MD

BY AYAN KUSARI AND CATALINA MATIZ, MD

The patient was diagnosed with eruptive vellus hair cysts (EVHC). Treatment with a keratolytic, such as 12% lactic acid cream, was recommended. Hydrocortisone 2.5% once daily as needed also was recommended to treat the patient’s itch.

EVHC are benign middermal cysts characterized by epidermoid keratinization of the cyst wall, as well as lamellar keratin and vellus hairs within the cyst.¹ The term “eruptive vellus hair cysts” was first used to describe a longstanding hyperpigmented, monomorphous papular eruption in two children by Esterly, Fretzin, and Pinkus in 1977.² Clinically, EVHC present as 1- to 3-mm follicular, dome-shaped papules that are often skin-colored but also have been described as being brown, gray, green or black colored.^3,4 They appear suddenly and sometimes are associated with mild tenderness and pruritus.^1,5 EVHC most commonly present on the anterior chest but also can present on the upper and lower extremities, face, neck, axillae, and buttocks.⁴

Furthermore, although spontaneous resolution is possible through transepidermal elimination of cyst products, cases may persist for years in the absence of treatment.¹

Accurate diagnosis of eruptive vellus hair cysts is important to guide therapy.

Keratosis pilaris consists of follicular-based papules with variable erythema.⁴ It may be widespread – including over the anterior chest – but is most commonly seen on the cheeks, extensor surfaces of proximal upper extremities, and the anterior thighs.⁴ It is related to excessive keratinization, which leads to formation of horny plugs within hair-follicle orifices.¹

Steatocystoma multiplex is typically characterized by firm, yellow-to-flesh–colored dermal cysts ranging from a few millimeters to 1 cm in size.¹ They are sometimes clinically hard to distinguish from EVHC, and both are associated with keratin 17 gene mutations and type 2 pachyonychia congenita.¹ Nonetheless, this patient’s lesions did not have any features – such as size or drainage – that would point toward steatocystoma multiplex or other skin findings suggestive of pachyonychia congenita.

Superficial folliculitis, also known as Bockhart’s impetigo, is an infection of the follicular ostium and typically presents with perifollicular pustules on an erythematous base that may be painful or pruritic and can occur throughout the corpus, including the anterior trunk.¹

Acne vulgaris is a very common disease that involves the pilosebaceous unit and occurs most frequently on the face, back, upper arms, and chest. However, it is characterized by open and closed comedones, papules, and pustules and, in severe cases, nodules and cysts that may leave postinflammatory hyperpigmentation and scarring. Tiny, hyperpigmented, dome-shaped macules occurring exclusively on the chest would not be characteristic.

Patients with hypohidrotic ectodermal dysplasia, also known as Christ-Siemens-Touraine syndrome, can present with EVHC. This condition is characterized by a triad of fair, sparse short hair; hyperthermia related to decreased sweating; and missing teeth.⁴ Although EVHC have been reported in association with hypohidrotic ectodermal dysplasia, this patient does not have any of the dysmorphic features associated with this syndrome.¹¹

Patients with pachyonychia congenita (type 2) also may have EVHC as part of their presentation, but this patient does not have nail dystrophy, focal palmoplantar keratoderma, follicular keratoses, or multiple steatocysts which also are features of this condition.⁴

Treatment may be offered to patients who are distressed by the lesions or seek cosmesis. A 2012 review of 220 cases of EVHC found that topical retinoic acid, incision/excision, CO2 laser, erbium:yttrium-aluminum-garnet laser, needle evacuation, dermabrasion, and 10% urea cream were each associated with successful treatment in multiple cases.³

Forty years have passed since EVHC was identified as a distinct disease entity. Despite this, eruptive vellus hair cysts remains somewhat understudied, and further research is needed to determine an ideal treatment algorithm for patients with this condition. Our approach was to attempt noninvasive keratolytic therapy before considering retinoids or surgical options; we also recommended steroid treatment for symptom relief. Providers should keep EVHC in the differential for eruptions consisting of tiny papules so that appropriate treatment may be offered.

Dr. Matiz is a pediatric dermatologist at Rady Children’s Hospital, San Diego, and an assistant clinical professor in the department of pediatric and adolescent dermatology at the University of California, San Diego. Mr. Kusari is a medical student at the University of California, San Diego. Dr. Matiz and Mr. Kusari said they had no relevant financial disclosures.

Email them at pdnews@frontlinemedcom.com.

References

1. “Dermatology.” 3rd ed. (Philadelphia: Saunders, 2012).

2. Arch Dermatol. 1977 Apr;113(4):500-3.

3. Am J Clin Dermatol. 2012 Feb 1;13(1):19-28.

4. “Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence.” 4th ed. (Philadelphia: Saunders, 2011).

5. Indian Dermatol Online J. 2013 Jul;4(3):213-5.

6. J Am Acad Dermatol. 1980 Oct;3(4):425-9.

7. Am J Dermatopathol. 1997 Jun;19(3):250-3.

8. Hum Mol Genet. 1998 Jul;7(7):1143-8.

9. Dermatology. 1998;196(4):392-6.

10. Arch Dermatol. 1986 Feb;122(2):141.

11. Int J Dermatol. 2001 Jun;40(6):401-2.

BY AYAN KUSARI AND CATALINA MATIZ, MD

The patient was diagnosed with eruptive vellus hair cysts (EVHC). Treatment with a keratolytic, such as 12% lactic acid cream, was recommended. Hydrocortisone 2.5% once daily as needed also was recommended to treat the patient’s itch.

EVHC are benign middermal cysts characterized by epidermoid keratinization of the cyst wall, as well as lamellar keratin and vellus hairs within the cyst.¹ The term “eruptive vellus hair cysts” was first used to describe a longstanding hyperpigmented, monomorphous papular eruption in two children by Esterly, Fretzin, and Pinkus in 1977.² Clinically, EVHC present as 1- to 3-mm follicular, dome-shaped papules that are often skin-colored but also have been described as being brown, gray, green or black colored.^3,4 They appear suddenly and sometimes are associated with mild tenderness and pruritus.^1,5 EVHC most commonly present on the anterior chest but also can present on the upper and lower extremities, face, neck, axillae, and buttocks.⁴

Furthermore, although spontaneous resolution is possible through transepidermal elimination of cyst products, cases may persist for years in the absence of treatment.¹

Accurate diagnosis of eruptive vellus hair cysts is important to guide therapy.

Keratosis pilaris consists of follicular-based papules with variable erythema.⁴ It may be widespread – including over the anterior chest – but is most commonly seen on the cheeks, extensor surfaces of proximal upper extremities, and the anterior thighs.⁴ It is related to excessive keratinization, which leads to formation of horny plugs within hair-follicle orifices.¹

Steatocystoma multiplex is typically characterized by firm, yellow-to-flesh–colored dermal cysts ranging from a few millimeters to 1 cm in size.¹ They are sometimes clinically hard to distinguish from EVHC, and both are associated with keratin 17 gene mutations and type 2 pachyonychia congenita.¹ Nonetheless, this patient’s lesions did not have any features – such as size or drainage – that would point toward steatocystoma multiplex or other skin findings suggestive of pachyonychia congenita.

Superficial folliculitis, also known as Bockhart’s impetigo, is an infection of the follicular ostium and typically presents with perifollicular pustules on an erythematous base that may be painful or pruritic and can occur throughout the corpus, including the anterior trunk.¹

Acne vulgaris is a very common disease that involves the pilosebaceous unit and occurs most frequently on the face, back, upper arms, and chest. However, it is characterized by open and closed comedones, papules, and pustules and, in severe cases, nodules and cysts that may leave postinflammatory hyperpigmentation and scarring. Tiny, hyperpigmented, dome-shaped macules occurring exclusively on the chest would not be characteristic.

Patients with hypohidrotic ectodermal dysplasia, also known as Christ-Siemens-Touraine syndrome, can present with EVHC. This condition is characterized by a triad of fair, sparse short hair; hyperthermia related to decreased sweating; and missing teeth.⁴ Although EVHC have been reported in association with hypohidrotic ectodermal dysplasia, this patient does not have any of the dysmorphic features associated with this syndrome.¹¹

Patients with pachyonychia congenita (type 2) also may have EVHC as part of their presentation, but this patient does not have nail dystrophy, focal palmoplantar keratoderma, follicular keratoses, or multiple steatocysts which also are features of this condition.⁴

Treatment may be offered to patients who are distressed by the lesions or seek cosmesis. A 2012 review of 220 cases of EVHC found that topical retinoic acid, incision/excision, CO2 laser, erbium:yttrium-aluminum-garnet laser, needle evacuation, dermabrasion, and 10% urea cream were each associated with successful treatment in multiple cases.³

Forty years have passed since EVHC was identified as a distinct disease entity. Despite this, eruptive vellus hair cysts remains somewhat understudied, and further research is needed to determine an ideal treatment algorithm for patients with this condition. Our approach was to attempt noninvasive keratolytic therapy before considering retinoids or surgical options; we also recommended steroid treatment for symptom relief. Providers should keep EVHC in the differential for eruptions consisting of tiny papules so that appropriate treatment may be offered.

Dr. Matiz is a pediatric dermatologist at Rady Children’s Hospital, San Diego, and an assistant clinical professor in the department of pediatric and adolescent dermatology at the University of California, San Diego. Mr. Kusari is a medical student at the University of California, San Diego. Dr. Matiz and Mr. Kusari said they had no relevant financial disclosures.

