with multiple lesions should be performed to establish an accurate diagnosis.

References
  1. Cho S, Chang SE, Choi JH, et al. Clinical and histologic features of 64 cases of steatocystoma multiplex. J Dermatol. 2002;29:152-156.
  2. Ogawa Y, Nogita T, Kawashima M. The coexistence of eruptive vellus hair cysts and steatocystoma multiplex. J Dermatol. 1992;19:570-571.
  3. Sanchez Yus E, Requena L. Eruptive vellus hair cyst and steatocystoma multiplex. Am J Dermatopathol. 1990;12:536-537.
  4. Patrizi A, Neri I, Guerrini V, et al. Persistent milia, steatocystoma multiplex and eruptive vellus hair cysts: variable expression of multiple pilosebaceous cysts within an affected family. Dermatology. 1998;196:392-396.
  5. Ohtake N, Kubota Y, Takayama O, et al. Relationship between steatocystoma multiplex and eruptive vellus hair cysts. J Am Acad Dermatol. 1992;26(5, pt 2):876-878.
  6. Kiene P, Hauschild A, Christophers E. Eruptive vellus hair cysts and steatocystoma multiplex: variants of one entity? Br J Dermatol. 1996;134:365-367.
  7. Hurlimann AF, Panizzon RG, Burg G. Eruptive vellus hair cyst and steatocystoma multiplex: hybrid cysts. Dermatology. 1996;192:64-66.
  8. Sexton M, Murdock DK. Eruptive vellus hair cysts: a follicular cyst of the sebaceous duct (sometimes). Am J Dermatopathol. 1989;11:364-368.
  9. Sanchez-Yus E, Aguilar-Martinez A, Cristobal-Gil MC, et al. Eruptive vellus hair cyst and steatocystoma multiplex: two related conditions? J Cutan Pathol. 1988;15:40-42.
  10. Ahn SK, Chung J, Lee WS, et al. Hybrid cysts showing alternate combination of eruptive vellus hair cyst, steatocystoma multiplex, and epidermoid cyst, and an association among the three conditions. Am J Dermatopathol. 1996;18:645-649.
  11. Ahn SK, Hwang SM, Lee SH, et al. Steatocystoma multiplex localized only in the face. Int J Dermatol. 1997;36:372-373.
  12. Cole LA. Steatocystoma multiplex. Arch Dermatol. 1976;112:1437-1439.
  13. Hansen KK, Troy JL, Fairley JA. Multiple papules of the scalp and forehead. steatocystoma multiplex (facial papular variant). Arch Dermatol. 1995;131:835-838.
  14. Nishimura M, Kohda H, Urabe A. Steatocystoma multiplex: a facial popular variant. Arch Dermatol. 1986;122:205-207.
  15. Requena L, Martin L, Renedo G, et al. A facial variant of steatocystoma multiplex. Cutis. 1993;51:449-452.
  16. Holmes R, Black MM. Steatocystoma multiplex with unusually prominent cysts on the face. Br J Dermatol. 1980;102:711-713.
  17. Kumakiri M, Takashima I, Iju M, et al. Eruptive vellus hair cysts: a facial variant. J Am Acad Dermatol. 1982;7:461-467.
  18. Gianotti R, Cavicchini S, Alessi E. Simultaneous occurrence of multiple trichoblastomas and steatocystoma multiplex. Am J Dermatopathol. 1997;19:294-298.
  19. Sardana K, Sharma RC, Jain A, et al. Facial steatocystoma multiplex associated with pilar cyst and bilateral preauricular sinus. J Dermatol. 2002;29:157-159.
  20. Mount LB. Steatocystoma multiplex. Arch Dermatol Syphilol. 1937;36:31-39.
  21. Dubreuilh W, Auche B. Kystes grassieux sudoripares. Arch Clin de Bordeaux. 1896;5:387-391.
  22. Pringle JJ. A case of peculiar multiple sebaceous cysts (steatocystoma multiplex). Br J Dermatol. 1899;11:381-88.
  23. Vineyard WR, Scott RA. Steatocystoma multiplex with pachyonychia congenital: eight cases in four generations. Arch Dermatol. 1961;84:824-827.
  24. Contreras MA, Costello MJ. Steatocystoma multiplex with embryonal hair formation: case presentation and consideration of pathogenesis. AMA Arch Derm. 1957;76:720-725.
  25. Sohn D, Chin TC, Fellner MJ. Multiple keratoacanthomas associated with steatocystoma multiplex and rheumatoid arthritis: a case report. Arch Dermatol. 1980;116:913-915.
  26. Verbov J. Acrokeratosis verruciformis of Hopf with steatocystoma multiplex and hypertrophic lichen planus. Br J Dermatol. 1972;86:91-94.
  27. Esterly NB, Fretzin DF, Pinkus H. Eruptive vellus hair cysts. Arch Dermatol. 1977;113:500-503.
  28. Tomkova H, Fujimoto W, Arata J. Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus hair cysts, and epidermoid and trichilemmal cysts. Am J Dermatopathol. 1997;19:250-253.
  29. Feinstein A, Trau H, Movshovitz M, et al. Steatocystoma multiplex. Cutis. 1983;31:425-427.
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The authors report no conflict of interest.

Correspondence: Alina G. Bridges, DO, Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (bridges.alina@mayo.edu).

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From the Department of Dermatology and the Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.

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Related Articles

An association between steatocystoma multiplex (SCM) and eruptive vellus hair cysts (EVHCs) has been recognized. They are related conditions representing nevoid malformations of the pilosebaceous junctions1-10 that have similar clinical features but distinctive histologic features. Both conditions most commonly involve the anterior aspect of the chest. Six cases of a rare facial variant of SCM have been reported,11-16 3 involving lesions limited to the forehead.13-15 Two patients with a rare facial variant of EVHC also have been reported.17 The development of separate lesions of SCM and EVHC on the trunk can uncommonly occur.5,6,10 One case of SCM and EVHC on the forehead has been described.3 Other types of benign follicular neoplasms simultaneously developing in association with SCM or EVHC also are rare. The simultaneous occurrence of multiple trichoblastomas, trichoepitheliomas, and SCM on the face and trunk has been reported in 1 case.18 Milia, SCM, and EVHC on the face and trunk have been reported in 1 family.4 A report of facial steatocystoma associated with a pilar cyst and bilateral preauricular sinus also has occurred in 1 patient.19 Here, we report the simultaneous occurrence of SCM, EVHC, and trichofolliculomas localized to the forehead.

Case Report

A 37-year-old man had an increasing number of flesh-colored to yellow papules on the forehead that had been present since puberty. Although the lesions were asymptomatic, some had recently become tender, which led him to seek medical care. There was no history of trauma, burns, irradiation, or application of topical agents to the area or use of eyeglasses or goggles. The patient’s father had similar lesions limited to the forehead, which developed during adolescence.

On evaluation at our clinic, skin examination revealed 16 discrete, 0.3- to 1-cm, flesh-colored, yellow to blue, mobile, smooth papules, as well as flesh-colored papules with a central black punctum, on the forehead (Figure 1). Similar lesions were not present on the rest of the face; around the ears; or on the scalp, neck, chest, back, abdomen, genitalia, buttocks, palms, soles, axillae, arms, or legs. There were no nail abnormalities.

Figure 1. Multiple 0.3- to 1-cm, flesh-colored, yellow to blue, smooth, mobile papules on the forehead (A and B). A 3-mm, flesh-colored papule with a central black punctum on the center of the forehead (C).

Multiple 3-, 4-, and 6-mm punch and excisional biopsies were performed to remove all 16 lesions on the forehead. Histologic examination revealed a collapsed cystic structure in the mid dermis in 10 lesions. The cysts were lined with a squamous epithelium without a granular layer but with an eosinophilic corrugated lining, and the cyst cavity contained scant homogeneous eosinophilic secretion. Mature sebaceous glands were adjacent to the outer portion of the cyst wall. These histologic findings were consistent with SCM (Figure 2).

Figure 2. Photomicrograph of a steatocystoma multiplex lesion demonstrated a collapsed cystic space with parallel infoldings of the cyst wall. The cyst wall was composed of a squamous epithelium without a granular layer but with an eosinophilic corrugated lining. The cyst cavity contained scant homogeneous eosinophilic secretion. Mature sebaceous lobules emanated from the cyst wall (H&E, original magnification ×10).

In 3 lesions, histologic examination revealed a cystic structure lined by a few layers of stratified squamous epithelium in the mid dermis. The cyst cavity contained numerous small vellus hairs and laminated keratin. These histologic findings were consistent with EVHC (Figure 3).

Figure 3. Photomicrograph of eruptive vellus hair cysts demonstrated a small cystic structure lined by squamous epithelium with a granular layer in the mid dermis. The cyst cavity contained numerous small vellus hairs and laminated keratin (H&E, original magnification ×10).

In the other 3 lesions, histologic examination revealed a dilated central cystic cavity filled with laminated keratin in the mid dermis. Multiple small follicles arose from the cysts and showed differentiation toward germinative epithelium. The surrounding stroma was fibrotic and contained a patchy lymphocytic infiltrate. These histologic findings were consistent with trichofolliculomas (Figure 4).

Figure 4. Photomicrograph of a trichofolliculoma demonstrated a central dilated primary follicle that was contiguous with the surface epidermis and contained laminated keratin. Multiple small secondary follicles arose from the primary follicle. These secondary follicles showed differentiation toward germinative epithelium and hair bulb and papilla formation. The stroma was fibrotic (H&E, original magnification ×10).
 

 

Comment

Characteristics of SCM
Steatocystoma multiplex is an uncommon condition characterized by the formation of asymptomatic, 0.2- to 2-cm, yellow to flesh-colored, soft, mobile papules or nodules on the trunk, extremities, axillae, genitalia, and/or chest. The lesions contain a clear or opaque, oily, milky or yellow, odorless fluid and most commonly are located on the anterior aspect of the chest. The face is not a commonly involved site in this condition. Six cases of a rare facial variant of SCM have been reported,11-16 with lesions limited to the forehead in 3 cases.13-15

In 1937, Mount20 credited Bozellini for describing the first case, though 3 cases reported in the late 1800s probably were SCM.21 In 1899, Pringle22 coined the term steatocystoma multiplex for this condition. It can be sporadic or have an autosomal-dominant inheritance pattern. Steatocystoma multiplex can occur at any age, though lesions develop most frequently in adolescence or young adulthood. There is no sex predilection.

Steatocystoma multiplex with pachyonychia congenita has been reported in a familial case.23 Other findings reported in patients with SCM include ichthyosis, koilonychia, acrokeratosis verruciformis of Hopf and hypertrophic lichen planus, hidradenitis suppurativa, hypotrichosis, multiple keratoacanthomas, and rheumatoid arthritis.12,24-26

Steatocystoma multiplex is a cyst lined by stratified squamous epithelium without a granular layer but with a thick eosinophilic cuticle. Mature sebaceous lobules are closely associated with the cyst wall. Steatocystoma multiplex arises from the sebaceous duct because the lining of the lumen is composed of undulating eosinophilic cuticle.

Characteristics of EVHCs
Eruptive vellus hair cysts, which were first described by Esterly et al,27 can occur at any age but develop most frequently in adolescents or young adults. Sometimes the lesions are congenital or appear in childhood. There is no sex predilection. They can be sporadic or have an autosomal-dominant inheritance pattern.

Eruptive vellus hair cysts are asymptomatic, 1- to 2-mm, smooth, crusted, or umbilicated papules on the chest or arms and legs. Eruptive vellus hair cysts most commonly involve the anterior aspect of the chest. The lesions are flesh-colored to yellow, though they have a slate gray color in darker-skinned individuals. A rare facial variant has been reported in 2 patients of Asian descent.17

Eruptive vellus hair cysts are small cystic structures lined by a stratified squamous epithelium with a granular layer. The cyst cavity contains numerous small vellus hair shafts and laminated keratin. Eruptive vellus hair cysts originate from the infundibulum or less frequently the isthmus or infundibular-isthmic junction of the hair follicle.

Characteristics of Trichofolliculomas
Trichofolliculomas are solitary, 3- to 5-mm, flesh-colored papules that occur on the face. They are highly differentiated, benign, neoplastic proliferations of an actively trichogenic epithelium, with structural components reflecting all portions of the pilosebaceous unit. Trichofolliculomas consist of a central dilated primary follicle contiguous with the surface epidermis embedded in a fibrous stroma. Multiple small secondary follicles with varying degrees of follicular differentiation arise from the primary follicle.

Co-occurrence of Lesions
An association between SCM and EVHC has been recognized.5-10 Steatocystoma multiplex and EVHC have similar clinical features but distinctive histologic features. They also have a similar age of onset, location/appearance of lesions, and mode of inheritance. Steatocystoma multiplex and EVHC can be distinguished by immunohistochemical techniques: SCM shows expression of keratin 10 and keratin 17, whereas EVHCs express only keratin 17.28

Steatocystoma multiplex and EVHC have only rarely been reported to occur together on the trunk. One case of SCM and EVHC occurring on the forehead has been described.3 Other types of benign follicular neoplasms simultaneously developing in association with SCM or EVHC also are rare. Milia, SCM, and EVHC on the face and trunk have been reported in 1 family,4 and facial steatocystoma associated with a pilar cyst and bilateral preauricular sinus was reported in 1 patient.19 Although trichofolliculomas have not been reported to occur with SCM or EVHC, 2 related follicular neoplasms—trichoepitheliomas and trichoblastomas—have been reported to occur in association with SCM on the face and chest and around the ears in 1 case.18

Differential Diagnosis
The clinical differential diagnosis includes multiple epidermoid cysts, dermoid cysts, Gardner syndrome, sebaceous adenomas, Muir-Torre syndrome, syringomas, milia, leiomyomas, lipomas, acneiform folliculitis, multiple familial and nonfamilial trichoepitheliomas, cylindromas, and angiofibromas.3,29

Conclusion

Our patient represents a rare case of simultaneous occurrence of SCM, EVHC, and trichofolliculomas localized to the forehead. The patient had multiple neoplasms involving differentiation toward various regions of the pilosebaceous unit. This case gives further support to the hypothesis that these benign follicular neoplasms are closely related but are distinct conditions within the spectrum of the same disease process. They represent nevoid malformations of the pilosebaceous unit that can be sporadic or inherited in an autosomal-dominant pattern. Pure types of these lesions may represent one end of the spectrum, but in some patients, there are overlapping features or hybrids of each condition. Several biopsies from patients with multiple lesions should be performed to establish an accurate diagnosis.

An association between steatocystoma multiplex (SCM) and eruptive vellus hair cysts (EVHCs) has been recognized. They are related conditions representing nevoid malformations of the pilosebaceous junctions1-10 that have similar clinical features but distinctive histologic features. Both conditions most commonly involve the anterior aspect of the chest. Six cases of a rare facial variant of SCM have been reported,11-16 3 involving lesions limited to the forehead.13-15 Two patients with a rare facial variant of EVHC also have been reported.17 The development of separate lesions of SCM and EVHC on the trunk can uncommonly occur.5,6,10 One case of SCM and EVHC on the forehead has been described.3 Other types of benign follicular neoplasms simultaneously developing in association with SCM or EVHC also are rare. The simultaneous occurrence of multiple trichoblastomas, trichoepitheliomas, and SCM on the face and trunk has been reported in 1 case.18 Milia, SCM, and EVHC on the face and trunk have been reported in 1 family.4 A report of facial steatocystoma associated with a pilar cyst and bilateral preauricular sinus also has occurred in 1 patient.19 Here, we report the simultaneous occurrence of SCM, EVHC, and trichofolliculomas localized to the forehead.

Case Report

A 37-year-old man had an increasing number of flesh-colored to yellow papules on the forehead that had been present since puberty. Although the lesions were asymptomatic, some had recently become tender, which led him to seek medical care. There was no history of trauma, burns, irradiation, or application of topical agents to the area or use of eyeglasses or goggles. The patient’s father had similar lesions limited to the forehead, which developed during adolescence.