Email them at pdnews@frontlinemedcom.com.

References

1. “Dermatology.” 3rd ed. (Philadelphia: Saunders, 2012).

2. Arch Dermatol. 1977 Apr;113(4):500-3.

3. Am J Clin Dermatol. 2012 Feb 1;13(1):19-28.

4. “Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence.” 4th ed. (Philadelphia: Saunders, 2011).

5. Indian Dermatol Online J. 2013 Jul;4(3):213-5.

6. J Am Acad Dermatol. 1980 Oct;3(4):425-9.

7. Am J Dermatopathol. 1997 Jun;19(3):250-3.

8. Hum Mol Genet. 1998 Jul;7(7):1143-8.

9. Dermatology. 1998;196(4):392-6.

10. Arch Dermatol. 1986 Feb;122(2):141.

11. Int J Dermatol. 2001 Jun;40(6):401-2.

BY AYAN KUSARI AND CATALINA MATIZ, MD

The patient was diagnosed with eruptive vellus hair cysts (EVHC). Treatment with a keratolytic, such as 12% lactic acid cream, was recommended. Hydrocortisone 2.5% once daily as needed also was recommended to treat the patient’s itch.

EVHC are benign middermal cysts characterized by epidermoid keratinization of the cyst wall, as well as lamellar keratin and vellus hairs within the cyst.¹ The term “eruptive vellus hair cysts” was first used to describe a longstanding hyperpigmented, monomorphous papular eruption in two children by Esterly, Fretzin, and Pinkus in 1977.² Clinically, EVHC present as 1- to 3-mm follicular, dome-shaped papules that are often skin-colored but also have been described as being brown, gray, green or black colored.^3,4 They appear suddenly and sometimes are associated with mild tenderness and pruritus.^1,5 EVHC most commonly present on the anterior chest but also can present on the upper and lower extremities, face, neck, axillae, and buttocks.⁴

Furthermore, although spontaneous resolution is possible through transepidermal elimination of cyst products, cases may persist for years in the absence of treatment.¹

Accurate diagnosis of eruptive vellus hair cysts is important to guide therapy.

Keratosis pilaris consists of follicular-based papules with variable erythema.⁴ It may be widespread – including over the anterior chest – but is most commonly seen on the cheeks, extensor surfaces of proximal upper extremities, and the anterior thighs.⁴ It is related to excessive keratinization, which leads to formation of horny plugs within hair-follicle orifices.¹

Steatocystoma multiplex is typically characterized by firm, yellow-to-flesh–colored dermal cysts ranging from a few millimeters to 1 cm in size.¹ They are sometimes clinically hard to distinguish from EVHC, and both are associated with keratin 17 gene mutations and type 2 pachyonychia congenita.¹ Nonetheless, this patient’s lesions did not have any features – such as size or drainage – that would point toward steatocystoma multiplex or other skin findings suggestive of pachyonychia congenita.

Superficial folliculitis, also known as Bockhart’s impetigo, is an infection of the follicular ostium and typically presents with perifollicular pustules on an erythematous base that may be painful or pruritic and can occur throughout the corpus, including the anterior trunk.¹

Acne vulgaris is a very common disease that involves the pilosebaceous unit and occurs most frequently on the face, back, upper arms, and chest. However, it is characterized by open and closed comedones, papules, and pustules and, in severe cases, nodules and cysts that may leave postinflammatory hyperpigmentation and scarring. Tiny, hyperpigmented, dome-shaped macules occurring exclusively on the chest would not be characteristic.

Patients with hypohidrotic ectodermal dysplasia, also known as Christ-Siemens-Touraine syndrome, can present with EVHC. This condition is characterized by a triad of fair, sparse short hair; hyperthermia related to decreased sweating; and missing teeth.⁴ Although EVHC have been reported in association with hypohidrotic ectodermal dysplasia, this patient does not have any of the dysmorphic features associated with this syndrome.¹¹

Patients with pachyonychia congenita (type 2) also may have EVHC as part of their presentation, but this patient does not have nail dystrophy, focal palmoplantar keratoderma, follicular keratoses, or multiple steatocysts which also are features of this condition.⁴

Treatment may be offered to patients who are distressed by the lesions or seek cosmesis. A 2012 review of 220 cases of EVHC found that topical retinoic acid, incision/excision, CO2 laser, erbium:yttrium-aluminum-garnet laser, needle evacuation, dermabrasion, and 10% urea cream were each associated with successful treatment in multiple cases.³

Forty years have passed since EVHC was identified as a distinct disease entity. Despite this, eruptive vellus hair cysts remains somewhat understudied, and further research is needed to determine an ideal treatment algorithm for patients with this condition. Our approach was to attempt noninvasive keratolytic therapy before considering retinoids or surgical options; we also recommended steroid treatment for symptom relief. Providers should keep EVHC in the differential for eruptions consisting of tiny papules so that appropriate treatment may be offered.

Dr. Matiz is a pediatric dermatologist at Rady Children’s Hospital, San Diego, and an assistant clinical professor in the department of pediatric and adolescent dermatology at the University of California, San Diego. Mr. Kusari is a medical student at the University of California, San Diego. Dr. Matiz and Mr. Kusari said they had no relevant financial disclosures.

Email them at pdnews@frontlinemedcom.com.

References

1. “Dermatology.” 3rd ed. (Philadelphia: Saunders, 2012).

2. Arch Dermatol. 1977 Apr;113(4):500-3.

3. Am J Clin Dermatol. 2012 Feb 1;13(1):19-28.

4. “Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence.” 4th ed. (Philadelphia: Saunders, 2011).

5. Indian Dermatol Online J. 2013 Jul;4(3):213-5.

6. J Am Acad Dermatol. 1980 Oct;3(4):425-9.

7. Am J Dermatopathol. 1997 Jun;19(3):250-3.

8. Hum Mol Genet. 1998 Jul;7(7):1143-8.

9. Dermatology. 1998;196(4):392-6.

10. Arch Dermatol. 1986 Feb;122(2):141.

11. Int J Dermatol. 2001 Jun;40(6):401-2.

The U.S. Army hospital at Fort Campbell, Kentucky, was named for army nurse, Colonel Florence A. Blanchfield—making it the only current army hospital named for a nurse.

Florence Aby Blanchfield was born into a large family in Shepherdstown, West Virginia, in 1882. Her mother was a nurse, and her father was a mason and stonecutter. She grew up in Oranda, Virginia, and attended both public and private schools. Following in her mother’s footsteps to become a nurse, she attended Southside Hospital Training School in Pittsburgh, Pennsylvania, and graduated in 1906. She moved to Baltimore after graduation and worked with Howard Atwood Kelly, one of the “Big Four” along with William Osler, William Henry Welch, and William Stewart Halsted who were known as the founding physicians of the Johns Hopkins Hospital.

After what must have been a remarkable experience with the innovative Kelly (inventor of many groundbreaking medical instruments and procedures, including the Kelly clamp), Blanchfield returned to Pittsburgh. She held positions of increasing responsibility over several years, including operating room supervisor at Southside Hospital and Montefiore Hospital and superintendent of the training school at Suburban General Hospital. Looking for adventure as well as service, she gave up her positions of leadership and headed to Panama in 1913 to become an operating room nurse and an anesthetist at Ancon Hospital in the U.S. Canal Zone.

As America prepared for its probable entry into World War I, Blanchfield joined the Army Nurse Corps (ANC) at age 35 to serve with the Medical School Unit of the University of Pittsburgh’s Base Hospital 27. She arrived in France in October 1917 and became acting chief nurse of Base Hospital 27 in Angers, Maine et Loire department. She also served as acting chief nurse of Camp Hospital 15 at Coëtquidan, Ille et Vil department.

Blanchfield returned to civilian life following World War I for a short period but returned to active duty in 1920. Over the next 15 years, she had several assignments within the continental U.S. and overseas in the Philippines and in Tianjin, China (formally known in English as Tientsin). In 1935, Blanchfield joined the Office of the Army Surgeon General in Washington, DC, where she was assigned to work on personnel matters in the office of the superintendent of the ANC. She became assistant superintendent in 1939, acting superintendent in 1942, and served as superintendent from June 1943 until September 1947. During World War II, she presided over the growth of the ANC from about 7,000 nurses on the day Pearl Harbor was attacked to more than 50,000 by the end of the war. She was awarded the Distinguished Service Medal for her contributions and accomplishments during World War II.

Blanchfield, a long-time senior leader in the ANC, was instrumental in many of the significant changes that took place during and after World War II, including nurses gaining full rank and benefits. This was an incremental process that culminated with passage of the Army and Navy Nurse Corps Act of April 1947, with nurses being granted full commissioned status. As a result of this act, she became a lieutenant colonel and the first woman to receive a commission in the regular army.

Blanchfield remained active in national nursing affairs after her retirement from the U.S. Army. At a time when many believed that nurses did not need specialty training, she promoted the establishment of specialized courses of study. In 1951, she received the Florence Nightingale Medal of the International Red Cross.

Blanchfield died on May 12, 1971, and was buried in the nurse’s section of Arlington National Cemetery with full military honors. In 1978, ANC leadership began a drive to memorialize Blanchfield by naming the new hospital at Fort Campbell, Kentucky, in her honor. A successful letter writing campaign by army nurses inundated the senior commander at Fort Campbell. The Colonel Florence A. Blanchfield Army Community Hospital, which was dedicated in her memory on September 17, 1982.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual your facility was named for or to offer a topic suggestion, contact us at fedprac@frontlinemedcom.com or on Facebook.