On evaluation at our clinic, skin examination revealed 16 discrete, 0.3- to 1-cm, flesh-colored, yellow to blue, mobile, smooth papules, as well as flesh-colored papules with a central black punctum, on the forehead (Figure 1). Similar lesions were not present on the rest of the face; around the ears; or on the scalp, neck, chest, back, abdomen, genitalia, buttocks, palms, soles, axillae, arms, or legs. There were no nail abnormalities.

Figure 1. Multiple 0.3- to 1-cm, flesh-colored, yellow to blue, smooth, mobile papules on the forehead (A and B). A 3-mm, flesh-colored papule with a central black punctum on the center of the forehead (C).

Multiple 3-, 4-, and 6-mm punch and excisional biopsies were performed to remove all 16 lesions on the forehead. Histologic examination revealed a collapsed cystic structure in the mid dermis in 10 lesions. The cysts were lined with a squamous epithelium without a granular layer but with an eosinophilic corrugated lining, and the cyst cavity contained scant homogeneous eosinophilic secretion. Mature sebaceous glands were adjacent to the outer portion of the cyst wall. These histologic findings were consistent with SCM (Figure 2).

Figure 2. Photomicrograph of a steatocystoma multiplex lesion demonstrated a collapsed cystic space with parallel infoldings of the cyst wall. The cyst wall was composed of a squamous epithelium without a granular layer but with an eosinophilic corrugated lining. The cyst cavity contained scant homogeneous eosinophilic secretion. Mature sebaceous lobules emanated from the cyst wall (H&E, original magnification ×10).

In 3 lesions, histologic examination revealed a cystic structure lined by a few layers of stratified squamous epithelium in the mid dermis. The cyst cavity contained numerous small vellus hairs and laminated keratin. These histologic findings were consistent with EVHC (Figure 3).

Figure 3. Photomicrograph of eruptive vellus hair cysts demonstrated a small cystic structure lined by squamous epithelium with a granular layer in the mid dermis. The cyst cavity contained numerous small vellus hairs and laminated keratin (H&E, original magnification ×10).

In the other 3 lesions, histologic examination revealed a dilated central cystic cavity filled with laminated keratin in the mid dermis. Multiple small follicles arose from the cysts and showed differentiation toward germinative epithelium. The surrounding stroma was fibrotic and contained a patchy lymphocytic infiltrate. These histologic findings were consistent with trichofolliculomas (Figure 4).

Figure 4. Photomicrograph of a trichofolliculoma demonstrated a central dilated primary follicle that was contiguous with the surface epidermis and contained laminated keratin. Multiple small secondary follicles arose from the primary follicle. These secondary follicles showed differentiation toward germinative epithelium and hair bulb and papilla formation. The stroma was fibrotic (H&E, original magnification ×10).
 

 

Comment

Characteristics of SCM
Steatocystoma multiplex is an uncommon condition characterized by the formation of asymptomatic, 0.2- to 2-cm, yellow to flesh-colored, soft, mobile papules or nodules on the trunk, extremities, axillae, genitalia, and/or chest. The lesions contain a clear or opaque, oily, milky or yellow, odorless fluid and most commonly are located on the anterior aspect of the chest. The face is not a commonly involved site in this condition. Six cases of a rare facial variant of SCM have been reported,11-16 with lesions limited to the forehead in 3 cases.13-15

In 1937, Mount20 credited Bozellini for describing the first case, though 3 cases reported in the late 1800s probably were SCM.21 In 1899, Pringle22 coined the term steatocystoma multiplex for this condition. It can be sporadic or have an autosomal-dominant inheritance pattern. Steatocystoma multiplex can occur at any age, though lesions develop most frequently in adolescence or young adulthood. There is no sex predilection.

Steatocystoma multiplex with pachyonychia congenita has been reported in a familial case.23 Other findings reported in patients with SCM include ichthyosis, koilonychia, acrokeratosis verruciformis of Hopf and hypertrophic lichen planus, hidradenitis suppurativa, hypotrichosis, multiple keratoacanthomas, and rheumatoid arthritis.12,24-26

Steatocystoma multiplex is a cyst lined by stratified squamous epithelium without a granular layer but with a thick eosinophilic cuticle. Mature sebaceous lobules are closely associated with the cyst wall. Steatocystoma multiplex arises from the sebaceous duct because the lining of the lumen is composed of undulating eosinophilic cuticle.

Characteristics of EVHCs
Eruptive vellus hair cysts, which were first described by Esterly et al,27 can occur at any age but develop most frequently in adolescents or young adults. Sometimes the lesions are congenital or appear in childhood. There is no sex predilection. They can be sporadic or have an autosomal-dominant inheritance pattern.

Eruptive vellus hair cysts are asymptomatic, 1- to 2-mm, smooth, crusted, or umbilicated papules on the chest or arms and legs. Eruptive vellus hair cysts most commonly involve the anterior aspect of the chest. The lesions are flesh-colored to yellow, though they have a slate gray color in darker-skinned individuals. A rare facial variant has been reported in 2 patients of Asian descent.17

Eruptive vellus hair cysts are small cystic structures lined by a stratified squamous epithelium with a granular layer. The cyst cavity contains numerous small vellus hair shafts and laminated keratin. Eruptive vellus hair cysts originate from the infundibulum or less frequently the isthmus or infundibular-isthmic junction of the hair follicle.

Characteristics of Trichofolliculomas
Trichofolliculomas are solitary, 3- to 5-mm, flesh-colored papules that occur on the face. They are highly differentiated, benign, neoplastic proliferations of an actively trichogenic epithelium, with structural components reflecting all portions of the pilosebaceous unit. Trichofolliculomas consist of a central dilated primary follicle contiguous with the surface epidermis embedded in a fibrous stroma. Multiple small secondary follicles with varying degrees of follicular differentiation arise from the primary follicle.

Co-occurrence of Lesions
An association between SCM and EVHC has been recognized.5-10 Steatocystoma multiplex and EVHC have similar clinical features but distinctive histologic features. They also have a similar age of onset, location/appearance of lesions, and mode of inheritance. Steatocystoma multiplex and EVHC can be distinguished by immunohistochemical techniques: SCM shows expression of keratin 10 and keratin 17, whereas EVHCs express only keratin 17.28

Steatocystoma multiplex and EVHC have only rarely been reported to occur together on the trunk. One case of SCM and EVHC occurring on the forehead has been described.3 Other types of benign follicular neoplasms simultaneously developing in association with SCM or EVHC also are rare. Milia, SCM, and EVHC on the face and trunk have been reported in 1 family,4 and facial steatocystoma associated with a pilar cyst and bilateral preauricular sinus was reported in 1 patient.19 Although trichofolliculomas have not been reported to occur with SCM or EVHC, 2 related follicular neoplasms—trichoepitheliomas and trichoblastomas—have been reported to occur in association with SCM on the face and chest and around the ears in 1 case.18

Differential Diagnosis
The clinical differential diagnosis includes multiple epidermoid cysts, dermoid cysts, Gardner syndrome, sebaceous adenomas, Muir-Torre syndrome, syringomas, milia, leiomyomas, lipomas, acneiform folliculitis, multiple familial and nonfamilial trichoepitheliomas, cylindromas, and angiofibromas.3,29

Conclusion

Our patient represents a rare case of simultaneous occurrence of SCM, EVHC, and trichofolliculomas localized to the forehead. The patient had multiple neoplasms involving differentiation toward various regions of the pilosebaceous unit. This case gives further support to the hypothesis that these benign follicular neoplasms are closely related but are distinct conditions within the spectrum of the same disease process. They represent nevoid malformations of the pilosebaceous unit that can be sporadic or inherited in an autosomal-dominant pattern. Pure types of these lesions may represent one end of the spectrum, but in some patients, there are overlapping features or hybrids of each condition. Several biopsies from patients with multiple lesions should be performed to establish an accurate diagnosis.

References
  1. Cho S, Chang SE, Choi JH, et al. Clinical and histologic features of 64 cases of steatocystoma multiplex. J Dermatol. 2002;29:152-156.
  2. Ogawa Y, Nogita T, Kawashima M. The coexistence of eruptive vellus hair cysts and steatocystoma multiplex. J Dermatol. 1992;19:570-571.
  3. Sanchez Yus E, Requena L. Eruptive vellus hair cyst and steatocystoma multiplex. Am J Dermatopathol. 1990;12:536-537.
  4. Patrizi A, Neri I, Guerrini V, et al. Persistent milia, steatocystoma multiplex and eruptive vellus hair cysts: variable expression of multiple pilosebaceous cysts within an affected family. Dermatology. 1998;196:392-396.
  5. Ohtake N, Kubota Y, Takayama O, et al. Relationship between steatocystoma multiplex and eruptive vellus hair cysts. J Am Acad Dermatol. 1992;26(5, pt 2):876-878.
  6. Kiene P, Hauschild A, Christophers E. Eruptive vellus hair cysts and steatocystoma multiplex: variants of one entity? Br J Dermatol. 1996;134:365-367.
  7. Hurlimann AF, Panizzon RG, Burg G. Eruptive vellus hair cyst and steatocystoma multiplex: hybrid cysts. Dermatology. 1996;192:64-66.
  8. Sexton M, Murdock DK. Eruptive vellus hair cysts: a follicular cyst of the sebaceous duct (sometimes). Am J Dermatopathol. 1989;11:364-368.
  9. Sanchez-Yus E, Aguilar-Martinez A, Cristobal-Gil MC, et al. Eruptive vellus hair cyst and steatocystoma multiplex: two related conditions? J Cutan Pathol. 1988;15:40-42.
  10. Ahn SK, Chung J, Lee WS, et al. Hybrid cysts showing alternate combination of eruptive vellus hair cyst, steatocystoma multiplex, and epidermoid cyst, and an association among the three conditions. Am J Dermatopathol. 1996;18:645-649.
  11. Ahn SK, Hwang SM, Lee SH, et al. Steatocystoma multiplex localized only in the face. Int J Dermatol. 1997;36:372-373.
  12. Cole LA. Steatocystoma multiplex. Arch Dermatol. 1976;112:1437-1439.
  13. Hansen KK, Troy JL, Fairley JA. Multiple papules of the scalp and forehead. steatocystoma multiplex (facial papular variant). Arch Dermatol. 1995;131:835-838.
  14. Nishimura M, Kohda H, Urabe A. Steatocystoma multiplex: a facial popular variant. Arch Dermatol. 1986;122:205-207.
  15. Requena L, Martin L, Renedo G, et al. A facial variant of steatocystoma multiplex. Cutis. 1993;51:449-452.
  16. Holmes R, Black MM. Steatocystoma multiplex with unusually prominent cysts on the face. Br J Dermatol. 1980;102:711-713.
  17. Kumakiri M, Takashima I, Iju M, et al. Eruptive vellus hair cysts: a facial variant. J Am Acad Dermatol. 1982;7:461-467.
  18. Gianotti R, Cavicchini S, Alessi E. Simultaneous occurrence of multiple trichoblastomas and steatocystoma multiplex. Am J Dermatopathol. 1997;19:294-298.
  19. Sardana K, Sharma RC, Jain A, et al. Facial steatocystoma multiplex associated with pilar cyst and bilateral preauricular sinus. J Dermatol. 2002;29:157-159.
  20. Mount LB. Steatocystoma multiplex. Arch Dermatol Syphilol. 1937;36:31-39.
  21. Dubreuilh W, Auche B. Kystes grassieux sudoripares. Arch Clin de Bordeaux. 1896;5:387-391.
  22. Pringle JJ. A case of peculiar multiple sebaceous cysts (steatocystoma multiplex). Br J Dermatol. 1899;11:381-88.
  23. Vineyard WR, Scott RA. Steatocystoma multiplex with pachyonychia congenital: eight cases in four generations. Arch Dermatol. 1961;84:824-827.
  24. Contreras MA, Costello MJ. Steatocystoma multiplex with embryonal hair formation: case presentation and consideration of pathogenesis. AMA Arch Derm. 1957;76:720-725.
  25. Sohn D, Chin TC, Fellner MJ. Multiple keratoacanthomas associated with steatocystoma multiplex and rheumatoid arthritis: a case report. Arch Dermatol. 1980;116:913-915.
  26. Verbov J. Acrokeratosis verruciformis of Hopf with steatocystoma multiplex and hypertrophic lichen planus. Br J Dermatol. 1972;86:91-94.
  27. Esterly NB, Fretzin DF, Pinkus H. Eruptive vellus hair cysts. Arch Dermatol. 1977;113:500-503.
  28. Tomkova H, Fujimoto W, Arata J. Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus hair cysts, and epidermoid and trichilemmal cysts. Am J Dermatopathol. 1997;19:250-253.
  29. Feinstein A, Trau H, Movshovitz M, et al. Steatocystoma multiplex. Cutis. 1983;31:425-427.
References
  1. Cho S, Chang SE, Choi JH, et al. Clinical and histologic features of 64 cases of steatocystoma multiplex. J Dermatol. 2002;29:152-156.
  2. Ogawa Y, Nogita T, Kawashima M. The coexistence of eruptive vellus hair cysts and steatocystoma multiplex. J Dermatol. 1992;19:570-571.
  3. Sanchez Yus E, Requena L. Eruptive vellus hair cyst and steatocystoma multiplex. Am J Dermatopathol. 1990;12:536-537.
  4. Patrizi A, Neri I, Guerrini V, et al. Persistent milia, steatocystoma multiplex and eruptive vellus hair cysts: variable expression of multiple pilosebaceous cysts within an affected family. Dermatology. 1998;196:392-396.
  5. Ohtake N, Kubota Y, Takayama O, et al. Relationship between steatocystoma multiplex and eruptive vellus hair cysts. J Am Acad Dermatol. 1992;26(5, pt 2):876-878.
  6. Kiene P, Hauschild A, Christophers E. Eruptive vellus hair cysts and steatocystoma multiplex: variants of one entity? Br J Dermatol. 1996;134:365-367.
  7. Hurlimann AF, Panizzon RG, Burg G. Eruptive vellus hair cyst and steatocystoma multiplex: hybrid cysts. Dermatology. 1996;192:64-66.
  8. Sexton M, Murdock DK. Eruptive vellus hair cysts: a follicular cyst of the sebaceous duct (sometimes). Am J Dermatopathol. 1989;11:364-368.
  9. Sanchez-Yus E, Aguilar-Martinez A, Cristobal-Gil MC, et al. Eruptive vellus hair cyst and steatocystoma multiplex: two related conditions? J Cutan Pathol. 1988;15:40-42.
  10. Ahn SK, Chung J, Lee WS, et al. Hybrid cysts showing alternate combination of eruptive vellus hair cyst, steatocystoma multiplex, and epidermoid cyst, and an association among the three conditions. Am J Dermatopathol. 1996;18:645-649.
  11. Ahn SK, Hwang SM, Lee SH, et al. Steatocystoma multiplex localized only in the face. Int J Dermatol. 1997;36:372-373.
  12. Cole LA. Steatocystoma multiplex. Arch Dermatol. 1976;112:1437-1439.
  13. Hansen KK, Troy JL, Fairley JA. Multiple papules of the scalp and forehead. steatocystoma multiplex (facial papular variant). Arch Dermatol. 1995;131:835-838.
  14. Nishimura M, Kohda H, Urabe A. Steatocystoma multiplex: a facial popular variant. Arch Dermatol. 1986;122:205-207.
  15. Requena L, Martin L, Renedo G, et al. A facial variant of steatocystoma multiplex. Cutis. 1993;51:449-452.
  16. Holmes R, Black MM. Steatocystoma multiplex with unusually prominent cysts on the face. Br J Dermatol. 1980;102:711-713.
  17. Kumakiri M, Takashima I, Iju M, et al. Eruptive vellus hair cysts: a facial variant. J Am Acad Dermatol. 1982;7:461-467.
  18. Gianotti R, Cavicchini S, Alessi E. Simultaneous occurrence of multiple trichoblastomas and steatocystoma multiplex. Am J Dermatopathol. 1997;19:294-298.
  19. Sardana K, Sharma RC, Jain A, et al. Facial steatocystoma multiplex associated with pilar cyst and bilateral preauricular sinus. J Dermatol. 2002;29:157-159.
  20. Mount LB. Steatocystoma multiplex. Arch Dermatol Syphilol. 1937;36:31-39.
  21. Dubreuilh W, Auche B. Kystes grassieux sudoripares. Arch Clin de Bordeaux. 1896;5:387-391.
  22. Pringle JJ. A case of peculiar multiple sebaceous cysts (steatocystoma multiplex). Br J Dermatol. 1899;11:381-88.
  23. Vineyard WR, Scott RA. Steatocystoma multiplex with pachyonychia congenital: eight cases in four generations. Arch Dermatol. 1961;84:824-827.
  24. Contreras MA, Costello MJ. Steatocystoma multiplex with embryonal hair formation: case presentation and consideration of pathogenesis. AMA Arch Derm. 1957;76:720-725.
  25. Sohn D, Chin TC, Fellner MJ. Multiple keratoacanthomas associated with steatocystoma multiplex and rheumatoid arthritis: a case report. Arch Dermatol. 1980;116:913-915.
  26. Verbov J. Acrokeratosis verruciformis of Hopf with steatocystoma multiplex and hypertrophic lichen planus. Br J Dermatol. 1972;86:91-94.
  27. Esterly NB, Fretzin DF, Pinkus H. Eruptive vellus hair cysts. Arch Dermatol. 1977;113:500-503.
  28. Tomkova H, Fujimoto W, Arata J. Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus hair cysts, and epidermoid and trichilemmal cysts. Am J Dermatopathol. 1997;19:250-253.
  29. Feinstein A, Trau H, Movshovitz M, et al. Steatocystoma multiplex. Cutis. 1983;31:425-427.
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Co-occurrence of Steatocystoma Multiplex, Eruptive Vellus Hair Cysts, and Trichofolliculomas
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  • Steatocystoma multiplex (SCM) and eruptive vellus hair cysts (EVHCs) have similar clinical features but distinctive histologic features.
  • Milia, pilar cyst, trichoepitheliomas, and trichoblastomas simultaneously developing in association with SCM or EVHC on the face are rare.
  • This case supports the hypothesis that these benign follicular neoplasms are related but distinct nevoid malformations of the pilosebaceous unit within the same disease spectrum.
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No, you still can’t diagnose Trump

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On the morning of July 25, I scrolled through my Twitter account to see tweets flying: Psychiatrists can now defy the Goldwater Rule! Oops, wrong organization; no ,they can’t. Over the course of the day, articles appeared in Scientific American, the Los Angeles Times, Newsweek, International Business Times; and statements were issued by both the American Psychiatric Association and the American Psychoanalytic Association.