The U.S. Army hospital at Fort Campbell, Kentucky, was named for army nurse, Colonel Florence A. Blanchfield—making it the only current army hospital named for a nurse.

Florence Aby Blanchfield was born into a large family in Shepherdstown, West Virginia, in 1882. Her mother was a nurse, and her father was a mason and stonecutter. She grew up in Oranda, Virginia, and attended both public and private schools. Following in her mother’s footsteps to become a nurse, she attended Southside Hospital Training School in Pittsburgh, Pennsylvania, and graduated in 1906. She moved to Baltimore after graduation and worked with Howard Atwood Kelly, one of the “Big Four” along with William Osler, William Henry Welch, and William Stewart Halsted who were known as the founding physicians of the Johns Hopkins Hospital.

After what must have been a remarkable experience with the innovative Kelly (inventor of many groundbreaking medical instruments and procedures, including the Kelly clamp), Blanchfield returned to Pittsburgh. She held positions of increasing responsibility over several years, including operating room supervisor at Southside Hospital and Montefiore Hospital and superintendent of the training school at Suburban General Hospital. Looking for adventure as well as service, she gave up her positions of leadership and headed to Panama in 1913 to become an operating room nurse and an anesthetist at Ancon Hospital in the U.S. Canal Zone.

As America prepared for its probable entry into World War I, Blanchfield joined the Army Nurse Corps (ANC) at age 35 to serve with the Medical School Unit of the University of Pittsburgh’s Base Hospital 27. She arrived in France in October 1917 and became acting chief nurse of Base Hospital 27 in Angers, Maine et Loire department. She also served as acting chief nurse of Camp Hospital 15 at Coëtquidan, Ille et Vil department.

Blanchfield returned to civilian life following World War I for a short period but returned to active duty in 1920. Over the next 15 years, she had several assignments within the continental U.S. and overseas in the Philippines and in Tianjin, China (formally known in English as Tientsin). In 1935, Blanchfield joined the Office of the Army Surgeon General in Washington, DC, where she was assigned to work on personnel matters in the office of the superintendent of the ANC. She became assistant superintendent in 1939, acting superintendent in 1942, and served as superintendent from June 1943 until September 1947. During World War II, she presided over the growth of the ANC from about 7,000 nurses on the day Pearl Harbor was attacked to more than 50,000 by the end of the war. She was awarded the Distinguished Service Medal for her contributions and accomplishments during World War II.

Blanchfield, a long-time senior leader in the ANC, was instrumental in many of the significant changes that took place during and after World War II, including nurses gaining full rank and benefits. This was an incremental process that culminated with passage of the Army and Navy Nurse Corps Act of April 1947, with nurses being granted full commissioned status. As a result of this act, she became a lieutenant colonel and the first woman to receive a commission in the regular army.

Blanchfield remained active in national nursing affairs after her retirement from the U.S. Army. At a time when many believed that nurses did not need specialty training, she promoted the establishment of specialized courses of study. In 1951, she received the Florence Nightingale Medal of the International Red Cross.

Blanchfield died on May 12, 1971, and was buried in the nurse’s section of Arlington National Cemetery with full military honors. In 1978, ANC leadership began a drive to memorialize Blanchfield by naming the new hospital at Fort Campbell, Kentucky, in her honor. A successful letter writing campaign by army nurses inundated the senior commander at Fort Campbell. The Colonel Florence A. Blanchfield Army Community Hospital, which was dedicated in her memory on September 17, 1982.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual your facility was named for or to offer a topic suggestion, contact us at fedprac@frontlinemedcom.com or on Facebook.

The U.S. Army hospital at Fort Campbell, Kentucky, was named for army nurse, Colonel Florence A. Blanchfield—making it the only current army hospital named for a nurse.

Florence Aby Blanchfield was born into a large family in Shepherdstown, West Virginia, in 1882. Her mother was a nurse, and her father was a mason and stonecutter. She grew up in Oranda, Virginia, and attended both public and private schools. Following in her mother’s footsteps to become a nurse, she attended Southside Hospital Training School in Pittsburgh, Pennsylvania, and graduated in 1906. She moved to Baltimore after graduation and worked with Howard Atwood Kelly, one of the “Big Four” along with William Osler, William Henry Welch, and William Stewart Halsted who were known as the founding physicians of the Johns Hopkins Hospital.

After what must have been a remarkable experience with the innovative Kelly (inventor of many groundbreaking medical instruments and procedures, including the Kelly clamp), Blanchfield returned to Pittsburgh. She held positions of increasing responsibility over several years, including operating room supervisor at Southside Hospital and Montefiore Hospital and superintendent of the training school at Suburban General Hospital. Looking for adventure as well as service, she gave up her positions of leadership and headed to Panama in 1913 to become an operating room nurse and an anesthetist at Ancon Hospital in the U.S. Canal Zone.

As America prepared for its probable entry into World War I, Blanchfield joined the Army Nurse Corps (ANC) at age 35 to serve with the Medical School Unit of the University of Pittsburgh’s Base Hospital 27. She arrived in France in October 1917 and became acting chief nurse of Base Hospital 27 in Angers, Maine et Loire department. She also served as acting chief nurse of Camp Hospital 15 at Coëtquidan, Ille et Vil department.

Blanchfield returned to civilian life following World War I for a short period but returned to active duty in 1920. Over the next 15 years, she had several assignments within the continental U.S. and overseas in the Philippines and in Tianjin, China (formally known in English as Tientsin). In 1935, Blanchfield joined the Office of the Army Surgeon General in Washington, DC, where she was assigned to work on personnel matters in the office of the superintendent of the ANC. She became assistant superintendent in 1939, acting superintendent in 1942, and served as superintendent from June 1943 until September 1947. During World War II, she presided over the growth of the ANC from about 7,000 nurses on the day Pearl Harbor was attacked to more than 50,000 by the end of the war. She was awarded the Distinguished Service Medal for her contributions and accomplishments during World War II.

Blanchfield, a long-time senior leader in the ANC, was instrumental in many of the significant changes that took place during and after World War II, including nurses gaining full rank and benefits. This was an incremental process that culminated with passage of the Army and Navy Nurse Corps Act of April 1947, with nurses being granted full commissioned status. As a result of this act, she became a lieutenant colonel and the first woman to receive a commission in the regular army.

Blanchfield remained active in national nursing affairs after her retirement from the U.S. Army. At a time when many believed that nurses did not need specialty training, she promoted the establishment of specialized courses of study. In 1951, she received the Florence Nightingale Medal of the International Red Cross.

Blanchfield died on May 12, 1971, and was buried in the nurse’s section of Arlington National Cemetery with full military honors. In 1978, ANC leadership began a drive to memorialize Blanchfield by naming the new hospital at Fort Campbell, Kentucky, in her honor. A successful letter writing campaign by army nurses inundated the senior commander at Fort Campbell. The Colonel Florence A. Blanchfield Army Community Hospital, which was dedicated in her memory on September 17, 1982.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual your facility was named for or to offer a topic suggestion, contact us at fedprac@frontlinemedcom.com or on Facebook.

As we head into vacation season and the dog days of summer, let’s reflect for a few minutes on some of the very important advances we heard about at this year’s annual meeting of the American Society of Clinical Oncology in Chicago. Nearly 40,000 individuals registered for the conference, an indication of both the interest and the excitement around the new agents and the emerging clinical trial data. Scientific sessions dedicated to the use of combination immunotherapy, the role of antibody drug conjugates, and targeting molecular aberrations with small molecules were among the most popular (p. e236).

As we head into vacation season and the dog days of summer, let’s reflect for a few minutes on some of the very important advances we heard about at this year’s annual meeting of the American Society of Clinical Oncology in Chicago. Nearly 40,000 individuals registered for the conference, an indication of both the interest and the excitement around the new agents and the emerging clinical trial data. Scientific sessions dedicated to the use of combination immunotherapy, the role of antibody drug conjugates, and targeting molecular aberrations with small molecules were among the most popular (p. e236).

As we head into vacation season and the dog days of summer, let’s reflect for a few minutes on some of the very important advances we heard about at this year’s annual meeting of the American Society of Clinical Oncology in Chicago. Nearly 40,000 individuals registered for the conference, an indication of both the interest and the excitement around the new agents and the emerging clinical trial data. Scientific sessions dedicated to the use of combination immunotherapy, the role of antibody drug conjugates, and targeting molecular aberrations with small molecules were among the most popular (p. e236).

Take-Home Points

• Careful evaluation is key in attributing knee pain to patellofemoral cartilage lesions-that is, in making a "diagnosis by exclusion".
• Initial treatment is nonoperative management focused on weight loss and extensive "core-to-floor" rehabilitation.
• Optimization of anatomy and biomechanics is crucial.
• Factors important in surgical decision-making incude defect location and size, subchondral bone status, unipolar vs bipolar lesions, and previous cartilage procedure.
• The most commonly used surgical procedures-autologous chondrocyte implantation, osteochondral autograft transfer, and osteochondral allograft-have demonstrated improved intermediate-term outcomes.