So what happened?

Dr. Dinah Miller
At the annual meeting of the American Psychoanalytic Association – an organization of 3,500 interdisciplinary mental health professionals – its executive councilors were polled about whether they endorsed APsaA’s existing policy that allows for the organization’s comments on sociopolitical issues and not on specific political figures. The vote was unanimous to continue with its existing policy of commenting on issues, not individuals.

On July 6, 2017, the ApsaA had sent an email to all its members informing them of this decision. The email also stated: “However, it is important to note that members of APsaA are free to comment about political figures as individuals. The American Psychiatric Association’s ethical stance on the Goldwater Rule applies to its members only. The APsaA does not consider political commentary by its individual members an ethical matter.” (Bolding per the email). This was not considered to be a change in its policy.

Citing that email, on July 25, STAT reporter Sharon Begley wrote an article titled, “Psychiatry group tells members they can ignore ‘Goldwater rule’ and comment on Trump’s mental health.” The article was linked to on Twitter, and the retweets and comments started to fly. As a single example, Josh Marshall, editor and publisher of Talking Points Memo, tweeted out to his 215,000 followers: “Truly amazing am psych assoc says Trump so f’ing nuts they’re lifting Goldwater Rule.” The APA issued several statements over the course of the day, notably: “We are the largest psychiatric organization in the world with more than 37,000 members. The Goldwater Rules applies to our members.” Commenters expressed frustration with the Goldwater Rule, and suggested that the APA had a duty to warn.

Shortly after noon that day, the APsaA put a statement on its website to clarify information in the STAT article: “In an email to association members, our leadership did not encourage members to defy the “Goldwater Rule” which is a part of the ethics code of a different mental health organization, the American Psychiatric Association (APA). Rather, it articulated a distinct ethics position that represents the viewpoint of psychoanalysts. The field of psychoanalysis addresses the full spectrum of human behavior, and we feel that our concepts and understanding are applicable and valuable to understanding a wide range of human behaviors and cultural phenomenon.”

Later in the afternoon, I spoke with Wylie Tene, director of pubic affairs for the APsaA. He noted: “The article in StatNews had a misleading and sensational headline. It didn’t represent what our email was about.”

I found it interesting that a sensational headline on STAT’s website could lead to so much comment and so many articles in major news outlets. July 25, 2017, was not a slow news day: John McCain (R-Ariz) returned to the Senate that day and voted to proceed with the debate to repeal Obamacare. A single vote cast by Vice President Mike Pence broke the tie, allowing the debate to go forward.

Like many, I feel conflicted about the Goldwater Rule but for a single reason: I am a strong believer in free speech, and the rule squelches psychiatrists. But as I noted in a column in August 2016, I don’t believe that our opinions should, would, or could change our political environment. Psychiatric treatment is about compassion and healing, and diagnoses are based on symptoms that patients often tell us about in a setting of intimacy and trust. Diagnosing celebrities, on the other hand, is often about name calling; it risks insulting our patients and perpetuating stigma.

Regarding Mr. Trump, I’m going to finish with the same words I wrote back in August, prior to his election as president. You’ll note that my insights in Clinical Psychiatry News and circulated on the Internet – devoid of a diagnosis – did not influence the outcome of the general election. Psychiatric diagnoses are made by observing a constellation of symptoms that occur together.

Mr. Trump has given the whole world years of data – he’s lived his life in a very public way. As a real estate developer, he has had countless employees who all know how they’ve been treated. We’ve seen him through three marriages and watched how he interacts with his children. We’ve seen him take out full-page ads calling for the death penalty for a group of young men who were wrongly convicted in the rape and assault of the Central Park jogger in 1989. If that’s not enough, he has hosted his own reality television show, and we’ve now seen him countless times in debates and rallies. We know how he treats his running mates, journalist Megyn Kelly, a news reporter with a disability, and the parents of a fallen soldier. We’ve watched him allude to the size of his genitals during a primary debate. Every individual is free to decide if Mr. Trump’s widely viewed patterns of behavior represent much-needed spunk and change with political beliefs that align with their own, or if his words and behaviors represent cruelty, impulsivity, poor judgment, and a pattern of actions that some might not feel is dignified enough for our country’s leader. No degree is required to observe and draw conclusions.
 
 

 

Dr. Miller, who practices in Baltimore, is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).

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On the morning of July 25, I scrolled through my Twitter account to see tweets flying: Psychiatrists can now defy the Goldwater Rule! Oops, wrong organization; no ,they can’t. Over the course of the day, articles appeared in Scientific American, the Los Angeles Times, Newsweek, International Business Times; and statements were issued by both the American Psychiatric Association and the American Psychoanalytic Association.

So what happened?

Dr. Dinah Miller
At the annual meeting of the American Psychoanalytic Association – an organization of 3,500 interdisciplinary mental health professionals – its executive councilors were polled about whether they endorsed APsaA’s existing policy that allows for the organization’s comments on sociopolitical issues and not on specific political figures. The vote was unanimous to continue with its existing policy of commenting on issues, not individuals.

On July 6, 2017, the ApsaA had sent an email to all its members informing them of this decision. The email also stated: “However, it is important to note that members of APsaA are free to comment about political figures as individuals. The American Psychiatric Association’s ethical stance on the Goldwater Rule applies to its members only. The APsaA does not consider political commentary by its individual members an ethical matter.” (Bolding per the email). This was not considered to be a change in its policy.

Citing that email, on July 25, STAT reporter Sharon Begley wrote an article titled, “Psychiatry group tells members they can ignore ‘Goldwater rule’ and comment on Trump’s mental health.” The article was linked to on Twitter, and the retweets and comments started to fly. As a single example, Josh Marshall, editor and publisher of Talking Points Memo, tweeted out to his 215,000 followers: “Truly amazing am psych assoc says Trump so f’ing nuts they’re lifting Goldwater Rule.” The APA issued several statements over the course of the day, notably: “We are the largest psychiatric organization in the world with more than 37,000 members. The Goldwater Rules applies to our members.” Commenters expressed frustration with the Goldwater Rule, and suggested that the APA had a duty to warn.

Shortly after noon that day, the APsaA put a statement on its website to clarify information in the STAT article: “In an email to association members, our leadership did not encourage members to defy the “Goldwater Rule” which is a part of the ethics code of a different mental health organization, the American Psychiatric Association (APA). Rather, it articulated a distinct ethics position that represents the viewpoint of psychoanalysts. The field of psychoanalysis addresses the full spectrum of human behavior, and we feel that our concepts and understanding are applicable and valuable to understanding a wide range of human behaviors and cultural phenomenon.”

Later in the afternoon, I spoke with Wylie Tene, director of pubic affairs for the APsaA. He noted: “The article in StatNews had a misleading and sensational headline. It didn’t represent what our email was about.”

I found it interesting that a sensational headline on STAT’s website could lead to so much comment and so many articles in major news outlets. July 25, 2017, was not a slow news day: John McCain (R-Ariz) returned to the Senate that day and voted to proceed with the debate to repeal Obamacare. A single vote cast by Vice President Mike Pence broke the tie, allowing the debate to go forward.

Like many, I feel conflicted about the Goldwater Rule but for a single reason: I am a strong believer in free speech, and the rule squelches psychiatrists. But as I noted in a column in August 2016, I don’t believe that our opinions should, would, or could change our political environment. Psychiatric treatment is about compassion and healing, and diagnoses are based on symptoms that patients often tell us about in a setting of intimacy and trust. Diagnosing celebrities, on the other hand, is often about name calling; it risks insulting our patients and perpetuating stigma.

Regarding Mr. Trump, I’m going to finish with the same words I wrote back in August, prior to his election as president. You’ll note that my insights in Clinical Psychiatry News and circulated on the Internet – devoid of a diagnosis – did not influence the outcome of the general election. Psychiatric diagnoses are made by observing a constellation of symptoms that occur together.

Mr. Trump has given the whole world years of data – he’s lived his life in a very public way. As a real estate developer, he has had countless employees who all know how they’ve been treated. We’ve seen him through three marriages and watched how he interacts with his children. We’ve seen him take out full-page ads calling for the death penalty for a group of young men who were wrongly convicted in the rape and assault of the Central Park jogger in 1989. If that’s not enough, he has hosted his own reality television show, and we’ve now seen him countless times in debates and rallies. We know how he treats his running mates, journalist Megyn Kelly, a news reporter with a disability, and the parents of a fallen soldier. We’ve watched him allude to the size of his genitals during a primary debate. Every individual is free to decide if Mr. Trump’s widely viewed patterns of behavior represent much-needed spunk and change with political beliefs that align with their own, or if his words and behaviors represent cruelty, impulsivity, poor judgment, and a pattern of actions that some might not feel is dignified enough for our country’s leader. No degree is required to observe and draw conclusions.
 
 

 

Dr. Miller, who practices in Baltimore, is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).

 

On the morning of July 25, I scrolled through my Twitter account to see tweets flying: Psychiatrists can now defy the Goldwater Rule! Oops, wrong organization; no ,they can’t. Over the course of the day, articles appeared in Scientific American, the Los Angeles Times, Newsweek, International Business Times; and statements were issued by both the American Psychiatric Association and the American Psychoanalytic Association.

So what happened?

Dr. Dinah Miller
At the annual meeting of the American Psychoanalytic Association – an organization of 3,500 interdisciplinary mental health professionals – its executive councilors were polled about whether they endorsed APsaA’s existing policy that allows for the organization’s comments on sociopolitical issues and not on specific political figures. The vote was unanimous to continue with its existing policy of commenting on issues, not individuals.

On July 6, 2017, the ApsaA had sent an email to all its members informing them of this decision. The email also stated: “However, it is important to note that members of APsaA are free to comment about political figures as individuals. The American Psychiatric Association’s ethical stance on the Goldwater Rule applies to its members only. The APsaA does not consider political commentary by its individual members an ethical matter.” (Bolding per the email). This was not considered to be a change in its policy.

Citing that email, on July 25, STAT reporter Sharon Begley wrote an article titled, “Psychiatry group tells members they can ignore ‘Goldwater rule’ and comment on Trump’s mental health.” The article was linked to on Twitter, and the retweets and comments started to fly. As a single example, Josh Marshall, editor and publisher of Talking Points Memo, tweeted out to his 215,000 followers: “Truly amazing am psych assoc says Trump so f’ing nuts they’re lifting Goldwater Rule.” The APA issued several statements over the course of the day, notably: “We are the largest psychiatric organization in the world with more than 37,000 members. The Goldwater Rules applies to our members.” Commenters expressed frustration with the Goldwater Rule, and suggested that the APA had a duty to warn.

Shortly after noon that day, the APsaA put a statement on its website to clarify information in the STAT article: “In an email to association members, our leadership did not encourage members to defy the “Goldwater Rule” which is a part of the ethics code of a different mental health organization, the American Psychiatric Association (APA). Rather, it articulated a distinct ethics position that represents the viewpoint of psychoanalysts. The field of psychoanalysis addresses the full spectrum of human behavior, and we feel that our concepts and understanding are applicable and valuable to understanding a wide range of human behaviors and cultural phenomenon.”

Later in the afternoon, I spoke with Wylie Tene, director of pubic affairs for the APsaA. He noted: “The article in StatNews had a misleading and sensational headline. It didn’t represent what our email was about.”

I found it interesting that a sensational headline on STAT’s website could lead to so much comment and so many articles in major news outlets. July 25, 2017, was not a slow news day: John McCain (R-Ariz) returned to the Senate that day and voted to proceed with the debate to repeal Obamacare. A single vote cast by Vice President Mike Pence broke the tie, allowing the debate to go forward.

Like many, I feel conflicted about the Goldwater Rule but for a single reason: I am a strong believer in free speech, and the rule squelches psychiatrists. But as I noted in a column in August 2016, I don’t believe that our opinions should, would, or could change our political environment. Psychiatric treatment is about compassion and healing, and diagnoses are based on symptoms that patients often tell us about in a setting of intimacy and trust. Diagnosing celebrities, on the other hand, is often about name calling; it risks insulting our patients and perpetuating stigma.

Regarding Mr. Trump, I’m going to finish with the same words I wrote back in August, prior to his election as president. You’ll note that my insights in Clinical Psychiatry News and circulated on the Internet – devoid of a diagnosis – did not influence the outcome of the general election. Psychiatric diagnoses are made by observing a constellation of symptoms that occur together.

Mr. Trump has given the whole world years of data – he’s lived his life in a very public way. As a real estate developer, he has had countless employees who all know how they’ve been treated. We’ve seen him through three marriages and watched how he interacts with his children. We’ve seen him take out full-page ads calling for the death penalty for a group of young men who were wrongly convicted in the rape and assault of the Central Park jogger in 1989. If that’s not enough, he has hosted his own reality television show, and we’ve now seen him countless times in debates and rallies. We know how he treats his running mates, journalist Megyn Kelly, a news reporter with a disability, and the parents of a fallen soldier. We’ve watched him allude to the size of his genitals during a primary debate. Every individual is free to decide if Mr. Trump’s widely viewed patterns of behavior represent much-needed spunk and change with political beliefs that align with their own, or if his words and behaviors represent cruelty, impulsivity, poor judgment, and a pattern of actions that some might not feel is dignified enough for our country’s leader. No degree is required to observe and draw conclusions.
 
 

 

Dr. Miller, who practices in Baltimore, is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).

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Pediatric News welcomes Dr. Kelly Curran

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Pediatric News welcomes Kelly Curran, MD, MA, to its Editorial Advisory Board.

Dr. Curran is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, practicing adolescent medicine. Dr. Curran is member of the Society for Adolescent Health and Medicine and the American Academy of Pediatrics, where she serves as an editorial board member for the AAP’s Adolescent Medicine PREP series. Her areas of interest include bioethics, reproductive health care, and adolescent mental health care.