Patellofemoral (PF) pain is often a component of more general anterior knee pain. One source of PF pain is chondral lesions. As these lesions are commonly seen on magnetic resonance imaging (MRI) and during arthroscopy, it is necessary to differentiate incidental and symptomatic lesions.¹ In addition, the correlation between symptoms and lesion presence and severity is poor.

PF pain is multifactorial (structural lesions, malalignment, deconditioning, muscle imbalance and overuse) and can coexist with other lesions in the knee (ligament tears, meniscal injuries, and cartilage lesions in other compartments). Therefore, careful evaluation is key in attributing knee pain to PF cartilage lesions—that is, in making a "diagnosis by exclusion."

From the start, it must be appreciated that the vast majority of patients will not require surgery, and many who require surgery for pain will not require cartilage restoration. One key to success with PF patients is a good working relationship with an experienced physical therapist.

Etiology

The primary causes of PF cartilage lesions are patellar instability, chronic maltracking without instability, direct trauma, repetitive microtrauma, and idiopathic.

Patellar Instability

Patients with patellar instability often present with underlying anatomical risk factors (eg, trochlear dysplasia, increased Q-angle/tibial tubercle-trochlear groove [TT-TG] distance, patella alta, and unbalanced medial and lateral soft tissues²). These factors should be addressed before surgery.

Patellar instability can cause cartilage damage during the dislocation event or by chronic subluxation. Cartilage becomes damaged in up to 96% of patellar dislocations.³ Most commonly, the damage consists of fissuring and/or fibrillation, but chondral and osteochondral fractures can occur as well. During dislocation, the medial patella strikes the lateral aspect of the femur, and, as the knee collapses into flexion, the lateral aspect of the proximal lateral femoral condyle (weight-bearing area) can sustain damage. In the patella, typically the injury is distal-medial (occasionally crossing the median ridge). A shear lesion may involve the chondral surface or be osteochondral (Figure 1A).

Chronic Maltracking Without Instability

Chronic maltracking is usually related to anatomical abnormalities, which include the same factors that can cause patellar instability. A common combination is trochlear dysplasia, increased TT-TG or TT-posterior cruciate ligament distance, and lateral soft-tissue contracture. These are often seen in PF joints that progress to lateral PF arthritis. As lateral PF arthritis progresses, lateral soft-tissue contracture worsens, compounding symptoms of laterally based pain. With respect to cartilage repair, these joints can be treated if recognized early; however, once osteoarthritis is fully established in the joint, facetectomy or PF replacement may be necessary.

Direct Trauma

With the knee in flexion during a direct trauma over the patella (eg, fall or dashboard trauma), all zones of cartilage and subchondral bone in both patella and trochlea can be injured, leading to macrostructural damage, chondral/osteochondral fracture, or, with a subcritical force, microstructural damage and chondrocyte death, subsequently causing cartilage degeneration (cartilage may look normal initially; the matrix takes months to years to deteriorate). Direct trauma usually occurs with the knee flexed. Therefore, these lesions typically are located in the distal trochlea and superior pole of the patella.

Repetitive Microtrauma

Minor injuries, which by themselves do not immediately cause apparent chondral or osteochondral fractures, may eventually exceed the capacity of natural cartilage homeostasis and result in repetitive microtrauma. Common causes are repeated jumping (as in basketball and volleyball) and prolonged flexed-knee position (eg, what a baseball catcher experiences), which may also be associated with other lesions caused by extensor apparatus overload (eg, quadriceps tendon or patellar tendon tendinitis, and fat pad impingement syndrome).

Idiopathic

In a subset of patients with osteochondritis dissecans, the patella is the lesion site. In another subset, idiopathic lesions may be related to a genetic predisposition to osteoarthritis and may not be restricted to the PF joint. In some cases, the PF joint is the first compartment to degenerate and is the most symptomatic in a setting of truly tricompartmental disease. In these cases, treating only the PF lesion can result in functional failure, owing to disease progression in other compartments. Even mild disease in other compartments should be carefully evaluated.

History and Physical Examination

Patients often report a history of anterior knee pain that worsens with stair use, prolonged sitting, and flexed-knee activities (eg, squatting). Compared with pain alone, swelling, though not specific to cartilage disease, is more suspicious for a cartilage etiology. Identifying the cartilage defect as the sole source of pain is particularly difficult in patients with recurrent patellar instability. In these patients, pain and swelling, even between instability episodes, suggest that cartilage damage is at least a component of the symptomology.

Important diagnostic components of physical examination are gait analysis, tibiofemoral alignment, and patellar alignment in all 3 planes, both static and functional. Patella-specific measurements include medial-lateral position and quadrants of excursion, lateral tilt, and patella alta, as well as J-sign and subluxation with quadriceps contraction in extension.

It is also important to document effusion; crepitus; active and passive range of motion (spine, hips, knees); site of pain or tenderness to palpation (medial, lateral, distal, retropatellar) and whether it matches the complaints and the location of the cartilage lesion; results of the grind test (placing downward force on the patella during flexion and extension) and whether they match the flexion angle of the tenderness and the flexion angle in which the cartilage lesion has increased PF contact; ligamentous and soft-tissue stability or imbalance (tibiofemoral and patellar; apprehension test, glide test, tilt test); and muscle strength, flexibility, and atrophy of the core (abdomen, dorsal and hip muscles) and lower extremities (quadriceps, hamstrings, gastrocnemius).

Imaging

Imaging should be used to evaluate both PF alignment and the cartilage lesions. For alignment, standard radiographs (weight-bearing knee sequence and axial view; full limb length when needed), computed tomography, and MRI can be used.

Meaningful evaluation requires MRI with cartilage-specific sequences, including standard spin-echo (SE) and gradient-recalled echo (GRE), fast SE, and, for cartilage morphology, T2-weighted fat suppression (FS) and 3-dimensional SE and GRE.⁵ For evaluation of cartilage function and metabolism, the collagen network, and proteoglycan content in the knee cartilage matrix, consideration should be given to compositional assessment techniques, such as T2 mapping, delayed gadolinium-enhanced MRI of cartilage, T1ρ imaging, sodium imaging, and diffusion-weighted sequences.⁵ Use of the latter functional sequences is still debatable, and these sequences are not widely available.

Treatment

In general, the initial approach is nonoperative management focused on weight loss and extensive core-to-floor rehabilitation, unless surgery is specifically indicated (eg, for loose body removal or osteochondral fracture reattachment). Rehabilitation focuses on achieving adequate range of motion of the spine, hips, and knees along with muscle strength and flexibility of the core (abdomen, dorsal and hip muscles) and lower limbs (quadriceps, hamstrings, gastrocnemius). Rehabilitation is not defined by time but rather by development of an optimized soft-tissue envelope that decreases joint reactive forces. The full process can take 6 to 9 months, but there should be some improvement by 3 months.

Corticosteroid, hyaluronic acid,⁶ or platelet-rich plasma⁷ injections can provide temporary relief and facilitate rehabilitation in the setting of pain inhibition. As stand-alone treatment, injections are more suitable for more diffuse degenerative lesions in older and low-demand patients than for focal traumatic lesions in young and high-demand patients.

Surgery is indicated for full-thickness or nearly full-thickness lesions (International Cartilage Repair Society grade 3a or higher) >1 cm² after failed conservative treatment.

Optimization of anatomy and biomechanics is crucial, as persistent abnormalities lead to high rates of failure of cartilage procedures, and correction of those factors results in outcomes similar to those of patients without such abnormal anatomy.⁸ The procedures most commonly used to improve patellar tracking or unloading in the PF compartment are lateral retinacular lengthening and TT transfer: medialization and/or distalization for correction of malalignment, and straight anteriorization or anteromedialization for unloading. These procedures can improve symptoms and function in lateral and distal patellar and trochlear lesions even without the addition of a cartilage restoration procedure.

Factors that are important in surgical decision-making include defect location and size, subchondral bone status, unipolar vs bipolar lesions, and previous cartilage procedure.

Location. The shapes of the patella and trochlea vary much more than the shapes of the condyles and plateaus. This variability complicates morphology matching, particularly with involvement of the central TG and median patellar ridge. Therefore, focal contained lesions of the patella and trochlea may be more technically amenable to cell therapy techniques than to osteochondral procedures, which require contour matching between donor and recipient

Size. Although small lesions in the femoral condyles can be considered for microfracture (MFx) or osteochondral autograft transfer (OAT), MFx is less suitable because of poor results in the PF joint, and OAT because of donor-site morbidity in the trochlea.

Subchondral bone status. When subchondral bone is compromised, such as with bone loss, cysts, or significant bone edema, the entire osteochondral unit should be treated. Here, OAT and osteochondral allograft (OCA) are the preferred treatments, depending on lesion size.

Unipolar vs bipolar lesions. Compared with unipolar lesions, bipolar lesions tend to have worse outcomes. Therefore, an associated unloading procedure (TT osteotomy) should be given special consideration. Autologous chondrocyte implantation (ACI) appears to have better outcomes than OCA for bipolar PF lesions.^9,10

Previous surgery. Although a failed cartilage procedure can negatively affect ACI outcomes, particularly in the presence of intralesional osteophytes,¹¹ it does not affect OCA outcomes.¹² Therefore, after previous MFx, OCA instead of ACI may be considered.