Dr. Kelly Curran
She graduated from Loyola University Chicago’s Stritch School of Medicine, Maywood, Ill., served her residency in internal medicine and pediatrics at the Medical College of Wisconsin, Milwaukee, and served as a clinical fellow in adolescent medicine at the Children’s Hospital of Wisconsin, Milwaukee. She also graduated from Loyola University with a master of arts in bioethics and health policy.
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Pediatric News welcomes Kelly Curran, MD, MA, to its Editorial Advisory Board.

Dr. Curran is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, practicing adolescent medicine. Dr. Curran is member of the Society for Adolescent Health and Medicine and the American Academy of Pediatrics, where she serves as an editorial board member for the AAP’s Adolescent Medicine PREP series. Her areas of interest include bioethics, reproductive health care, and adolescent mental health care.

Dr. Kelly Curran
She graduated from Loyola University Chicago’s Stritch School of Medicine, Maywood, Ill., served her residency in internal medicine and pediatrics at the Medical College of Wisconsin, Milwaukee, and served as a clinical fellow in adolescent medicine at the Children’s Hospital of Wisconsin, Milwaukee. She also graduated from Loyola University with a master of arts in bioethics and health policy.

 

Pediatric News welcomes Kelly Curran, MD, MA, to its Editorial Advisory Board.

Dr. Curran is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, practicing adolescent medicine. Dr. Curran is member of the Society for Adolescent Health and Medicine and the American Academy of Pediatrics, where she serves as an editorial board member for the AAP’s Adolescent Medicine PREP series. Her areas of interest include bioethics, reproductive health care, and adolescent mental health care.

Dr. Kelly Curran
She graduated from Loyola University Chicago’s Stritch School of Medicine, Maywood, Ill., served her residency in internal medicine and pediatrics at the Medical College of Wisconsin, Milwaukee, and served as a clinical fellow in adolescent medicine at the Children’s Hospital of Wisconsin, Milwaukee. She also graduated from Loyola University with a master of arts in bioethics and health policy.
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50 years of pediatrics: What has changed for female pediatricians?

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In the last 50 years, the field of pediatrics has vastly changed, particularly for female physicians.

For starters, the number of female pediatricians has rapidly grown over the last few decades. In 1970, 21% of pediatricians were women, compared with 59% in 2013, according to the American Medical Association physician characteristics and distribution data 2015 edition. The overall pediatric workforce also has increased: A total of 18,332 pediatricians were practicing in 1970, and 84,559 pediatricians were in practice in 2013.

Along with numbers, the field of pediatrics has seen significant changes in practice size, technology, clinical responsibilities, and record keeping, to name a few. However, longtime pediatricians say there are also many ways that the specialty has stayed the same. Two female pediatricians share their memories of practicing in 1967 and offer guidance to young pediatricians about practicing today.
 

Dr. Bennett’s story

When Jean L. Bennett, MD, opened her solo pediatric practice in 1963, she initially had no nurses or team of assistants to help carry out clinical duties. With one receptionist answering phones and Dr. Bennett in the exam room, the Clearwater, Fla., practice opened for business. There was no shortage of patients, Dr. Bennett recalls.

“There was no such thing as neonatology. As a pediatrician, one took care of well and sick newborns and of course, saw a variety of infectious diseases in the office,” Dr. Bennett said in an interview. “We started our own IVs, we did our own lumbar punctures, we did subdural taps, we did exchange transfusions. We did all of those ourselves.”

Dr. Jean L. Bennett
At the time, Dr. Bennett was the only female pediatrician in the area with a solo practice. Five male pediatricians operated independent practices nearby. Although separate, the six pediatricians operated “like a family,” she said. The doctors held regular meetings, discussed medical cases, and took call for one another.

Dr. Bennett was no stranger to being the lone woman on the job. She was the first woman to graduate from the University of Florida College of Medicine in Gainesville, the first woman to serve as chief of staff at Morton F. Plant Hospital in Clearwater, and the first woman to chair the hospital’s department of pediatrics. Despite being the first in many cases, Dr. Bennett does not remember facing discrimination from colleagues or community members, nor experiencing prejudice against her gender as a medical student or young resident

“My experience was different, of course, than other people graduating at that time, but I can truly say that I always felt the playing field was level,” Dr. Bennett said. “Nobody gave me anything for being a woman, and nobody took anything away.”

Compared with concerns that physicians have today, such as electronic medical records and increasing regulations, Dr. Bennett remembers a relatively worry-free career. She recalls some concern over the medical malpractice crisis in the 1970s and 1980s, but said the majority of her tenure was spent with a clear mind and positive attitude.

“In the 60s, I was naive enough not to worry a whole lot,” she said. “I was in the process of getting my practice started, and I was raising in a family at the same time. I would struggle to tell you the things I spent time worrying about. I went to work every day with a joyful attitude, grateful that I was in a community where I could serve.”

Two of the most significant changes Dr. Bennett witnessed during her career were the development of pediatric subspecialists and the establishment of children’s hospitals. Both markedly altered the field of pediatrics and the way in which children were cared for, she said.

“Early in medicine, children were thought of as the stepchildren of medicine, if you will,” she said. “All the attention research-wise and provision-wise was for adults. During my tenure, I saw that attitude change. The attitude that children were just little adults certainly changed, and the development of specialty hospitals for children, that was a real plus.”

Dr. Bennett spent 27 years in solo practice before hiring additional doctors at what is now Myrtle Avenue Pediatrics, a group practice in Clearwater. She retired in 2003 after a career spanning 40 years. The best advice she would offer young pediatricians is to treat their staff well, especially the front office staff who answer phones and make appointments. Pay them well, train them, and treat them right in order to retain loyal employees and reduce turnover.

In addition, Dr. Bennett stresses that young women who want to be pediatricians should not focus on their gender. “I would remind them that they are physicians who happen to be women,” and they should not think of themselves as female physicians, she said. “Personally I believe becoming a physician is a calling, and I don’t think it is gender oriented. I think males and females can have that calling. I see no difference.”
 
 

 

Dr. Eaton’s story

In the 1960s, when most young pediatricians were opening practices or joining small groups, Antoinette P. Eaton, MD, chose an different path. A passion for serving undeserved families led her to back to what is now Nationwide Children’s Hospital in Columbus, Ohio, where she had completed her residency. In the early 60s, Dr. Eaton served as assistant medical director at the hospital, and in 1965 she become director of the hospital’s birth defect center.

Back then, insurers operated much differently, Dr. Eaton recalled. Insurance companies would not pay for outpatient care, and so children with developmental or congenital disorders would have to be admitted to the hospital for treatment. “It was a complete reversal of what it is like now,” she said.

Dr. Antoinette P. Eaton
From 1965 until about 1975, Dr. Eaton spent her days caring for children with developmental delays, cognitive disorders, and genetic malformations. Although multilevel medical teams were not yet common, she worked with a diverse team at the birth defect center that included a psychologist, a social worker, a nurse, and physical and occupational therapists.

“We all saw each patient, and then we would get together and conference on the patient and decide on the best approach,” Dr. Eaton said in an interview. “I would definitely say it was unique. It certainly ingrained in me how valuable the team approach to medicine was then and is now. It’s become a very popular approach, and I’m happy to see that, but that was my approach way back in the mid-60s and mid-70s.”

Like female pediatricians of today, Dr. Eaton worked to juggle her career and her role as a mother to four children. She found balance by working part time when necessary and getting off early when her children were school-aged. “Being a mother and being a physician, especially in leadership, there’s always going to be pressure for allocating your time appropriately between all of those demands, but I can tell you I always made being a mother my top priority, and I don’t think I sacrificed my professional duties as a result,” she said. “I think it was possible to combine them, although it’s certainly challenging at times.”

Dr. Eaton went on to become director for maternal health at the Ohio Department of Health and later served as president for the AAP Ohio Chapter and as AAP president from 1990 to 1991.

Her most important achievement however, was being a strong voice for children, she said. “My biggest accomplishment, I hope, was standing up for children and speaking out for children and assuming leadership roles in organizations like AAP to underscore that important role as an advocate.”
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In the last 50 years, the field of pediatrics has vastly changed, particularly for female physicians.

For starters, the number of female pediatricians has rapidly grown over the last few decades. In 1970, 21% of pediatricians were women, compared with 59% in 2013, according to the American Medical Association physician characteristics and distribution data 2015 edition. The overall pediatric workforce also has increased: A total of 18,332 pediatricians were practicing in 1970, and 84,559 pediatricians were in practice in 2013.

Along with numbers, the field of pediatrics has seen significant changes in practice size, technology, clinical responsibilities, and record keeping, to name a few. However, longtime pediatricians say there are also many ways that the specialty has stayed the same. Two female pediatricians share their memories of practicing in 1967 and offer guidance to young pediatricians about practicing today.
 

Dr. Bennett’s story

When Jean L. Bennett, MD, opened her solo pediatric practice in 1963, she initially had no nurses or team of assistants to help carry out clinical duties. With one receptionist answering phones and Dr. Bennett in the exam room, the Clearwater, Fla., practice opened for business. There was no shortage of patients, Dr. Bennett recalls.

“There was no such thing as neonatology. As a pediatrician, one took care of well and sick newborns and of course, saw a variety of infectious diseases in the office,” Dr. Bennett said in an interview. “We started our own IVs, we did our own lumbar punctures, we did subdural taps, we did exchange transfusions. We did all of those ourselves.”

Dr. Jean L. Bennett
At the time, Dr. Bennett was the only female pediatrician in the area with a solo practice. Five male pediatricians operated independent practices nearby. Although separate, the six pediatricians operated “like a family,” she said. The doctors held regular meetings, discussed medical cases, and took call for one another.

Dr. Bennett was no stranger to being the lone woman on the job. She was the first woman to graduate from the University of Florida College of Medicine in Gainesville, the first woman to serve as chief of staff at Morton F. Plant Hospital in Clearwater, and the first woman to chair the hospital’s department of pediatrics. Despite being the first in many cases, Dr. Bennett does not remember facing discrimination from colleagues or community members, nor experiencing prejudice against her gender as a medical student or young resident

“My experience was different, of course, than other people graduating at that time, but I can truly say that I always felt the playing field was level,” Dr. Bennett said. “Nobody gave me anything for being a woman, and nobody took anything away.”

Compared with concerns that physicians have today, such as electronic medical records and increasing regulations, Dr. Bennett remembers a relatively worry-free career. She recalls some concern over the medical malpractice crisis in the 1970s and 1980s, but said the majority of her tenure was spent with a clear mind and positive attitude.

“In the 60s, I was naive enough not to worry a whole lot,” she said. “I was in the process of getting my practice started, and I was raising in a family at the same time. I would struggle to tell you the things I spent time worrying about. I went to work every day with a joyful attitude, grateful that I was in a community where I could serve.”

Two of the most significant changes Dr. Bennett witnessed during her career were the development of pediatric subspecialists and the establishment of children’s hospitals. Both markedly altered the field of pediatrics and the way in which children were cared for, she said.

“Early in medicine, children were thought of as the stepchildren of medicine, if you will,” she said. “All the attention research-wise and provision-wise was for adults. During my tenure, I saw that attitude change. The attitude that children were just little adults certainly changed, and the development of specialty hospitals for children, that was a real plus.”

Dr. Bennett spent 27 years in solo practice before hiring additional doctors at what is now Myrtle Avenue Pediatrics, a group practice in Clearwater. She retired in 2003 after a career spanning 40 years. The best advice she would offer young pediatricians is to treat their staff well, especially the front office staff who answer phones and make appointments. Pay them well, train them, and treat them right in order to retain loyal employees and reduce turnover.

In addition, Dr. Bennett stresses that young women who want to be pediatricians should not focus on their gender. “I would remind them that they are physicians who happen to be women,” and they should not think of themselves as female physicians, she said. “Personally I believe becoming a physician is a calling, and I don’t think it is gender oriented. I think males and females can have that calling. I see no difference.”
 
 

 

Dr. Eaton’s story

In the 1960s, when most young pediatricians were opening practices or joining small groups, Antoinette P. Eaton, MD, chose an different path. A passion for serving undeserved families led her to back to what is now Nationwide Children’s Hospital in Columbus, Ohio, where she had completed her residency. In the early 60s, Dr. Eaton served as assistant medical director at the hospital, and in 1965 she become director of the hospital’s birth defect center.

Back then, insurers operated much differently, Dr. Eaton recalled. Insurance companies would not pay for outpatient care, and so children with developmental or congenital disorders would have to be admitted to the hospital for treatment. “It was a complete reversal of what it is like now,” she said.

Dr. Antoinette P. Eaton
From 1965 until about 1975, Dr. Eaton spent her days caring for children with developmental delays, cognitive disorders, and genetic malformations. Although multilevel medical teams were not yet common, she worked with a diverse team at the birth defect center that included a psychologist, a social worker, a nurse, and physical and occupational therapists.

“We all saw each patient, and then we would get together and conference on the patient and decide on the best approach,” Dr. Eaton said in an interview. “I would definitely say it was unique. It certainly ingrained in me how valuable the team approach to medicine was then and is now. It’s become a very popular approach, and I’m happy to see that, but that was my approach way back in the mid-60s and mid-70s.”

Like female pediatricians of today, Dr. Eaton worked to juggle her career and her role as a mother to four children. She found balance by working part time when necessary and getting off early when her children were school-aged. “Being a mother and being a physician, especially in leadership, there’s always going to be pressure for allocating your time appropriately between all of those demands, but I can tell you I always made being a mother my top priority, and I don’t think I sacrificed my professional duties as a result,” she said. “I think it was possible to combine them, although it’s certainly challenging at times.”

Dr. Eaton went on to become director for maternal health at the Ohio Department of Health and later served as president for the AAP Ohio Chapter and as AAP president from 1990 to 1991.

Her most important achievement however, was being a strong voice for children, she said. “My biggest accomplishment, I hope, was standing up for children and speaking out for children and assuming leadership roles in organizations like AAP to underscore that important role as an advocate.”

 

In the last 50 years, the field of pediatrics has vastly changed, particularly for female physicians.

For starters, the number of female pediatricians has rapidly grown over the last few decades. In 1970, 21% of pediatricians were women, compared with 59% in 2013, according to the American Medical Association physician characteristics and distribution data 2015 edition. The overall pediatric workforce also has increased: A total of 18,332 pediatricians were practicing in 1970, and 84,559 pediatricians were in practice in 2013.

Along with numbers, the field of pediatrics has seen significant changes in practice size, technology, clinical responsibilities, and record keeping, to name a few. However, longtime pediatricians say there are also many ways that the specialty has stayed the same. Two female pediatricians share their memories of practicing in 1967 and offer guidance to young pediatricians about practicing today.
 

Dr. Bennett’s story

When Jean L. Bennett, MD, opened her solo pediatric practice in 1963, she initially had no nurses or team of assistants to help carry out clinical duties. With one receptionist answering phones and Dr. Bennett in the exam room, the Clearwater, Fla., practice opened for business. There was no shortage of patients, Dr. Bennett recalls.

“There was no such thing as neonatology. As a pediatrician, one took care of well and sick newborns and of course, saw a variety of infectious diseases in the office,” Dr. Bennett said in an interview. “We started our own IVs, we did our own lumbar punctures, we did subdural taps, we did exchange transfusions. We did all of those ourselves.”

Dr. Jean L. Bennett
At the time, Dr. Bennett was the only female pediatrician in the area with a solo practice. Five male pediatricians operated independent practices nearby. Although separate, the six pediatricians operated “like a family,” she said. The doctors held regular meetings, discussed medical cases, and took call for one another.

Dr. Bennett was no stranger to being the lone woman on the job. She was the first woman to graduate from the University of Florida College of Medicine in Gainesville, the first woman to serve as chief of staff at Morton F. Plant Hospital in Clearwater, and the first woman to chair the hospital’s department of pediatrics. Despite being the first in many cases, Dr. Bennett does not remember facing discrimination from colleagues or community members, nor experiencing prejudice against her gender as a medical student or young resident

“My experience was different, of course, than other people graduating at that time, but I can truly say that I always felt the playing field was level,” Dr. Bennett said. “Nobody gave me anything for being a woman, and nobody took anything away.”