Fragment Fixation

Viable fragments from traumatic lesions (direct trauma or patellar dislocation) or osteochondritis dissecans should be repaired if possible, particularly in young patients. In a fragment that contains a substantial amount of bone, compression screws provide stable fixation. More recently, it has been recognized that fixation of predominantly cartilaginous fragments can be successful¹³ (Figure 1B). Débridement of soft tissue in the lesion bed and on the fragment is important in facilitating healing, as is removal of sclerotic bone.

MFx

Although MFx can have good outcomes in small contained femoral condyle lesions, in the PF joint treatment has been more challenging, and clinical outcomes have been poor (increased subchondral edema, increased effusion).¹⁴ In addition, deterioration becomes significant after 36 months. Therefore, MFx should be restricted to small (<2 cm²), well-contained trochlear defects, particularly in low-demand patients.

ACI and Matrix-Induced ACI

As stated, ACI (Figure 2) is suitable for PF joints because it intrinsically respects the complex anatomy.

OAT

As mentioned, donor-site morbidity may compromise final outcomes of harvest and implantation in the PF joint. Nonetheless, in carefully selected patients with small lesions that are limited to 1 facet (not including the patellar ridge or the TG) and that require only 1 plug (Figure 3), OAT can have good clinical results.¹⁶

OCA

Two techniques can be used with OCA in the PF joint. The dowel technique, in which circular plugs are implanted, is predominantly used for defects that do not cross the midline (those located in their entirety on the medial or lateral aspect of the patella or trochlea). Central defects, which can be treated with the dowel technique as well, are technically more challenging to match perfectly, because of the complex geometry of the median ridge and the TG (Figure 4).

Experimental and Emerging Technologies

Biocartilage

Biocartilage, a dehydrated, micronized allogeneic cartilage scaffold implanted with platelet-rich plasma and fibrin glue added over a contained MFx-treated defect, can be used in the patella and trochlea and has the same indications as MFx (small lesions, contained lesions). There are limited clinical studies of short- or long-term outcomes.

Fresh and Viable OCA

Fresh OCA (ProChondrix; AlloSource) and viable/cryopreserved OCA (Cartiform; Arthrex) are thin osteochondral scaffolds that contain viable chondrocytes and growth factors. They can be implanted alone or used with MFx, and are indicated for lesions measuring 1 cm² to 3 cm². Aside from a case report,¹⁷ there are no clinical studies on outcomes.

Bone Marrow Aspirate Concentrate Implantation

Bone marrow aspirate concentrate from centrifuged iliac crest–harvested aspirate containing mesenchymal stem cells with chondrogenic potential is applied under a synthetic scaffold. Indications are the same as for ACI. Medium-term follow-up studies in the PF joint have shown good results, similar to those obtained with matrix-induced ACI.¹⁸

Particulated Juvenile Allograft Cartilage

Particulated juvenile allograft cartilage (DeNovo NT Graft; Zimmer Biomet) is minced cartilage allograft (from juvenile donors) that has been cut into cubes (~1 mm³). Indications are for patellar and trochlear lesions 1 cm² to 6 cm². For both the trochlea and the patella, short-term outcomes have been good.^19,20

Rehabilitation After Surgery

Isolated PF cartilage restoration generally does not require prolonged weight-bearing restrictions, and ambulation with the knee locked in full extension is permitted as tolerated. Concurrent TT osteotomy, however, requires protection with 4 to 6 weeks of toe-touch weight-bearing to minimize the risk of tibial fracture.

Conclusion

Comprehensive preoperative assessment is essential and should include a thorough core-to-floor physical examination as well as PF-specific imaging. Treatment of symptomatic chondral lesions in the PF joint requires specific technical and postoperative management, which differs significantly from management involving the condyles. Attending to all these details makes the outcomes of PF cartilage treatment reproducible. These outcomes may rival those of condylar treatment.

Take-Home Points

• Careful evaluation is key in attributing knee pain to patellofemoral cartilage lesions-that is, in making a "diagnosis by exclusion".
• Initial treatment is nonoperative management focused on weight loss and extensive "core-to-floor" rehabilitation.
• Optimization of anatomy and biomechanics is crucial.
• Factors important in surgical decision-making incude defect location and size, subchondral bone status, unipolar vs bipolar lesions, and previous cartilage procedure.
• The most commonly used surgical procedures-autologous chondrocyte implantation, osteochondral autograft transfer, and osteochondral allograft-have demonstrated improved intermediate-term outcomes.

Patellofemoral (PF) pain is often a component of more general anterior knee pain. One source of PF pain is chondral lesions. As these lesions are commonly seen on magnetic resonance imaging (MRI) and during arthroscopy, it is necessary to differentiate incidental and symptomatic lesions.¹ In addition, the correlation between symptoms and lesion presence and severity is poor.

PF pain is multifactorial (structural lesions, malalignment, deconditioning, muscle imbalance and overuse) and can coexist with other lesions in the knee (ligament tears, meniscal injuries, and cartilage lesions in other compartments). Therefore, careful evaluation is key in attributing knee pain to PF cartilage lesions—that is, in making a "diagnosis by exclusion."

From the start, it must be appreciated that the vast majority of patients will not require surgery, and many who require surgery for pain will not require cartilage restoration. One key to success with PF patients is a good working relationship with an experienced physical therapist.

Etiology

The primary causes of PF cartilage lesions are patellar instability, chronic maltracking without instability, direct trauma, repetitive microtrauma, and idiopathic.

Patellar Instability

Patients with patellar instability often present with underlying anatomical risk factors (eg, trochlear dysplasia, increased Q-angle/tibial tubercle-trochlear groove [TT-TG] distance, patella alta, and unbalanced medial and lateral soft tissues²). These factors should be addressed before surgery.

Patellar instability can cause cartilage damage during the dislocation event or by chronic subluxation. Cartilage becomes damaged in up to 96% of patellar dislocations.³ Most commonly, the damage consists of fissuring and/or fibrillation, but chondral and osteochondral fractures can occur as well. During dislocation, the medial patella strikes the lateral aspect of the femur, and, as the knee collapses into flexion, the lateral aspect of the proximal lateral femoral condyle (weight-bearing area) can sustain damage. In the patella, typically the injury is distal-medial (occasionally crossing the median ridge). A shear lesion may involve the chondral surface or be osteochondral (Figure 1A).

Chronic Maltracking Without Instability

Chronic maltracking is usually related to anatomical abnormalities, which include the same factors that can cause patellar instability. A common combination is trochlear dysplasia, increased TT-TG or TT-posterior cruciate ligament distance, and lateral soft-tissue contracture. These are often seen in PF joints that progress to lateral PF arthritis. As lateral PF arthritis progresses, lateral soft-tissue contracture worsens, compounding symptoms of laterally based pain. With respect to cartilage repair, these joints can be treated if recognized early; however, once osteoarthritis is fully established in the joint, facetectomy or PF replacement may be necessary.

Direct Trauma

With the knee in flexion during a direct trauma over the patella (eg, fall or dashboard trauma), all zones of cartilage and subchondral bone in both patella and trochlea can be injured, leading to macrostructural damage, chondral/osteochondral fracture, or, with a subcritical force, microstructural damage and chondrocyte death, subsequently causing cartilage degeneration (cartilage may look normal initially; the matrix takes months to years to deteriorate). Direct trauma usually occurs with the knee flexed. Therefore, these lesions typically are located in the distal trochlea and superior pole of the patella.

Repetitive Microtrauma

Minor injuries, which by themselves do not immediately cause apparent chondral or osteochondral fractures, may eventually exceed the capacity of natural cartilage homeostasis and result in repetitive microtrauma. Common causes are repeated jumping (as in basketball and volleyball) and prolonged flexed-knee position (eg, what a baseball catcher experiences), which may also be associated with other lesions caused by extensor apparatus overload (eg, quadriceps tendon or patellar tendon tendinitis, and fat pad impingement syndrome).

Idiopathic

In a subset of patients with osteochondritis dissecans, the patella is the lesion site. In another subset, idiopathic lesions may be related to a genetic predisposition to osteoarthritis and may not be restricted to the PF joint. In some cases, the PF joint is the first compartment to degenerate and is the most symptomatic in a setting of truly tricompartmental disease. In these cases, treating only the PF lesion can result in functional failure, owing to disease progression in other compartments. Even mild disease in other compartments should be carefully evaluated.

History and Physical Examination

Patients often report a history of anterior knee pain that worsens with stair use, prolonged sitting, and flexed-knee activities (eg, squatting). Compared with pain alone, swelling, though not specific to cartilage disease, is more suspicious for a cartilage etiology. Identifying the cartilage defect as the sole source of pain is particularly difficult in patients with recurrent patellar instability. In these patients, pain and swelling, even between instability episodes, suggest that cartilage damage is at least a component of the symptomology.

Important diagnostic components of physical examination are gait analysis, tibiofemoral alignment, and patellar alignment in all 3 planes, both static and functional. Patella-specific measurements include medial-lateral position and quadrants of excursion, lateral tilt, and patella alta, as well as J-sign and subluxation with quadriceps contraction in extension.

It is also important to document effusion; crepitus; active and passive range of motion (spine, hips, knees); site of pain or tenderness to palpation (medial, lateral, distal, retropatellar) and whether it matches the complaints and the location of the cartilage lesion; results of the grind test (placing downward force on the patella during flexion and extension) and whether they match the flexion angle of the tenderness and the flexion angle in which the cartilage lesion has increased PF contact; ligamentous and soft-tissue stability or imbalance (tibiofemoral and patellar; apprehension test, glide test, tilt test); and muscle strength, flexibility, and atrophy of the core (abdomen, dorsal and hip muscles) and lower extremities (quadriceps, hamstrings, gastrocnemius).