Compared with concerns that physicians have today, such as electronic medical records and increasing regulations, Dr. Bennett remembers a relatively worry-free career. She recalls some concern over the medical malpractice crisis in the 1970s and 1980s, but said the majority of her tenure was spent with a clear mind and positive attitude.

“In the 60s, I was naive enough not to worry a whole lot,” she said. “I was in the process of getting my practice started, and I was raising in a family at the same time. I would struggle to tell you the things I spent time worrying about. I went to work every day with a joyful attitude, grateful that I was in a community where I could serve.”

Two of the most significant changes Dr. Bennett witnessed during her career were the development of pediatric subspecialists and the establishment of children’s hospitals. Both markedly altered the field of pediatrics and the way in which children were cared for, she said.

“Early in medicine, children were thought of as the stepchildren of medicine, if you will,” she said. “All the attention research-wise and provision-wise was for adults. During my tenure, I saw that attitude change. The attitude that children were just little adults certainly changed, and the development of specialty hospitals for children, that was a real plus.”

Dr. Bennett spent 27 years in solo practice before hiring additional doctors at what is now Myrtle Avenue Pediatrics, a group practice in Clearwater. She retired in 2003 after a career spanning 40 years. The best advice she would offer young pediatricians is to treat their staff well, especially the front office staff who answer phones and make appointments. Pay them well, train them, and treat them right in order to retain loyal employees and reduce turnover.

In addition, Dr. Bennett stresses that young women who want to be pediatricians should not focus on their gender. “I would remind them that they are physicians who happen to be women,” and they should not think of themselves as female physicians, she said. “Personally I believe becoming a physician is a calling, and I don’t think it is gender oriented. I think males and females can have that calling. I see no difference.”
 
 

 

Dr. Eaton’s story

In the 1960s, when most young pediatricians were opening practices or joining small groups, Antoinette P. Eaton, MD, chose an different path. A passion for serving undeserved families led her to back to what is now Nationwide Children’s Hospital in Columbus, Ohio, where she had completed her residency. In the early 60s, Dr. Eaton served as assistant medical director at the hospital, and in 1965 she become director of the hospital’s birth defect center.

Back then, insurers operated much differently, Dr. Eaton recalled. Insurance companies would not pay for outpatient care, and so children with developmental or congenital disorders would have to be admitted to the hospital for treatment. “It was a complete reversal of what it is like now,” she said.

Dr. Antoinette P. Eaton
From 1965 until about 1975, Dr. Eaton spent her days caring for children with developmental delays, cognitive disorders, and genetic malformations. Although multilevel medical teams were not yet common, she worked with a diverse team at the birth defect center that included a psychologist, a social worker, a nurse, and physical and occupational therapists.

“We all saw each patient, and then we would get together and conference on the patient and decide on the best approach,” Dr. Eaton said in an interview. “I would definitely say it was unique. It certainly ingrained in me how valuable the team approach to medicine was then and is now. It’s become a very popular approach, and I’m happy to see that, but that was my approach way back in the mid-60s and mid-70s.”

Like female pediatricians of today, Dr. Eaton worked to juggle her career and her role as a mother to four children. She found balance by working part time when necessary and getting off early when her children were school-aged. “Being a mother and being a physician, especially in leadership, there’s always going to be pressure for allocating your time appropriately between all of those demands, but I can tell you I always made being a mother my top priority, and I don’t think I sacrificed my professional duties as a result,” she said. “I think it was possible to combine them, although it’s certainly challenging at times.”

Dr. Eaton went on to become director for maternal health at the Ohio Department of Health and later served as president for the AAP Ohio Chapter and as AAP president from 1990 to 1991.

Her most important achievement however, was being a strong voice for children, she said. “My biggest accomplishment, I hope, was standing up for children and speaking out for children and assuming leadership roles in organizations like AAP to underscore that important role as an advocate.”
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M13-982 trial in del(17p) CLL: High, durable response rates to venetoclax

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– Venetoclax monotherapy is associated with high and durable objective response rates in patients with del(17p) chronic lymphocytic leukemia (CLL), according to efficacy findings from the open-label M13-982 trial.

Additionally, a safety expansion of the pivotal phase 2 study showed that treatment was well tolerated, and assessment of minimal residual disease (MRD) status in the peripheral blood and bone marrow of study participants correlated with the 24-month progression-free survival estimate of 100% for patients with complete remission/complete remission with incomplete blood count recovery (CR/CRi), Stephan Stilgenbauer, MD, of the University of Ulm, Germany, and his colleagues reported in a poster at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.

Frontline Medical News
Dr. Stephan Stilgenbauer
Initial approval of venetoclax – a potent, highly selective, orally bioavailable, small-molecular inhibitor of BCL-2 – for del(17p) CLL was granted in 2016 based on an overall response rate of 79% and a complete remission rate of 7.5% in the 107 patients in M13-982, the investigators noted.

That response was maintained at 1 year in 85% of participants.

The current findings, which represent data through April 2017 for those 107 patients from the main cohort, as well as for 51 patients in the safety expansion study, show an overall response rate of 77%, with 20% CR/CRi.

The median time to first response was 1 month, and time to CR/CRi was 9.8 months, they said.

Estimates at 24 months for duration of response, progression-free survival, and overall survival were 66%, 54%, and 73%, respectively.

Additionally, objective responses were seen in four of five previously untreated patients who were enrolled in the safety expansion, and two of them had complete remissions. One patient with best response of stable disease decided to discontinue treatment but remained in follow-up with stable disease.

“All patients were alive at the time of analysis and remain progression free,” the investigators wrote.

In 18 patients who received prior B-cell receptor pathway inhibitor (BCRi) therapy, the objective response rate was 61% and the complete remission rate was 11%, with 12-month, progression-free and overall survival estimates of 50% and 54%, respectively.

Treatment-emergent adverse events of any grade occurred in 98% of patients, and led to dosing interruption in 40% and dosing adjustment in 17%. The most common adverse event was neutropenia; grade 3/4 neutropenia occurred in 40% of patients.

Neutropenia lead to a dose reduction in 8% of patients and to treatment interruption in 6% of patients; no discontinuations were reported.

Infections occurred in 81% of 158 patients, and grade 3/4 infections occurred in 23%; these infections were consistent with the underlying disease, the investigators said.

Laboratory tumor lysis syndrome (TLS) occurred in 5% of patients, but there were no episodes of clinical TLS, they said, noting that five TLS patients required dose interruptions. TLS occurred in four patients with medium risk at screening and in four with high risk. All episodes of TLS occurred during initial dosing or ramp-up, and all resolved. Affected patients were able to resume venetoclax with dose escalation to 400 mg/day.

The rate of minimal residual disease negativity was 30% in the intention-to-treat population as demonstrated by flow cytometry and confirmed by next generation sequencing (NGS) in 21 of 29 patients with an evaluable matched time point specimen. Bone marrow MRD negativity was observed in 20 patients by flow cytometry, and in 9 patients by NGS.

When looking at flow cytometry and NGS data combined, the MRD negativity rate in peripheral blood was 25% overall and 40% in evaluable patients, and the MRD negativity rate in bone marrow was 11% overall and 24% in evaluable patients.

Of those who achieved CR/CRi, 69% were MRD negative in peripheral blood by flow cytometry, with a 24-month, progression-free survival estimate of 100%, and 13 of those had confirmed MRD-negative blood by NGS, 2 had MRD-positive blood by NGS at a matched flow cytometry assessment, and 7 were not evaluated by NGS. For the remaining CR/CRi patients, who were MRD-positive by flow cytometry, the 24-month progression-free survival estimate was 86%.

Study participants in the main cohort were adults with a median age of 67 years who had relapsed/refractory CLL with an indication for treatment by iwCLL criteria, del(17p), good performance status, adequate bone marrow function, and creatinine clearance of at least 50 mg/min. They received a single test dose of 20 mg on day 1, with gradual ramp up to 400 mg over 4-5 weeks based on laboratory assessments. All were hospitalized for the first 20 mg and 50 mg venetoclax doses during ramp up.

Those in the safety expansion were treated with once-daily oral venetoclax starting at a dose of 20 mg/day for 1 week and ramped up to 400 mg by week 5. To mitigate TLS risk, uric acid–lowering agents and hydration were started at least 72 hours prior to administering the first dose. Those with high TLS risk – and some with medium risk – were hospitalized for the first 20-mg and 50-mg doses. Those with low TLS risk – and most with medium risk – received initial venetoclax dosing in an outpatient setting.

“Continued follow-up of patients in this trial will provide additional data on the durability of response with venetoclax in patients with del(17p) CLL,” the investigators wrote.

This study was supported by AbbVie and Genentech. Dr. Stilgenbauer received research funding, honoraria, and travel support from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Gilead, GSK, Janssen, Mundipharma, Novartis, Pharmacyclics, Hoffmann La-Roche, and Sanofi.
 

 

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– Venetoclax monotherapy is associated with high and durable objective response rates in patients with del(17p) chronic lymphocytic leukemia (CLL), according to efficacy findings from the open-label M13-982 trial.

Additionally, a safety expansion of the pivotal phase 2 study showed that treatment was well tolerated, and assessment of minimal residual disease (MRD) status in the peripheral blood and bone marrow of study participants correlated with the 24-month progression-free survival estimate of 100% for patients with complete remission/complete remission with incomplete blood count recovery (CR/CRi), Stephan Stilgenbauer, MD, of the University of Ulm, Germany, and his colleagues reported in a poster at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.

Frontline Medical News
Dr. Stephan Stilgenbauer
Initial approval of venetoclax – a potent, highly selective, orally bioavailable, small-molecular inhibitor of BCL-2 – for del(17p) CLL was granted in 2016 based on an overall response rate of 79% and a complete remission rate of 7.5% in the 107 patients in M13-982, the investigators noted.

That response was maintained at 1 year in 85% of participants.

The current findings, which represent data through April 2017 for those 107 patients from the main cohort, as well as for 51 patients in the safety expansion study, show an overall response rate of 77%, with 20% CR/CRi.

The median time to first response was 1 month, and time to CR/CRi was 9.8 months, they said.

Estimates at 24 months for duration of response, progression-free survival, and overall survival were 66%, 54%, and 73%, respectively.

Additionally, objective responses were seen in four of five previously untreated patients who were enrolled in the safety expansion, and two of them had complete remissions. One patient with best response of stable disease decided to discontinue treatment but remained in follow-up with stable disease.

“All patients were alive at the time of analysis and remain progression free,” the investigators wrote.

In 18 patients who received prior B-cell receptor pathway inhibitor (BCRi) therapy, the objective response rate was 61% and the complete remission rate was 11%, with 12-month, progression-free and overall survival estimates of 50% and 54%, respectively.

Treatment-emergent adverse events of any grade occurred in 98% of patients, and led to dosing interruption in 40% and dosing adjustment in 17%. The most common adverse event was neutropenia; grade 3/4 neutropenia occurred in 40% of patients.

Neutropenia lead to a dose reduction in 8% of patients and to treatment interruption in 6% of patients; no discontinuations were reported.

Infections occurred in 81% of 158 patients, and grade 3/4 infections occurred in 23%; these infections were consistent with the underlying disease, the investigators said.

Laboratory tumor lysis syndrome (TLS) occurred in 5% of patients, but there were no episodes of clinical TLS, they said, noting that five TLS patients required dose interruptions. TLS occurred in four patients with medium risk at screening and in four with high risk. All episodes of TLS occurred during initial dosing or ramp-up, and all resolved. Affected patients were able to resume venetoclax with dose escalation to 400 mg/day.

The rate of minimal residual disease negativity was 30% in the intention-to-treat population as demonstrated by flow cytometry and confirmed by next generation sequencing (NGS) in 21 of 29 patients with an evaluable matched time point specimen. Bone marrow MRD negativity was observed in 20 patients by flow cytometry, and in 9 patients by NGS.

When looking at flow cytometry and NGS data combined, the MRD negativity rate in peripheral blood was 25% overall and 40% in evaluable patients, and the MRD negativity rate in bone marrow was 11% overall and 24% in evaluable patients.

Of those who achieved CR/CRi, 69% were MRD negative in peripheral blood by flow cytometry, with a 24-month, progression-free survival estimate of 100%, and 13 of those had confirmed MRD-negative blood by NGS, 2 had MRD-positive blood by NGS at a matched flow cytometry assessment, and 7 were not evaluated by NGS. For the remaining CR/CRi patients, who were MRD-positive by flow cytometry, the 24-month progression-free survival estimate was 86%.

Study participants in the main cohort were adults with a median age of 67 years who had relapsed/refractory CLL with an indication for treatment by iwCLL criteria, del(17p), good performance status, adequate bone marrow function, and creatinine clearance of at least 50 mg/min. They received a single test dose of 20 mg on day 1, with gradual ramp up to 400 mg over 4-5 weeks based on laboratory assessments. All were hospitalized for the first 20 mg and 50 mg venetoclax doses during ramp up.

Those in the safety expansion were treated with once-daily oral venetoclax starting at a dose of 20 mg/day for 1 week and ramped up to 400 mg by week 5. To mitigate TLS risk, uric acid–lowering agents and hydration were started at least 72 hours prior to administering the first dose. Those with high TLS risk – and some with medium risk – were hospitalized for the first 20-mg and 50-mg doses. Those with low TLS risk – and most with medium risk – received initial venetoclax dosing in an outpatient setting.

“Continued follow-up of patients in this trial will provide additional data on the durability of response with venetoclax in patients with del(17p) CLL,” the investigators wrote.

This study was supported by AbbVie and Genentech. Dr. Stilgenbauer received research funding, honoraria, and travel support from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Gilead, GSK, Janssen, Mundipharma, Novartis, Pharmacyclics, Hoffmann La-Roche, and Sanofi.
 

 

 

– Venetoclax monotherapy is associated with high and durable objective response rates in patients with del(17p) chronic lymphocytic leukemia (CLL), according to efficacy findings from the open-label M13-982 trial.

Additionally, a safety expansion of the pivotal phase 2 study showed that treatment was well tolerated, and assessment of minimal residual disease (MRD) status in the peripheral blood and bone marrow of study participants correlated with the 24-month progression-free survival estimate of 100% for patients with complete remission/complete remission with incomplete blood count recovery (CR/CRi), Stephan Stilgenbauer, MD, of the University of Ulm, Germany, and his colleagues reported in a poster at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.

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Dr. Stephan Stilgenbauer
Initial approval of venetoclax – a potent, highly selective, orally bioavailable, small-molecular inhibitor of BCL-2 – for del(17p) CLL was granted in 2016 based on an overall response rate of 79% and a complete remission rate of 7.5% in the 107 patients in M13-982, the investigators noted.

That response was maintained at 1 year in 85% of participants.

The current findings, which represent data through April 2017 for those 107 patients from the main cohort, as well as for 51 patients in the safety expansion study, show an overall response rate of 77%, with 20% CR/CRi.

The median time to first response was 1 month, and time to CR/CRi was 9.8 months, they said.

Estimates at 24 months for duration of response, progression-free survival, and overall survival were 66%, 54%, and 73%, respectively.

Additionally, objective responses were seen in four of five previously untreated patients who were enrolled in the safety expansion, and two of them had complete remissions. One patient with best response of stable disease decided to discontinue treatment but remained in follow-up with stable disease.

“All patients were alive at the time of analysis and remain progression free,” the investigators wrote.

In 18 patients who received prior B-cell receptor pathway inhibitor (BCRi) therapy, the objective response rate was 61% and the complete remission rate was 11%, with 12-month, progression-free and overall survival estimates of 50% and 54%, respectively.

Treatment-emergent adverse events of any grade occurred in 98% of patients, and led to dosing interruption in 40% and dosing adjustment in 17%. The most common adverse event was neutropenia; grade 3/4 neutropenia occurred in 40% of patients.

Neutropenia lead to a dose reduction in 8% of patients and to treatment interruption in 6% of patients; no discontinuations were reported.

Infections occurred in 81% of 158 patients, and grade 3/4 infections occurred in 23%; these infections were consistent with the underlying disease, the investigators said.

Laboratory tumor lysis syndrome (TLS) occurred in 5% of patients, but there were no episodes of clinical TLS, they said, noting that five TLS patients required dose interruptions. TLS occurred in four patients with medium risk at screening and in four with high risk. All episodes of TLS occurred during initial dosing or ramp-up, and all resolved. Affected patients were able to resume venetoclax with dose escalation to 400 mg/day.

The rate of minimal residual disease negativity was 30% in the intention-to-treat population as demonstrated by flow cytometry and confirmed by next generation sequencing (NGS) in 21 of 29 patients with an evaluable matched time point specimen. Bone marrow MRD negativity was observed in 20 patients by flow cytometry, and in 9 patients by NGS.

When looking at flow cytometry and NGS data combined, the MRD negativity rate in peripheral blood was 25% overall and 40% in evaluable patients, and the MRD negativity rate in bone marrow was 11% overall and 24% in evaluable patients.

Of those who achieved CR/CRi, 69% were MRD negative in peripheral blood by flow cytometry, with a 24-month, progression-free survival estimate of 100%, and 13 of those had confirmed MRD-negative blood by NGS, 2 had MRD-positive blood by NGS at a matched flow cytometry assessment, and 7 were not evaluated by NGS. For the remaining CR/CRi patients, who were MRD-positive by flow cytometry, the 24-month progression-free survival estimate was 86%.

Study participants in the main cohort were adults with a median age of 67 years who had relapsed/refractory CLL with an indication for treatment by iwCLL criteria, del(17p), good performance status, adequate bone marrow function, and creatinine clearance of at least 50 mg/min. They received a single test dose of 20 mg on day 1, with gradual ramp up to 400 mg over 4-5 weeks based on laboratory assessments. All were hospitalized for the first 20 mg and 50 mg venetoclax doses during ramp up.

Those in the safety expansion were treated with once-daily oral venetoclax starting at a dose of 20 mg/day for 1 week and ramped up to 400 mg by week 5. To mitigate TLS risk, uric acid–lowering agents and hydration were started at least 72 hours prior to administering the first dose. Those with high TLS risk – and some with medium risk – were hospitalized for the first 20-mg and 50-mg doses. Those with low TLS risk – and most with medium risk – received initial venetoclax dosing in an outpatient setting.

“Continued follow-up of patients in this trial will provide additional data on the durability of response with venetoclax in patients with del(17p) CLL,” the investigators wrote.

This study was supported by AbbVie and Genentech. Dr. Stilgenbauer received research funding, honoraria, and travel support from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Gilead, GSK, Janssen, Mundipharma, Novartis, Pharmacyclics, Hoffmann La-Roche, and Sanofi.
 

 

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Key clinical point: Venetoclax monotherapy is well tolerated and associated with high and durable objective response rates in patients with del(17p) CLL.

Major finding: At April 2017 data analysis, the overall response rate was 77% with 20% CR/CRi.

Data source: The phase 2 open-label M13-982 Trial and safety expansion cohort of 158 total patients.

Disclosures: This study was supported by AbbVie and Genentech. Dr. Stilgenbauer received research funding, honoraria, and travel support from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Gilead, GSK, Janssen, Mundipharma, Novartis, Pharmacyclics, Hoffmann La-Roche, and Sanofi.

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Multiple factors predict surgical site infection risk after lower extremity revascularization

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Patient, operative, and hospital factors were found to be significant predictors of the risk of surgical site infection in patients who underwent open lower extremity bypass procedures, according to the results of a retrospective data analysis.

The study assessed the outcomes of 3,033 patients who underwent elective or urgent open LEB procedures between January 2012 and June 2015 using data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Vascular Intervention Collaborative (BMC2 VIC), a statewide cardiovascular consortium of 35 hospitals, according to Frank M. Davis, MD, and his colleagues at the University of Michigan, Ann Arbor.

Demographic information, medical history, laboratory test results before and after the procedure, procedural indication, procedural urgency, technical details of procedures, and associated complications were assessed for each patient. Women comprised 31% of patients, the average patient age was 66 years, and 83% of the population was white (J Vasc Surg. 2017 Jun;65[6]:1769-78).

Among all of the patients treated, 320 developed SSIs and 2,713 did not. The procedural indications included one or more of the following: claudication (72%), rest pain (50.5%), ulcer/gangrene (32.4%), or acute limb ischemia (15.1%). Antibiotics were appropriately administered to 97% of the patients, according to the researchers, “demonstrating high compliance across the BMC2 VIC.”

  • Patient factors: As indicated by previous studies, obesity (odds ratio, 1.78), dialysis dependence (OR, 4.33), and hypertension (OR, 4.29) conferred a significant increased risk of SSI after LEB, according to Dr. Davis and his colleagues. In addition, however, they found that previous vascular surgery (OR, 1.57), previous percutaneous coronary intervention (OR, 1.47), use of antiplatelet medication (OR, 4.29), and low Peripheral Artery Questionnaire symptom severity (OR, 1.48) were significant independent predictors of SSI.
  • Operative factors: Prolonged procedural length (OR, 2.95), iodine-only antiseptic skin preparation (OR, 1.73), and high peak intraoperative glucose (defined as a peak glucose greater than 180 mg/dL; OR, 1.99) were significant independent predictors of SSI. However, concomitant stent placement was found to be significantly predictive (OR, .38), “perhaps due to improvement in regional and subcutaneous vascular flow after the intervention,” the researchers suggested.
  • Hospital factors: Larger overall hospital size (OR, 2.22) and major teaching center (OR, 1.66) were associated with increased risk of SSI. “Interestingly, we did not find an association with SSI and the hospital annual volume or the hospital urgent/emergent procedure rate,” the researchers added.

SSIs were not found to be significantly associated with a difference in 30-day mortality. However, they were significantly associated with an increased rate of several postoperative morbidities, including transfusion, lymph leak, major amputation, and open surgical bypass revision at or within 30 days of the index operation, according to Dr. Davis and his colleagues.

“Although some factors, such as patients comorbidities, are not modifiable, others represent areas for quality improvement in at-risk patients,” the researchers indicated. “Diligence should be devoted to decreasing operative length, controlling intraoperative glucose levels, and avoiding iodine-only skin preparation to decrease the rate of SSIs and its numerous associate morbidities in vascular surgery patients.”

In discussing the issue of antiplatelet medication being an indicator of increased risk, the authors pointed out that it was a hitherto unreported factor in the vascular literature, and of concern because, “as expected, a high percentage of patients (78.7%) were taking antiplatelet medication at the time of their LEB.”

Because the association of antiplatelet medication with SSIs was independent of the need for operative transfusion or the need for repeat intervention, the researchers speculated that “all antiplatelet agents have the theoretical potential to diminish activation-dependent platelet immune functions.” They referred to previous studies showing that clopidogrel was associated with significantly higher clinical rates of infection, particularly pneumonia.

Limitations cited for the study were the retrospective nature of the database analysis, the possibility of confounders not assessed in the data, and the fact that outcomes were limited to 30-day events, which would not take into account longer-term graft failure or mortality.

The authors reported having no conflicts of interest with regard to the study.

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Patient, operative, and hospital factors were found to be significant predictors of the risk of surgical site infection in patients who underwent open lower extremity bypass procedures, according to the results of a retrospective data analysis.

The study assessed the outcomes of 3,033 patients who underwent elective or urgent open LEB procedures between January 2012 and June 2015 using data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Vascular Intervention Collaborative (BMC2 VIC), a statewide cardiovascular consortium of 35 hospitals, according to Frank M. Davis, MD, and his colleagues at the University of Michigan, Ann Arbor.

Demographic information, medical history, laboratory test results before and after the procedure, procedural indication, procedural urgency, technical details of procedures, and associated complications were assessed for each patient. Women comprised 31% of patients, the average patient age was 66 years, and 83% of the population was white (J Vasc Surg. 2017 Jun;65[6]:1769-78).

Among all of the patients treated, 320 developed SSIs and 2,713 did not. The procedural indications included one or more of the following: claudication (72%), rest pain (50.5%), ulcer/gangrene (32.4%), or acute limb ischemia (15.1%). Antibiotics were appropriately administered to 97% of the patients, according to the researchers, “demonstrating high compliance across the BMC2 VIC.”

  • Patient factors: As indicated by previous studies, obesity (odds ratio, 1.78), dialysis dependence (OR, 4.33), and hypertension (OR, 4.29) conferred a significant increased risk of SSI after LEB, according to Dr. Davis and his colleagues. In addition, however, they found that previous vascular surgery (OR, 1.57), previous percutaneous coronary intervention (OR, 1.47), use of antiplatelet medication (OR, 4.29), and low Peripheral Artery Questionnaire symptom severity (OR, 1.48) were significant independent predictors of SSI.
  • Operative factors: Prolonged procedural length (OR, 2.95), iodine-only antiseptic skin preparation (OR, 1.73), and high peak intraoperative glucose (defined as a peak glucose greater than 180 mg/dL; OR, 1.99) were significant independent predictors of SSI. However, concomitant stent placement was found to be significantly predictive (OR, .38), “perhaps due to improvement in regional and subcutaneous vascular flow after the intervention,” the researchers suggested.
  • Hospital factors: Larger overall hospital size (OR, 2.22) and major teaching center (OR, 1.66) were associated with increased risk of SSI. “Interestingly, we did not find an association with SSI and the hospital annual volume or the hospital urgent/emergent procedure rate,” the researchers added.

SSIs were not found to be significantly associated with a difference in 30-day mortality. However, they were significantly associated with an increased rate of several postoperative morbidities, including transfusion, lymph leak, major amputation, and open surgical bypass revision at or within 30 days of the index operation, according to Dr. Davis and his colleagues.

“Although some factors, such as patients comorbidities, are not modifiable, others represent areas for quality improvement in at-risk patients,” the researchers indicated. “Diligence should be devoted to decreasing operative length, controlling intraoperative glucose levels, and avoiding iodine-only skin preparation to decrease the rate of SSIs and its numerous associate morbidities in vascular surgery patients.”

In discussing the issue of antiplatelet medication being an indicator of increased risk, the authors pointed out that it was a hitherto unreported factor in the vascular literature, and of concern because, “as expected, a high percentage of patients (78.7%) were taking antiplatelet medication at the time of their LEB.”

Because the association of antiplatelet medication with SSIs was independent of the need for operative transfusion or the need for repeat intervention, the researchers speculated that “all antiplatelet agents have the theoretical potential to diminish activation-dependent platelet immune functions.” They referred to previous studies showing that clopidogrel was associated with significantly higher clinical rates of infection, particularly pneumonia.

Limitations cited for the study were the retrospective nature of the database analysis, the possibility of confounders not assessed in the data, and the fact that outcomes were limited to 30-day events, which would not take into account longer-term graft failure or mortality.

The authors reported having no conflicts of interest with regard to the study.

 

Patient, operative, and hospital factors were found to be significant predictors of the risk of surgical site infection in patients who underwent open lower extremity bypass procedures, according to the results of a retrospective data analysis.

The study assessed the outcomes of 3,033 patients who underwent elective or urgent open LEB procedures between January 2012 and June 2015 using data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Vascular Intervention Collaborative (BMC2 VIC), a statewide cardiovascular consortium of 35 hospitals, according to Frank M. Davis, MD, and his colleagues at the University of Michigan, Ann Arbor.

Demographic information, medical history, laboratory test results before and after the procedure, procedural indication, procedural urgency, technical details of procedures, and associated complications were assessed for each patient. Women comprised 31% of patients, the average patient age was 66 years, and 83% of the population was white (J Vasc Surg. 2017 Jun;65[6]:1769-78).

Among all of the patients treated, 320 developed SSIs and 2,713 did not. The procedural indications included one or more of the following: claudication (72%), rest pain (50.5%), ulcer/gangrene (32.4%), or acute limb ischemia (15.1%). Antibiotics were appropriately administered to 97% of the patients, according to the researchers, “demonstrating high compliance across the BMC2 VIC.”

  • Patient factors: As indicated by previous studies, obesity (odds ratio, 1.78), dialysis dependence (OR, 4.33), and hypertension (OR, 4.29) conferred a significant increased risk of SSI after LEB, according to Dr. Davis and his colleagues. In addition, however, they found that previous vascular surgery (OR, 1.57), previous percutaneous coronary intervention (OR, 1.47), use of antiplatelet medication (OR, 4.29), and low Peripheral Artery Questionnaire symptom severity (OR, 1.48) were significant independent predictors of SSI.
  • Operative factors: Prolonged procedural length (OR, 2.95), iodine-only antiseptic skin preparation (OR, 1.73), and high peak intraoperative glucose (defined as a peak glucose greater than 180 mg/dL; OR, 1.99) were significant independent predictors of SSI. However, concomitant stent placement was found to be significantly predictive (OR, .38), “perhaps due to improvement in regional and subcutaneous vascular flow after the intervention,” the researchers suggested.
  • Hospital factors: Larger overall hospital size (OR, 2.22) and major teaching center (OR, 1.66) were associated with increased risk of SSI. “Interestingly, we did not find an association with SSI and the hospital annual volume or the hospital urgent/emergent procedure rate,” the researchers added.

SSIs were not found to be significantly associated with a difference in 30-day mortality. However, they were significantly associated with an increased rate of several postoperative morbidities, including transfusion, lymph leak, major amputation, and open surgical bypass revision at or within 30 days of the index operation, according to Dr. Davis and his colleagues.

“Although some factors, such as patients comorbidities, are not modifiable, others represent areas for quality improvement in at-risk patients,” the researchers indicated. “Diligence should be devoted to decreasing operative length, controlling intraoperative glucose levels, and avoiding iodine-only skin preparation to decrease the rate of SSIs and its numerous associate morbidities in vascular surgery patients.”

In discussing the issue of antiplatelet medication being an indicator of increased risk, the authors pointed out that it was a hitherto unreported factor in the vascular literature, and of concern because, “as expected, a high percentage of patients (78.7%) were taking antiplatelet medication at the time of their LEB.”

Because the association of antiplatelet medication with SSIs was independent of the need for operative transfusion or the need for repeat intervention, the researchers speculated that “all antiplatelet agents have the theoretical potential to diminish activation-dependent platelet immune functions.” They referred to previous studies showing that clopidogrel was associated with significantly higher clinical rates of infection, particularly pneumonia.

Limitations cited for the study were the retrospective nature of the database analysis, the possibility of confounders not assessed in the data, and the fact that outcomes were limited to 30-day events, which would not take into account longer-term graft failure or mortality.

The authors reported having no conflicts of interest with regard to the study.

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FROM THE JOURNAL OF VASCULAR SURGERY

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Key clinical point: Procedural length, preoperative antiplatelet medication, peak intraoperative glucose, and iodine-based skin preparation were among the factors that increased the risk of SSIs.

Major finding: SSIs occurred in 10.6% of lower extremity bypasses.

Data source: A retrospective analysis of 3,033 elective or urgent open LEB procedures performed over a 3.5-year period in a statewide cardiovascular consortium of 35 hospitals.

Disclosures: The authors reported having no conflicts of interest with regard to the study.

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Better bariatric surgery outcomes with lower preoperative BMI

Results confirm benefits of BMI below 30 after bariatric surgery
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Delaying bariatric surgery until body mass index is highly elevated may reduce the likelihood of achieving a BMI of less than 30 within a year, according to a paper published online July 26 in JAMA Surgery.

A retrospective study using prospectively gathered clinical data of 27,320 adults who underwent bariatric surgery in Michigan showed around one in three (36%) achieved a BMI below 30 within a year after surgery (JAMA Surgery 2017, July 26. doi: 10.1001/jamasurg.2017.2348). But obese patients with a body mass index of less than 40 kg/m2 before undergoing bariatric surgery are significantly more likely to achieve a postoperative BMI of under 30.

Individuals who had a preoperative BMI of less than 40 had a 12-fold higher chance of getting their BMI below 30, compared to those whose preoperative BMI was 40 or above (95% confidence interval 1.71-14.16, P less than .001). Only 8.5% of individuals with a BMI at or above 50 achieved a postoperative BMI below 30.

Dr. Oliver A. Varban
“It is important to note that EWL [excess weight loss] percentage may appear exaggerated in relation to actual mass lost in patients with lower initial BMI in these studies,” wrote Oliver A. Varban, MD, FACS, of the University of Michigan Health Systems, and his coauthors. “However, it also highlights the advantages of early surgical management of obesity in that smaller amounts of weight loss are required to achieve the desired effect.”