Imaging

Imaging should be used to evaluate both PF alignment and the cartilage lesions. For alignment, standard radiographs (weight-bearing knee sequence and axial view; full limb length when needed), computed tomography, and MRI can be used.

Meaningful evaluation requires MRI with cartilage-specific sequences, including standard spin-echo (SE) and gradient-recalled echo (GRE), fast SE, and, for cartilage morphology, T2-weighted fat suppression (FS) and 3-dimensional SE and GRE.⁵ For evaluation of cartilage function and metabolism, the collagen network, and proteoglycan content in the knee cartilage matrix, consideration should be given to compositional assessment techniques, such as T2 mapping, delayed gadolinium-enhanced MRI of cartilage, T1ρ imaging, sodium imaging, and diffusion-weighted sequences.⁵ Use of the latter functional sequences is still debatable, and these sequences are not widely available.

Treatment

In general, the initial approach is nonoperative management focused on weight loss and extensive core-to-floor rehabilitation, unless surgery is specifically indicated (eg, for loose body removal or osteochondral fracture reattachment). Rehabilitation focuses on achieving adequate range of motion of the spine, hips, and knees along with muscle strength and flexibility of the core (abdomen, dorsal and hip muscles) and lower limbs (quadriceps, hamstrings, gastrocnemius). Rehabilitation is not defined by time but rather by development of an optimized soft-tissue envelope that decreases joint reactive forces. The full process can take 6 to 9 months, but there should be some improvement by 3 months.

Corticosteroid, hyaluronic acid,⁶ or platelet-rich plasma⁷ injections can provide temporary relief and facilitate rehabilitation in the setting of pain inhibition. As stand-alone treatment, injections are more suitable for more diffuse degenerative lesions in older and low-demand patients than for focal traumatic lesions in young and high-demand patients.

Surgery is indicated for full-thickness or nearly full-thickness lesions (International Cartilage Repair Society grade 3a or higher) >1 cm² after failed conservative treatment.

Optimization of anatomy and biomechanics is crucial, as persistent abnormalities lead to high rates of failure of cartilage procedures, and correction of those factors results in outcomes similar to those of patients without such abnormal anatomy.⁸ The procedures most commonly used to improve patellar tracking or unloading in the PF compartment are lateral retinacular lengthening and TT transfer: medialization and/or distalization for correction of malalignment, and straight anteriorization or anteromedialization for unloading. These procedures can improve symptoms and function in lateral and distal patellar and trochlear lesions even without the addition of a cartilage restoration procedure.

Factors that are important in surgical decision-making include defect location and size, subchondral bone status, unipolar vs bipolar lesions, and previous cartilage procedure.

Location. The shapes of the patella and trochlea vary much more than the shapes of the condyles and plateaus. This variability complicates morphology matching, particularly with involvement of the central TG and median patellar ridge. Therefore, focal contained lesions of the patella and trochlea may be more technically amenable to cell therapy techniques than to osteochondral procedures, which require contour matching between donor and recipient

Size. Although small lesions in the femoral condyles can be considered for microfracture (MFx) or osteochondral autograft transfer (OAT), MFx is less suitable because of poor results in the PF joint, and OAT because of donor-site morbidity in the trochlea.

Subchondral bone status. When subchondral bone is compromised, such as with bone loss, cysts, or significant bone edema, the entire osteochondral unit should be treated. Here, OAT and osteochondral allograft (OCA) are the preferred treatments, depending on lesion size.

Unipolar vs bipolar lesions. Compared with unipolar lesions, bipolar lesions tend to have worse outcomes. Therefore, an associated unloading procedure (TT osteotomy) should be given special consideration. Autologous chondrocyte implantation (ACI) appears to have better outcomes than OCA for bipolar PF lesions.^9,10

Previous surgery. Although a failed cartilage procedure can negatively affect ACI outcomes, particularly in the presence of intralesional osteophytes,¹¹ it does not affect OCA outcomes.¹² Therefore, after previous MFx, OCA instead of ACI may be considered.

Fragment Fixation

Viable fragments from traumatic lesions (direct trauma or patellar dislocation) or osteochondritis dissecans should be repaired if possible, particularly in young patients. In a fragment that contains a substantial amount of bone, compression screws provide stable fixation. More recently, it has been recognized that fixation of predominantly cartilaginous fragments can be successful¹³ (Figure 1B). Débridement of soft tissue in the lesion bed and on the fragment is important in facilitating healing, as is removal of sclerotic bone.

MFx

Although MFx can have good outcomes in small contained femoral condyle lesions, in the PF joint treatment has been more challenging, and clinical outcomes have been poor (increased subchondral edema, increased effusion).¹⁴ In addition, deterioration becomes significant after 36 months. Therefore, MFx should be restricted to small (<2 cm²), well-contained trochlear defects, particularly in low-demand patients.

ACI and Matrix-Induced ACI

As stated, ACI (Figure 2) is suitable for PF joints because it intrinsically respects the complex anatomy.

OAT

As mentioned, donor-site morbidity may compromise final outcomes of harvest and implantation in the PF joint. Nonetheless, in carefully selected patients with small lesions that are limited to 1 facet (not including the patellar ridge or the TG) and that require only 1 plug (Figure 3), OAT can have good clinical results.¹⁶

OCA

Two techniques can be used with OCA in the PF joint. The dowel technique, in which circular plugs are implanted, is predominantly used for defects that do not cross the midline (those located in their entirety on the medial or lateral aspect of the patella or trochlea). Central defects, which can be treated with the dowel technique as well, are technically more challenging to match perfectly, because of the complex geometry of the median ridge and the TG (Figure 4).

Experimental and Emerging Technologies

Biocartilage

Biocartilage, a dehydrated, micronized allogeneic cartilage scaffold implanted with platelet-rich plasma and fibrin glue added over a contained MFx-treated defect, can be used in the patella and trochlea and has the same indications as MFx (small lesions, contained lesions). There are limited clinical studies of short- or long-term outcomes.

Fresh and Viable OCA

Fresh OCA (ProChondrix; AlloSource) and viable/cryopreserved OCA (Cartiform; Arthrex) are thin osteochondral scaffolds that contain viable chondrocytes and growth factors. They can be implanted alone or used with MFx, and are indicated for lesions measuring 1 cm² to 3 cm². Aside from a case report,¹⁷ there are no clinical studies on outcomes.

Bone Marrow Aspirate Concentrate Implantation

Bone marrow aspirate concentrate from centrifuged iliac crest–harvested aspirate containing mesenchymal stem cells with chondrogenic potential is applied under a synthetic scaffold. Indications are the same as for ACI. Medium-term follow-up studies in the PF joint have shown good results, similar to those obtained with matrix-induced ACI.¹⁸

Particulated Juvenile Allograft Cartilage

Particulated juvenile allograft cartilage (DeNovo NT Graft; Zimmer Biomet) is minced cartilage allograft (from juvenile donors) that has been cut into cubes (~1 mm³). Indications are for patellar and trochlear lesions 1 cm² to 6 cm². For both the trochlea and the patella, short-term outcomes have been good.^19,20

Rehabilitation After Surgery

Isolated PF cartilage restoration generally does not require prolonged weight-bearing restrictions, and ambulation with the knee locked in full extension is permitted as tolerated. Concurrent TT osteotomy, however, requires protection with 4 to 6 weeks of toe-touch weight-bearing to minimize the risk of tibial fracture.

Conclusion

Comprehensive preoperative assessment is essential and should include a thorough core-to-floor physical examination as well as PF-specific imaging. Treatment of symptomatic chondral lesions in the PF joint requires specific technical and postoperative management, which differs significantly from management involving the condyles. Attending to all these details makes the outcomes of PF cartilage treatment reproducible. These outcomes may rival those of condylar treatment.

Take-Home Points

• Careful evaluation is key in attributing knee pain to patellofemoral cartilage lesions-that is, in making a "diagnosis by exclusion".
• Initial treatment is nonoperative management focused on weight loss and extensive "core-to-floor" rehabilitation.
• Optimization of anatomy and biomechanics is crucial.
• Factors important in surgical decision-making incude defect location and size, subchondral bone status, unipolar vs bipolar lesions, and previous cartilage procedure.
• The most commonly used surgical procedures-autologous chondrocyte implantation, osteochondral autograft transfer, and osteochondral allograft-have demonstrated improved intermediate-term outcomes.

Patellofemoral (PF) pain is often a component of more general anterior knee pain. One source of PF pain is chondral lesions. As these lesions are commonly seen on magnetic resonance imaging (MRI) and during arthroscopy, it is necessary to differentiate incidental and symptomatic lesions.¹ In addition, the correlation between symptoms and lesion presence and severity is poor.

PF pain is multifactorial (structural lesions, malalignment, deconditioning, muscle imbalance and overuse) and can coexist with other lesions in the knee (ligament tears, meniscal injuries, and cartilage lesions in other compartments). Therefore, careful evaluation is key in attributing knee pain to PF cartilage lesions—that is, in making a "diagnosis by exclusion."

From the start, it must be appreciated that the vast majority of patients will not require surgery, and many who require surgery for pain will not require cartilage restoration. One key to success with PF patients is a good working relationship with an experienced physical therapist.