The likelihood of getting below 30 within a year was eightfold higher in patients who had a sleeve gastrectomy, 21 times greater in those who underwent Roux-en-Y bypass, and 82 times higher in those who had a duodenal switch, compared with patients who had adjustable gastric banding (P less than .001).

The researchers also compared other outcomes in individuals whose BMI dropped below 30 and in those who did not achieve this degree of weight loss. The analysis showed that those with a BMI below 30 after 1 year had at least a twofold greater chance of discontinuing cholesterol-lowering medications, insulin, diabetes medications, antihypertensives, and CPAP for sleep apnea, compared with those whose BMI remained at 30 or above. They were also more than three times more likely to report being ‘very satisfied’ with the outcomes of surgery.

The authors noted that the cohort’s mean BMI was 48, which was above the established threshold for bariatric surgery, namely a BMI of 40, or 35 with weight-related comorbidities.

“Our results suggest that patients with morbid obesity should be targeted for surgery when their BMI is still less than 40, as these patients are more likely to achieve a target BMI that results in substantial reduction in weight-related comorbidities,” the authors wrote.

However, they stressed that their findings should not be taken as a reason to exclude patients with a BMI above 40 from surgery, pointing out that even for patients with higher preoperative BMIs, bariatric surgery offered substantial health and quality of life benefits.

They also acknowledged that 1-year weight data was available for around 50% of patients in the registry, which may have led to selection bias.

“Policies and practice patterns that delay or incentivize patients to pursue bariatric surgery only once the BMI is highly elevated can result in inferior outcomes,” the investigators concluded.

Blue Cross Blue Shield of Michigan/Blue Care Network funded the study. Three authors had received salary support from Blue Cross Blue Shield. No other conflicts of interest were declared.
Body

 

The authors’ conclusion that bariatric surgery should be more liberally applied to patients with less severe obesity is consistent with multiple reports of improved control of type 2 diabetes, if not remission, among lower-BMI patient populations following MBS [metabolic and bariatric surgery]. However, these reports generally do not refute the importance of weight loss in achieving important clinical benefit among patients with obesity-related comorbid disease.

One strength of the present study is that it is a clinical database. However, 50% attrition of the follow-up weight loss data at 1 year is potentially problematic.
 

Bruce M. Wolfe, MD, FACS, and Elizaveta Walker, MPH, are in the division of bariatric surgery, department of surgery, at Oregon Health & Science University, Portland. These comments are taken from an accompanying editorial (JAMA Surgery 2017 Jul 26. doi: 10.1001/jamasurg.2017.2349). No conflicts of interest were declared.

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Body

 

The authors’ conclusion that bariatric surgery should be more liberally applied to patients with less severe obesity is consistent with multiple reports of improved control of type 2 diabetes, if not remission, among lower-BMI patient populations following MBS [metabolic and bariatric surgery]. However, these reports generally do not refute the importance of weight loss in achieving important clinical benefit among patients with obesity-related comorbid disease.

One strength of the present study is that it is a clinical database. However, 50% attrition of the follow-up weight loss data at 1 year is potentially problematic.
 

Bruce M. Wolfe, MD, FACS, and Elizaveta Walker, MPH, are in the division of bariatric surgery, department of surgery, at Oregon Health & Science University, Portland. These comments are taken from an accompanying editorial (JAMA Surgery 2017 Jul 26. doi: 10.1001/jamasurg.2017.2349). No conflicts of interest were declared.

Body

 

The authors’ conclusion that bariatric surgery should be more liberally applied to patients with less severe obesity is consistent with multiple reports of improved control of type 2 diabetes, if not remission, among lower-BMI patient populations following MBS [metabolic and bariatric surgery]. However, these reports generally do not refute the importance of weight loss in achieving important clinical benefit among patients with obesity-related comorbid disease.

One strength of the present study is that it is a clinical database. However, 50% attrition of the follow-up weight loss data at 1 year is potentially problematic.
 

Bruce M. Wolfe, MD, FACS, and Elizaveta Walker, MPH, are in the division of bariatric surgery, department of surgery, at Oregon Health & Science University, Portland. These comments are taken from an accompanying editorial (JAMA Surgery 2017 Jul 26. doi: 10.1001/jamasurg.2017.2349). No conflicts of interest were declared.

Title
Results confirm benefits of BMI below 30 after bariatric surgery
Results confirm benefits of BMI below 30 after bariatric surgery

 

Delaying bariatric surgery until body mass index is highly elevated may reduce the likelihood of achieving a BMI of less than 30 within a year, according to a paper published online July 26 in JAMA Surgery.

A retrospective study using prospectively gathered clinical data of 27,320 adults who underwent bariatric surgery in Michigan showed around one in three (36%) achieved a BMI below 30 within a year after surgery (JAMA Surgery 2017, July 26. doi: 10.1001/jamasurg.2017.2348). But obese patients with a body mass index of less than 40 kg/m2 before undergoing bariatric surgery are significantly more likely to achieve a postoperative BMI of under 30.

Individuals who had a preoperative BMI of less than 40 had a 12-fold higher chance of getting their BMI below 30, compared to those whose preoperative BMI was 40 or above (95% confidence interval 1.71-14.16, P less than .001). Only 8.5% of individuals with a BMI at or above 50 achieved a postoperative BMI below 30.

Dr. Oliver A. Varban
“It is important to note that EWL [excess weight loss] percentage may appear exaggerated in relation to actual mass lost in patients with lower initial BMI in these studies,” wrote Oliver A. Varban, MD, FACS, of the University of Michigan Health Systems, and his coauthors. “However, it also highlights the advantages of early surgical management of obesity in that smaller amounts of weight loss are required to achieve the desired effect.”

The likelihood of getting below 30 within a year was eightfold higher in patients who had a sleeve gastrectomy, 21 times greater in those who underwent Roux-en-Y bypass, and 82 times higher in those who had a duodenal switch, compared with patients who had adjustable gastric banding (P less than .001).

The researchers also compared other outcomes in individuals whose BMI dropped below 30 and in those who did not achieve this degree of weight loss. The analysis showed that those with a BMI below 30 after 1 year had at least a twofold greater chance of discontinuing cholesterol-lowering medications, insulin, diabetes medications, antihypertensives, and CPAP for sleep apnea, compared with those whose BMI remained at 30 or above. They were also more than three times more likely to report being ‘very satisfied’ with the outcomes of surgery.

The authors noted that the cohort’s mean BMI was 48, which was above the established threshold for bariatric surgery, namely a BMI of 40, or 35 with weight-related comorbidities.

“Our results suggest that patients with morbid obesity should be targeted for surgery when their BMI is still less than 40, as these patients are more likely to achieve a target BMI that results in substantial reduction in weight-related comorbidities,” the authors wrote.

However, they stressed that their findings should not be taken as a reason to exclude patients with a BMI above 40 from surgery, pointing out that even for patients with higher preoperative BMIs, bariatric surgery offered substantial health and quality of life benefits.

They also acknowledged that 1-year weight data was available for around 50% of patients in the registry, which may have led to selection bias.

“Policies and practice patterns that delay or incentivize patients to pursue bariatric surgery only once the BMI is highly elevated can result in inferior outcomes,” the investigators concluded.

Blue Cross Blue Shield of Michigan/Blue Care Network funded the study. Three authors had received salary support from Blue Cross Blue Shield. No other conflicts of interest were declared.

 

Delaying bariatric surgery until body mass index is highly elevated may reduce the likelihood of achieving a BMI of less than 30 within a year, according to a paper published online July 26 in JAMA Surgery.

A retrospective study using prospectively gathered clinical data of 27,320 adults who underwent bariatric surgery in Michigan showed around one in three (36%) achieved a BMI below 30 within a year after surgery (JAMA Surgery 2017, July 26. doi: 10.1001/jamasurg.2017.2348). But obese patients with a body mass index of less than 40 kg/m2 before undergoing bariatric surgery are significantly more likely to achieve a postoperative BMI of under 30.

Individuals who had a preoperative BMI of less than 40 had a 12-fold higher chance of getting their BMI below 30, compared to those whose preoperative BMI was 40 or above (95% confidence interval 1.71-14.16, P less than .001). Only 8.5% of individuals with a BMI at or above 50 achieved a postoperative BMI below 30.

Dr. Oliver A. Varban
“It is important to note that EWL [excess weight loss] percentage may appear exaggerated in relation to actual mass lost in patients with lower initial BMI in these studies,” wrote Oliver A. Varban, MD, FACS, of the University of Michigan Health Systems, and his coauthors. “However, it also highlights the advantages of early surgical management of obesity in that smaller amounts of weight loss are required to achieve the desired effect.”

The likelihood of getting below 30 within a year was eightfold higher in patients who had a sleeve gastrectomy, 21 times greater in those who underwent Roux-en-Y bypass, and 82 times higher in those who had a duodenal switch, compared with patients who had adjustable gastric banding (P less than .001).

The researchers also compared other outcomes in individuals whose BMI dropped below 30 and in those who did not achieve this degree of weight loss. The analysis showed that those with a BMI below 30 after 1 year had at least a twofold greater chance of discontinuing cholesterol-lowering medications, insulin, diabetes medications, antihypertensives, and CPAP for sleep apnea, compared with those whose BMI remained at 30 or above. They were also more than three times more likely to report being ‘very satisfied’ with the outcomes of surgery.

The authors noted that the cohort’s mean BMI was 48, which was above the established threshold for bariatric surgery, namely a BMI of 40, or 35 with weight-related comorbidities.

“Our results suggest that patients with morbid obesity should be targeted for surgery when their BMI is still less than 40, as these patients are more likely to achieve a target BMI that results in substantial reduction in weight-related comorbidities,” the authors wrote.

However, they stressed that their findings should not be taken as a reason to exclude patients with a BMI above 40 from surgery, pointing out that even for patients with higher preoperative BMIs, bariatric surgery offered substantial health and quality of life benefits.

They also acknowledged that 1-year weight data was available for around 50% of patients in the registry, which may have led to selection bias.

“Policies and practice patterns that delay or incentivize patients to pursue bariatric surgery only once the BMI is highly elevated can result in inferior outcomes,” the investigators concluded.

Blue Cross Blue Shield of Michigan/Blue Care Network funded the study. Three authors had received salary support from Blue Cross Blue Shield. No other conflicts of interest were declared.
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Key clinical point: A BMI below 40 prior to undergoing bariatric surgery gives patients a significantly better chance of achieving a 1-year postoperative BMI under 30.

Major finding: Obese patients with a BMI less than 40 before undergoing bariatric surgery are more than 12 times more likely to achieve a postoperative BMI of under 30.

Data source: A retrospective study using prospectively gathered clinical data of 27, 320 adults who underwent bariatric surgery.

Disclosures: Blue Cross Blue Shield of Michigan/Blue Care Network funded the study. Three authors had received salary support from Blue Cross Blue Shield. No other conflicts of interest were declared.

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First Senate vote to repeal and replace ACA fails

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Senate Republicans’ first attempt to repeal and replace the Affordable Care Act failed July 25 as nine Republican senators crossed the aisle to vote against a measure that had no chance of passing.

The process started with a dramatic appearance by Sen. John McCain (R-Ariz.), recovering from surgery to diagnose glioblastoma, who returned to Washington to cast a key vote that would allow debate to move forward. The Senate split 50-50 on that vote, with Sen. Susan Collins (R-Maine) and Sen. Lisa Murkowski (R-Alaska) crossing the aisle to vote with all the chamber’s Democrats against the motion to proceed. Vice President Mike Pence cast the tie-breaking vote in favor of beginning debate.

designer491/Thinkstock
The bill under consideration was the Obamacare Repeal Reconciliation Act, which aimed to repeal the ACA by the end of 2019.

However, the first amendment voted on would have replaced that language with the most recent version of the Senate GOP repeal-and-replace plan, the Better Care Reconciliation Act, with two additional provisions. One was from Sen. Ted Cruz (R-Tex.) and would allow insurers to offer more limited health insurance plans along side plans that cover the ACA’s essential benefits package. A second provision from Sen. Rob Portman (R-Ohio) would have added an additional $100 billion to the state stability fund to help low-income individuals whose Medicaid coverage was repealed.

The amendment was dead on arrival, as it would have needed 60 votes to pass. Throughout the repeal-and-replace effort, the 48 Senate Democrats have been firm in voting against any action. While much of the repeal-and-replace effort to date has relied on the budget reconciliation process, which requires a simple majority for passage, this legislation did not qualify and needed a supermajority of 60 votes for passage.

The nine GOP senators voting against the amendment included Collins, Murkowski, Bob Corker (Tenn.), Tom Cotton (Ark.), Lindsey Graham (S.C.), Dena Heller (Nev.), Mike Lee (Utah), Jerry Moran (Kan.), and Rand Paul (Ky.).

Earlier in the day, just after voting in favor of action on this legislation, Sen. McCain pleaded with his colleagues to return to regular order and write a bill that has bipartisan support. He criticized congressional Democrats for forcing the ACA through without bipartisan support 7 years ago and congressional Republicans for doing the exact same thing now with their repeal-and-replace efforts.

“Why don’t we try the old way of legislating in the Senate, the way our rules and customs encourage us to act,” Sen. McCain asked. “Let the Health, Education, Labor, and Pensions Committee under Chairman Alexander and Ranking Member Murray hold hearings, try to report a bill out of committee with contributions from both sides. Then bring it to the floor for amendment and debate and see if we can pass something that will be imperfect, full of compromises, and not very pleasing to implacable partisans on either side but that might provide workable solutions to problems Americans are struggling with today.”

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Senate Republicans’ first attempt to repeal and replace the Affordable Care Act failed July 25 as nine Republican senators crossed the aisle to vote against a measure that had no chance of passing.

The process started with a dramatic appearance by Sen. John McCain (R-Ariz.), recovering from surgery to diagnose glioblastoma, who returned to Washington to cast a key vote that would allow debate to move forward. The Senate split 50-50 on that vote, with Sen. Susan Collins (R-Maine) and Sen. Lisa Murkowski (R-Alaska) crossing the aisle to vote with all the chamber’s Democrats against the motion to proceed. Vice President Mike Pence cast the tie-breaking vote in favor of beginning debate.

designer491/Thinkstock
The bill under consideration was the Obamacare Repeal Reconciliation Act, which aimed to repeal the ACA by the end of 2019.

However, the first amendment voted on would have replaced that language with the most recent version of the Senate GOP repeal-and-replace plan, the Better Care Reconciliation Act, with two additional provisions. One was from Sen. Ted Cruz (R-Tex.) and would allow insurers to offer more limited health insurance plans along side plans that cover the ACA’s essential benefits package. A second provision from Sen. Rob Portman (R-Ohio) would have added an additional $100 billion to the state stability fund to help low-income individuals whose Medicaid coverage was repealed.

The amendment was dead on arrival, as it would have needed 60 votes to pass. Throughout the repeal-and-replace effort, the 48 Senate Democrats have been firm in voting against any action. While much of the repeal-and-replace effort to date has relied on the budget reconciliation process, which requires a simple majority for passage, this legislation did not qualify and needed a supermajority of 60 votes for passage.

The nine GOP senators voting against the amendment included Collins, Murkowski, Bob Corker (Tenn.), Tom Cotton (Ark.), Lindsey Graham (S.C.), Dena Heller (Nev.), Mike Lee (Utah), Jerry Moran (Kan.), and Rand Paul (Ky.).

Earlier in the day, just after voting in favor of action on this legislation, Sen. McCain pleaded with his colleagues to return to regular order and write a bill that has bipartisan support. He criticized congressional Democrats for forcing the ACA through without bipartisan support 7 years ago and congressional Republicans for doing the exact same thing now with their repeal-and-replace efforts.

“Why don’t we try the old way of legislating in the Senate, the way our rules and customs encourage us to act,” Sen. McCain asked. “Let the Health, Education, Labor, and Pensions Committee under Chairman Alexander and Ranking Member Murray hold hearings, try to report a bill out of committee with contributions from both sides. Then bring it to the floor for amendment and debate and see if we can pass something that will be imperfect, full of compromises, and not very pleasing to implacable partisans on either side but that might provide workable solutions to problems Americans are struggling with today.”