Etiology

The primary causes of PF cartilage lesions are patellar instability, chronic maltracking without instability, direct trauma, repetitive microtrauma, and idiopathic.

Patellar Instability

Patients with patellar instability often present with underlying anatomical risk factors (eg, trochlear dysplasia, increased Q-angle/tibial tubercle-trochlear groove [TT-TG] distance, patella alta, and unbalanced medial and lateral soft tissues²). These factors should be addressed before surgery.

Patellar instability can cause cartilage damage during the dislocation event or by chronic subluxation. Cartilage becomes damaged in up to 96% of patellar dislocations.³ Most commonly, the damage consists of fissuring and/or fibrillation, but chondral and osteochondral fractures can occur as well. During dislocation, the medial patella strikes the lateral aspect of the femur, and, as the knee collapses into flexion, the lateral aspect of the proximal lateral femoral condyle (weight-bearing area) can sustain damage. In the patella, typically the injury is distal-medial (occasionally crossing the median ridge). A shear lesion may involve the chondral surface or be osteochondral (Figure 1A).

Chronic Maltracking Without Instability

Chronic maltracking is usually related to anatomical abnormalities, which include the same factors that can cause patellar instability. A common combination is trochlear dysplasia, increased TT-TG or TT-posterior cruciate ligament distance, and lateral soft-tissue contracture. These are often seen in PF joints that progress to lateral PF arthritis. As lateral PF arthritis progresses, lateral soft-tissue contracture worsens, compounding symptoms of laterally based pain. With respect to cartilage repair, these joints can be treated if recognized early; however, once osteoarthritis is fully established in the joint, facetectomy or PF replacement may be necessary.

Direct Trauma

With the knee in flexion during a direct trauma over the patella (eg, fall or dashboard trauma), all zones of cartilage and subchondral bone in both patella and trochlea can be injured, leading to macrostructural damage, chondral/osteochondral fracture, or, with a subcritical force, microstructural damage and chondrocyte death, subsequently causing cartilage degeneration (cartilage may look normal initially; the matrix takes months to years to deteriorate). Direct trauma usually occurs with the knee flexed. Therefore, these lesions typically are located in the distal trochlea and superior pole of the patella.

Repetitive Microtrauma

Minor injuries, which by themselves do not immediately cause apparent chondral or osteochondral fractures, may eventually exceed the capacity of natural cartilage homeostasis and result in repetitive microtrauma. Common causes are repeated jumping (as in basketball and volleyball) and prolonged flexed-knee position (eg, what a baseball catcher experiences), which may also be associated with other lesions caused by extensor apparatus overload (eg, quadriceps tendon or patellar tendon tendinitis, and fat pad impingement syndrome).

Idiopathic

In a subset of patients with osteochondritis dissecans, the patella is the lesion site. In another subset, idiopathic lesions may be related to a genetic predisposition to osteoarthritis and may not be restricted to the PF joint. In some cases, the PF joint is the first compartment to degenerate and is the most symptomatic in a setting of truly tricompartmental disease. In these cases, treating only the PF lesion can result in functional failure, owing to disease progression in other compartments. Even mild disease in other compartments should be carefully evaluated.

History and Physical Examination

Patients often report a history of anterior knee pain that worsens with stair use, prolonged sitting, and flexed-knee activities (eg, squatting). Compared with pain alone, swelling, though not specific to cartilage disease, is more suspicious for a cartilage etiology. Identifying the cartilage defect as the sole source of pain is particularly difficult in patients with recurrent patellar instability. In these patients, pain and swelling, even between instability episodes, suggest that cartilage damage is at least a component of the symptomology.

Important diagnostic components of physical examination are gait analysis, tibiofemoral alignment, and patellar alignment in all 3 planes, both static and functional. Patella-specific measurements include medial-lateral position and quadrants of excursion, lateral tilt, and patella alta, as well as J-sign and subluxation with quadriceps contraction in extension.

It is also important to document effusion; crepitus; active and passive range of motion (spine, hips, knees); site of pain or tenderness to palpation (medial, lateral, distal, retropatellar) and whether it matches the complaints and the location of the cartilage lesion; results of the grind test (placing downward force on the patella during flexion and extension) and whether they match the flexion angle of the tenderness and the flexion angle in which the cartilage lesion has increased PF contact; ligamentous and soft-tissue stability or imbalance (tibiofemoral and patellar; apprehension test, glide test, tilt test); and muscle strength, flexibility, and atrophy of the core (abdomen, dorsal and hip muscles) and lower extremities (quadriceps, hamstrings, gastrocnemius).

Imaging

Imaging should be used to evaluate both PF alignment and the cartilage lesions. For alignment, standard radiographs (weight-bearing knee sequence and axial view; full limb length when needed), computed tomography, and MRI can be used.

Meaningful evaluation requires MRI with cartilage-specific sequences, including standard spin-echo (SE) and gradient-recalled echo (GRE), fast SE, and, for cartilage morphology, T2-weighted fat suppression (FS) and 3-dimensional SE and GRE.⁵ For evaluation of cartilage function and metabolism, the collagen network, and proteoglycan content in the knee cartilage matrix, consideration should be given to compositional assessment techniques, such as T2 mapping, delayed gadolinium-enhanced MRI of cartilage, T1ρ imaging, sodium imaging, and diffusion-weighted sequences.⁵ Use of the latter functional sequences is still debatable, and these sequences are not widely available.

Treatment

In general, the initial approach is nonoperative management focused on weight loss and extensive core-to-floor rehabilitation, unless surgery is specifically indicated (eg, for loose body removal or osteochondral fracture reattachment). Rehabilitation focuses on achieving adequate range of motion of the spine, hips, and knees along with muscle strength and flexibility of the core (abdomen, dorsal and hip muscles) and lower limbs (quadriceps, hamstrings, gastrocnemius). Rehabilitation is not defined by time but rather by development of an optimized soft-tissue envelope that decreases joint reactive forces. The full process can take 6 to 9 months, but there should be some improvement by 3 months.

Corticosteroid, hyaluronic acid,⁶ or platelet-rich plasma⁷ injections can provide temporary relief and facilitate rehabilitation in the setting of pain inhibition. As stand-alone treatment, injections are more suitable for more diffuse degenerative lesions in older and low-demand patients than for focal traumatic lesions in young and high-demand patients.

Surgery is indicated for full-thickness or nearly full-thickness lesions (International Cartilage Repair Society grade 3a or higher) >1 cm² after failed conservative treatment.

Optimization of anatomy and biomechanics is crucial, as persistent abnormalities lead to high rates of failure of cartilage procedures, and correction of those factors results in outcomes similar to those of patients without such abnormal anatomy.⁸ The procedures most commonly used to improve patellar tracking or unloading in the PF compartment are lateral retinacular lengthening and TT transfer: medialization and/or distalization for correction of malalignment, and straight anteriorization or anteromedialization for unloading. These procedures can improve symptoms and function in lateral and distal patellar and trochlear lesions even without the addition of a cartilage restoration procedure.

Factors that are important in surgical decision-making include defect location and size, subchondral bone status, unipolar vs bipolar lesions, and previous cartilage procedure.

Location. The shapes of the patella and trochlea vary much more than the shapes of the condyles and plateaus. This variability complicates morphology matching, particularly with involvement of the central TG and median patellar ridge. Therefore, focal contained lesions of the patella and trochlea may be more technically amenable to cell therapy techniques than to osteochondral procedures, which require contour matching between donor and recipient

Size. Although small lesions in the femoral condyles can be considered for microfracture (MFx) or osteochondral autograft transfer (OAT), MFx is less suitable because of poor results in the PF joint, and OAT because of donor-site morbidity in the trochlea.

Subchondral bone status. When subchondral bone is compromised, such as with bone loss, cysts, or significant bone edema, the entire osteochondral unit should be treated. Here, OAT and osteochondral allograft (OCA) are the preferred treatments, depending on lesion size.

Unipolar vs bipolar lesions. Compared with unipolar lesions, bipolar lesions tend to have worse outcomes. Therefore, an associated unloading procedure (TT osteotomy) should be given special consideration. Autologous chondrocyte implantation (ACI) appears to have better outcomes than OCA for bipolar PF lesions.^9,10

Previous surgery. Although a failed cartilage procedure can negatively affect ACI outcomes, particularly in the presence of intralesional osteophytes,¹¹ it does not affect OCA outcomes.¹² Therefore, after previous MFx, OCA instead of ACI may be considered.

Fragment Fixation

Viable fragments from traumatic lesions (direct trauma or patellar dislocation) or osteochondritis dissecans should be repaired if possible, particularly in young patients. In a fragment that contains a substantial amount of bone, compression screws provide stable fixation. More recently, it has been recognized that fixation of predominantly cartilaginous fragments can be successful¹³ (Figure 1B). Débridement of soft tissue in the lesion bed and on the fragment is important in facilitating healing, as is removal of sclerotic bone.

MFx

Although MFx can have good outcomes in small contained femoral condyle lesions, in the PF joint treatment has been more challenging, and clinical outcomes have been poor (increased subchondral edema, increased effusion).¹⁴ In addition, deterioration becomes significant after 36 months. Therefore, MFx should be restricted to small (<2 cm²), well-contained trochlear defects, particularly in low-demand patients.

ACI and Matrix-Induced ACI

As stated, ACI (Figure 2) is suitable for PF joints because it intrinsically respects the complex anatomy.