 

Senate Republicans’ first attempt to repeal and replace the Affordable Care Act failed July 25 as nine Republican senators crossed the aisle to vote against a measure that had no chance of passing.

The process started with a dramatic appearance by Sen. John McCain (R-Ariz.), recovering from surgery to diagnose glioblastoma, who returned to Washington to cast a key vote that would allow debate to move forward. The Senate split 50-50 on that vote, with Sen. Susan Collins (R-Maine) and Sen. Lisa Murkowski (R-Alaska) crossing the aisle to vote with all the chamber’s Democrats against the motion to proceed. Vice President Mike Pence cast the tie-breaking vote in favor of beginning debate.

designer491/Thinkstock
The bill under consideration was the Obamacare Repeal Reconciliation Act, which aimed to repeal the ACA by the end of 2019.

However, the first amendment voted on would have replaced that language with the most recent version of the Senate GOP repeal-and-replace plan, the Better Care Reconciliation Act, with two additional provisions. One was from Sen. Ted Cruz (R-Tex.) and would allow insurers to offer more limited health insurance plans along side plans that cover the ACA’s essential benefits package. A second provision from Sen. Rob Portman (R-Ohio) would have added an additional $100 billion to the state stability fund to help low-income individuals whose Medicaid coverage was repealed.

The amendment was dead on arrival, as it would have needed 60 votes to pass. Throughout the repeal-and-replace effort, the 48 Senate Democrats have been firm in voting against any action. While much of the repeal-and-replace effort to date has relied on the budget reconciliation process, which requires a simple majority for passage, this legislation did not qualify and needed a supermajority of 60 votes for passage.

The nine GOP senators voting against the amendment included Collins, Murkowski, Bob Corker (Tenn.), Tom Cotton (Ark.), Lindsey Graham (S.C.), Dena Heller (Nev.), Mike Lee (Utah), Jerry Moran (Kan.), and Rand Paul (Ky.).

Earlier in the day, just after voting in favor of action on this legislation, Sen. McCain pleaded with his colleagues to return to regular order and write a bill that has bipartisan support. He criticized congressional Democrats for forcing the ACA through without bipartisan support 7 years ago and congressional Republicans for doing the exact same thing now with their repeal-and-replace efforts.

“Why don’t we try the old way of legislating in the Senate, the way our rules and customs encourage us to act,” Sen. McCain asked. “Let the Health, Education, Labor, and Pensions Committee under Chairman Alexander and Ranking Member Murray hold hearings, try to report a bill out of committee with contributions from both sides. Then bring it to the floor for amendment and debate and see if we can pass something that will be imperfect, full of compromises, and not very pleasing to implacable partisans on either side but that might provide workable solutions to problems Americans are struggling with today.”

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Light Therapy May Treat Excessive Daytime Sleepiness in Parkinson’s Disease

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Two weeks of timed bright light therapy significantly reduced patients’ sleepiness, compared with placebo.

Light therapy may reduce excessive daytime sleepiness and improve sleep quality in patients with Parkinson’s disease, according to trial results published in the April issue of JAMA Neurology. The treatment modality is well tolerated, widely available, and “relatively easy to prescribe and incorporate into a clinical practice,” said Aleksandar Videnovic, MD, a neurologist at Massachusetts General Hospital in Boston, and colleagues.

Aleksandar Videnovic, MD

Impaired sleep and alertness are common nonmotor manifestations of Parkinson’s disease with limited treatment options. Patients’ sleep disturbances have been attributed to Parkinson’s disease symptoms, adverse medication effects, and neurodegeneration of central sleep regulatory areas. Altered circadian rhythms also may play a role. Supplemental exposure to bright light improves sleep quality and daytime vigilance in healthy older people and patients with dementia, but the treatment modality has not been studied systematically in patients with Parkinson’s disease, the researchers said.

One-Hour Treatment Intervals

To determine the safety and efficacy of light therapy on excessive daytime sleepiness associated with Parkinson’s disease, Dr. Videnovic and colleagues conducted a randomized, placebo-controlled trial.

They enrolled 31 patients with Parkinson’s disease and excessive daytime sleepiness (ie, an Epworth Sleepiness Scale score of 12 or greater). Patients were receiving stable dopaminergic therapy and did not have cognitive impairment or a primary sleep disorder. Investigators randomized participants 1:1 to receive bright light therapy (10,000 lux) or a control condition of dim-red light therapy (less than 300 lux). After a two-week baseline phase, participants received light therapy in one-hour intervals twice daily—in the morning (between 9 am and 11 am) and in the afternoon (between 5 pm and 7 pm)—for 14 days. The primary outcome measure was change in Epworth Sleepiness Scale score from baseline. During the study, each patient wore an actigraphy monitor and completed a daily sleep log and various other assessments.

During treatment, a light box was placed 86.4 cm away from the patient. Participants were instructed to sit quietly and not nap. They could listen to music or audiobooks.

The 31 patients (18 females) had an average age of about 63 (range, 32 to 77) and an average disease duration of about six years. Among patients who received bright light therapy, mean Epworth Sleepiness Scale score significantly improved from 15.81 at baseline to 11.19 post intervention. The improvement was significantly greater than that for patients in the control group, who had a mean Epworth Sleepiness Scale score of 15.47 at baseline and 13.67 post intervention.

Improvements in sleep quality, latency, and fragmentation were significantly greater in the bright light therapy group than in the control group. In both treatment arms, light therapy was associated with increased daily physical activity, as assessed by actigraphy, and reduced disease severity, as assessed by the Unified Parkinson’s Disease Rating Scale. Light therapy was not associated with significant changes in depression, anxiety, or quality of life.

In the active treatment group, one patient reported headache, and another patient reported sleepiness. One participant in the control group reported itchy eyes. The adverse events resolved spontaneously, and adherence to the study protocol was excellent, the researchers said.

Although improvement in the control arm may have been due to the placebo effect, it is also possible that “anchoring the light therapy to a strict twice-daily regimen provided means for structuring daily activities, which itself may be an interesting possible mechanism underlying the beneficial effects of … light therapy,” Dr. Videnovic and colleagues said. Future studies should address the optimal treatment parameters for light therapy in Parkinson’s disease, they added.

Whether light therapy produces direct alerting effects, influences the circadian system, or works through another mechanism is not clear. A limitation of the study was that light levels were not measured throughout the day, so patients in the control group could have received more light from other sources overall, compared with patients in the active treatment group, the investigators noted.

Chronobiologic Interventions

The study shows that chronobiologic interventions “can be used therapeutically in patients with Parkinson’s disease” and “introduce a new concept into the much-studied phenomenon of disturbed sleep and wakefulness in Parkinson’s disease,” said Birgit Högl, MD, of the Department of Neurology at the Medical University of Innsbruck in Austria, in an accompanying editorial. Although the study of chronobiology is complex, certain aspects of chronobiology can be “integrated into routine medical practice and improve outcomes for patients,” Dr. Högl said.

Jake Remaly

Suggested Reading

Högl B. Circadian rhythms and chronotherapeutics-Underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74(4):387-388.

Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: A randomized clinical trial. JAMA Neurol. 2017;74(4):411-418.

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Two weeks of timed bright light therapy significantly reduced patients’ sleepiness, compared with placebo.
Two weeks of timed bright light therapy significantly reduced patients’ sleepiness, compared with placebo.

Light therapy may reduce excessive daytime sleepiness and improve sleep quality in patients with Parkinson’s disease, according to trial results published in the April issue of JAMA Neurology. The treatment modality is well tolerated, widely available, and “relatively easy to prescribe and incorporate into a clinical practice,” said Aleksandar Videnovic, MD, a neurologist at Massachusetts General Hospital in Boston, and colleagues.

Aleksandar Videnovic, MD

Impaired sleep and alertness are common nonmotor manifestations of Parkinson’s disease with limited treatment options. Patients’ sleep disturbances have been attributed to Parkinson’s disease symptoms, adverse medication effects, and neurodegeneration of central sleep regulatory areas. Altered circadian rhythms also may play a role. Supplemental exposure to bright light improves sleep quality and daytime vigilance in healthy older people and patients with dementia, but the treatment modality has not been studied systematically in patients with Parkinson’s disease, the researchers said.

One-Hour Treatment Intervals

To determine the safety and efficacy of light therapy on excessive daytime sleepiness associated with Parkinson’s disease, Dr. Videnovic and colleagues conducted a randomized, placebo-controlled trial.

They enrolled 31 patients with Parkinson’s disease and excessive daytime sleepiness (ie, an Epworth Sleepiness Scale score of 12 or greater). Patients were receiving stable dopaminergic therapy and did not have cognitive impairment or a primary sleep disorder. Investigators randomized participants 1:1 to receive bright light therapy (10,000 lux) or a control condition of dim-red light therapy (less than 300 lux). After a two-week baseline phase, participants received light therapy in one-hour intervals twice daily—in the morning (between 9 am and 11 am) and in the afternoon (between 5 pm and 7 pm)—for 14 days. The primary outcome measure was change in Epworth Sleepiness Scale score from baseline. During the study, each patient wore an actigraphy monitor and completed a daily sleep log and various other assessments.

During treatment, a light box was placed 86.4 cm away from the patient. Participants were instructed to sit quietly and not nap. They could listen to music or audiobooks.

The 31 patients (18 females) had an average age of about 63 (range, 32 to 77) and an average disease duration of about six years. Among patients who received bright light therapy, mean Epworth Sleepiness Scale score significantly improved from 15.81 at baseline to 11.19 post intervention. The improvement was significantly greater than that for patients in the control group, who had a mean Epworth Sleepiness Scale score of 15.47 at baseline and 13.67 post intervention.

Improvements in sleep quality, latency, and fragmentation were significantly greater in the bright light therapy group than in the control group. In both treatment arms, light therapy was associated with increased daily physical activity, as assessed by actigraphy, and reduced disease severity, as assessed by the Unified Parkinson’s Disease Rating Scale. Light therapy was not associated with significant changes in depression, anxiety, or quality of life.

In the active treatment group, one patient reported headache, and another patient reported sleepiness. One participant in the control group reported itchy eyes. The adverse events resolved spontaneously, and adherence to the study protocol was excellent, the researchers said.

Although improvement in the control arm may have been due to the placebo effect, it is also possible that “anchoring the light therapy to a strict twice-daily regimen provided means for structuring daily activities, which itself may be an interesting possible mechanism underlying the beneficial effects of … light therapy,” Dr. Videnovic and colleagues said. Future studies should address the optimal treatment parameters for light therapy in Parkinson’s disease, they added.

Whether light therapy produces direct alerting effects, influences the circadian system, or works through another mechanism is not clear. A limitation of the study was that light levels were not measured throughout the day, so patients in the control group could have received more light from other sources overall, compared with patients in the active treatment group, the investigators noted.

Chronobiologic Interventions

The study shows that chronobiologic interventions “can be used therapeutically in patients with Parkinson’s disease” and “introduce a new concept into the much-studied phenomenon of disturbed sleep and wakefulness in Parkinson’s disease,” said Birgit Högl, MD, of the Department of Neurology at the Medical University of Innsbruck in Austria, in an accompanying editorial. Although the study of chronobiology is complex, certain aspects of chronobiology can be “integrated into routine medical practice and improve outcomes for patients,” Dr. Högl said.

Jake Remaly

Suggested Reading

Högl B. Circadian rhythms and chronotherapeutics-Underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74(4):387-388.

Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: A randomized clinical trial. JAMA Neurol. 2017;74(4):411-418.

Light therapy may reduce excessive daytime sleepiness and improve sleep quality in patients with Parkinson’s disease, according to trial results published in the April issue of JAMA Neurology. The treatment modality is well tolerated, widely available, and “relatively easy to prescribe and incorporate into a clinical practice,” said Aleksandar Videnovic, MD, a neurologist at Massachusetts General Hospital in Boston, and colleagues.

Aleksandar Videnovic, MD

Impaired sleep and alertness are common nonmotor manifestations of Parkinson’s disease with limited treatment options. Patients’ sleep disturbances have been attributed to Parkinson’s disease symptoms, adverse medication effects, and neurodegeneration of central sleep regulatory areas. Altered circadian rhythms also may play a role. Supplemental exposure to bright light improves sleep quality and daytime vigilance in healthy older people and patients with dementia, but the treatment modality has not been studied systematically in patients with Parkinson’s disease, the researchers said.

One-Hour Treatment Intervals

To determine the safety and efficacy of light therapy on excessive daytime sleepiness associated with Parkinson’s disease, Dr. Videnovic and colleagues conducted a randomized, placebo-controlled trial.

They enrolled 31 patients with Parkinson’s disease and excessive daytime sleepiness (ie, an Epworth Sleepiness Scale score of 12 or greater). Patients were receiving stable dopaminergic therapy and did not have cognitive impairment or a primary sleep disorder. Investigators randomized participants 1:1 to receive bright light therapy (10,000 lux) or a control condition of dim-red light therapy (less than 300 lux). After a two-week baseline phase, participants received light therapy in one-hour intervals twice daily—in the morning (between 9 am and 11 am) and in the afternoon (between 5 pm and 7 pm)—for 14 days. The primary outcome measure was change in Epworth Sleepiness Scale score from baseline. During the study, each patient wore an actigraphy monitor and completed a daily sleep log and various other assessments.

During treatment, a light box was placed 86.4 cm away from the patient. Participants were instructed to sit quietly and not nap. They could listen to music or audiobooks.

The 31 patients (18 females) had an average age of about 63 (range, 32 to 77) and an average disease duration of about six years. Among patients who received bright light therapy, mean Epworth Sleepiness Scale score significantly improved from 15.81 at baseline to 11.19 post intervention. The improvement was significantly greater than that for patients in the control group, who had a mean Epworth Sleepiness Scale score of 15.47 at baseline and 13.67 post intervention.

Improvements in sleep quality, latency, and fragmentation were significantly greater in the bright light therapy group than in the control group. In both treatment arms, light therapy was associated with increased daily physical activity, as assessed by actigraphy, and reduced disease severity, as assessed by the Unified Parkinson’s Disease Rating Scale. Light therapy was not associated with significant changes in depression, anxiety, or quality of life.

In the active treatment group, one patient reported headache, and another patient reported sleepiness. One participant in the control group reported itchy eyes. The adverse events resolved spontaneously, and adherence to the study protocol was excellent, the researchers said.

Although improvement in the control arm may have been due to the placebo effect, it is also possible that “anchoring the light therapy to a strict twice-daily regimen provided means for structuring daily activities, which itself may be an interesting possible mechanism underlying the beneficial effects of … light therapy,” Dr. Videnovic and colleagues said. Future studies should address the optimal treatment parameters for light therapy in Parkinson’s disease, they added.

Whether light therapy produces direct alerting effects, influences the circadian system, or works through another mechanism is not clear. A limitation of the study was that light levels were not measured throughout the day, so patients in the control group could have received more light from other sources overall, compared with patients in the active treatment group, the investigators noted.

Chronobiologic Interventions

The study shows that chronobiologic interventions “can be used therapeutically in patients with Parkinson’s disease” and “introduce a new concept into the much-studied phenomenon of disturbed sleep and wakefulness in Parkinson’s disease,” said Birgit Högl, MD, of the Department of Neurology at the Medical University of Innsbruck in Austria, in an accompanying editorial. Although the study of chronobiology is complex, certain aspects of chronobiology can be “integrated into routine medical practice and improve outcomes for patients,” Dr. Högl said.

Jake Remaly

Suggested Reading

Högl B. Circadian rhythms and chronotherapeutics-Underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74(4):387-388.

Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: A randomized clinical trial. JAMA Neurol. 2017;74(4):411-418.

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More treatments becoming available for tardive dyskinesia

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– The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.

“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.

Dr. Ira D. Glick


The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.

Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.

A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).

Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.

“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.

Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.

Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.

Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.

“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.

However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.

The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
 

 

Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.

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– The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.

“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.

Dr. Ira D. Glick


The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.

Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.

A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).

Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.

“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.

Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.

Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.

Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.

“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.

However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.

The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
 

 

Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.

 

– The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.

“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.

Dr. Ira D. Glick


The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.

Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.

A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).

Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.

“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.

Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.

Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.

Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.

“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.

However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.

The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
 

 

Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.

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