OAT

As mentioned, donor-site morbidity may compromise final outcomes of harvest and implantation in the PF joint. Nonetheless, in carefully selected patients with small lesions that are limited to 1 facet (not including the patellar ridge or the TG) and that require only 1 plug (Figure 3), OAT can have good clinical results.¹⁶

OCA

Two techniques can be used with OCA in the PF joint. The dowel technique, in which circular plugs are implanted, is predominantly used for defects that do not cross the midline (those located in their entirety on the medial or lateral aspect of the patella or trochlea). Central defects, which can be treated with the dowel technique as well, are technically more challenging to match perfectly, because of the complex geometry of the median ridge and the TG (Figure 4).

Experimental and Emerging Technologies

Biocartilage

Biocartilage, a dehydrated, micronized allogeneic cartilage scaffold implanted with platelet-rich plasma and fibrin glue added over a contained MFx-treated defect, can be used in the patella and trochlea and has the same indications as MFx (small lesions, contained lesions). There are limited clinical studies of short- or long-term outcomes.

Fresh and Viable OCA

Fresh OCA (ProChondrix; AlloSource) and viable/cryopreserved OCA (Cartiform; Arthrex) are thin osteochondral scaffolds that contain viable chondrocytes and growth factors. They can be implanted alone or used with MFx, and are indicated for lesions measuring 1 cm² to 3 cm². Aside from a case report,¹⁷ there are no clinical studies on outcomes.

Bone Marrow Aspirate Concentrate Implantation

Bone marrow aspirate concentrate from centrifuged iliac crest–harvested aspirate containing mesenchymal stem cells with chondrogenic potential is applied under a synthetic scaffold. Indications are the same as for ACI. Medium-term follow-up studies in the PF joint have shown good results, similar to those obtained with matrix-induced ACI.¹⁸

Particulated Juvenile Allograft Cartilage

Particulated juvenile allograft cartilage (DeNovo NT Graft; Zimmer Biomet) is minced cartilage allograft (from juvenile donors) that has been cut into cubes (~1 mm³). Indications are for patellar and trochlear lesions 1 cm² to 6 cm². For both the trochlea and the patella, short-term outcomes have been good.^19,20

Rehabilitation After Surgery

Isolated PF cartilage restoration generally does not require prolonged weight-bearing restrictions, and ambulation with the knee locked in full extension is permitted as tolerated. Concurrent TT osteotomy, however, requires protection with 4 to 6 weeks of toe-touch weight-bearing to minimize the risk of tibial fracture.

Conclusion

Comprehensive preoperative assessment is essential and should include a thorough core-to-floor physical examination as well as PF-specific imaging. Treatment of symptomatic chondral lesions in the PF joint requires specific technical and postoperative management, which differs significantly from management involving the condyles. Attending to all these details makes the outcomes of PF cartilage treatment reproducible. These outcomes may rival those of condylar treatment.

This spring, the US Food and Drug Administration approved a second cyclin-dependent kinase (CDK) inhibitor for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer in combination with aromatase inhibitors (AIs).¹ The drug, ribociclib, joins palbociclib as the second drug in this class, which targets key regulators of the mammalian cell cycle and can help to overcome resistance to endocrine therapy–like AIs, a standard front-line treatment option in this group of patients. Palbociclib (Ibrance) was approved last year in combination with the AI letrozole, which was recently expanded to include its use in combination with all AIs, the same indication for which ribociclib received approval.

The ribociclib approval was based on the results of a phase 3, randomized, double-blind, placebo-controlled, international clinical trial called MONALEESA-2.² The trial, conducted in 29 countries, compared the effects of ribociclib plus letrozole with letrozole plus placebo in 668 postmenopausal women with locally confirmed, HR-positive, HER2-negative, recurrent or metastatic breast cancer.

Patients had not received previous systemic therapy for advanced disease, had measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), had an Eastern Cooperative Oncology Group performance status of 0 or 1 (range, 1-5; 0, fully active and 5, dead), and had adequate bone marrow and organ function.

Patients were excluded if they had received previous CDK4/6 therapy, any previous systemic chemotherapy, endocrine therapy for advanced disease, previous neoadjuvant or adjuvant therapy with any nonsteroidal AI (unless they had been disease free for more than 12 months), and had inflammatory breast cancer, central nervous system metastases, history of cardiac disease or dysfunction, or impaired gastrointestinal function that alters drug absorption.

Patients were treated with ribociclib at a dose of 600 mg daily on a 3-weeks-on, 1-week-off schedule in 28-day cycles or placebo, which were combined with letrozole at a dose of 2.5 mg a day on a continuous schedule. Randomization was stratified according to the presence or absence of liver or lung metastases and treatment was continued until disease progression, unacceptable toxicity, death or discontinuation of treatment. Dose reductions of ribociclib were allowed, to manage adverse events (AEs), but treatment crossover was not permitted.

Tumor assessments were performed at screening, every 8 weeks during the first 18 months, every 12 weeks thereafter until disease progression, and at the end of treatment, and were assessed by an independent review committee. The baseline characteristics of the patient population were well balanced; patients had a median age of 62 years, all were HR positive except 1 patient who was HER2 positive.

The trial was ended prematurely after an initial interim analysis demonstrated a significant benefit in favor of ribociclib in the primary endpoint, progression-free survival (PFS). Over a median duration of follow-up of 15.3 months, the median PFS was not yet reached in the ribociclib arm, compared with 14.7 months in the placebo arm (hazard ratio, 0.556; P < .0001). In a subsequent analysis with 11 months of additional follow-up, the median PFS was 25.3 months in the combination arm, compared with 16 months in the placebo arm, which translated into a 44% reduction in the risk of disease progression or death. The PFS benefit with ribociclib was observed across all preplanned subgroup analyses. The objective response rates were 52.7% in the ribociclib arm, compared with 37.1% in the placebo arm, but overall survival data were immature.

The frequency and severity of AEs were increased in the combination arm; most common were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. The most common grade 3 or 4 AEs experienced with ribociclib were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting.

Ribociclib is accompanied by warnings and precautions about QT interval prolongation, hepatobiliary toxicity, and neutropenia. Clinicians are advised to monitor electrocardiograms and electrolytes before the start of ribociclib therapy and to begin treatment only in patients with QTcF values <450 ms and in whom electrolyte abnormalities have been corrected. ECG should be repeated at around day 14 of the first cycle, the beginning of the second cycle, and as deemed clinically necessary.

Liver function tests should be performed before starting treatment, every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, and as clinically indicated. For aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels greater than 3-5 times the upper limit of normal (ULN, grade 2), ribociclib should be interrupted until recovery to baseline or lower. For levels >5-20 times the ULN (grade 3) or recurring grade 2 increases, treatment should be interrupted until recovery to baseline or lower and then resumed at the next lowest dose level. Treatment with ribociclib should be discontinued in the event of recurring grade 3 elevations or for AST/ALT elevations >3 times ULN in combination with total bilirubin >2 times ULN.

Complete blood counts should be performed before starting treatment and monitored every 2 weeks for the first 2 cycles, at the beginning of each of the 4 subsequent cycles, and as clinically needed. If absolute neutrophil counts are 500-1,000 mm³ (grade 3), treatment should be discontinued until recovery to grade 2 or lower. If grade 3 neutropenia recurs or for grade 3 febrile neutropenia or grade 4 neutropenia, treatment should resume at a lower dose level upon recovery to grade 2 or lower.

Pregnant women and those of reproductive age should be warned of the risk of fetal harm and the need for effective contraception during treatment and for at least 3 weeks after the last dose. Ribociclib is marketed as Kisqali by Novartis.

This spring, the US Food and Drug Administration approved a second cyclin-dependent kinase (CDK) inhibitor for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer in combination with aromatase inhibitors (AIs).¹ The drug, ribociclib, joins palbociclib as the second drug in this class, which targets key regulators of the mammalian cell cycle and can help to overcome resistance to endocrine therapy–like AIs, a standard front-line treatment option in this group of patients. Palbociclib (Ibrance) was approved last year in combination with the AI letrozole, which was recently expanded to include its use in combination with all AIs, the same indication for which ribociclib received approval.

The ribociclib approval was based on the results of a phase 3, randomized, double-blind, placebo-controlled, international clinical trial called MONALEESA-2.² The trial, conducted in 29 countries, compared the effects of ribociclib plus letrozole with letrozole plus placebo in 668 postmenopausal women with locally confirmed, HR-positive, HER2-negative, recurrent or metastatic breast cancer.

Patients had not received previous systemic therapy for advanced disease, had measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), had an Eastern Cooperative Oncology Group performance status of 0 or 1 (range, 1-5; 0, fully active and 5, dead), and had adequate bone marrow and organ function.

Patients were excluded if they had received previous CDK4/6 therapy, any previous systemic chemotherapy, endocrine therapy for advanced disease, previous neoadjuvant or adjuvant therapy with any nonsteroidal AI (unless they had been disease free for more than 12 months), and had inflammatory breast cancer, central nervous system metastases, history of cardiac disease or dysfunction, or impaired gastrointestinal function that alters drug absorption.

Patients were treated with ribociclib at a dose of 600 mg daily on a 3-weeks-on, 1-week-off schedule in 28-day cycles or placebo, which were combined with letrozole at a dose of 2.5 mg a day on a continuous schedule. Randomization was stratified according to the presence or absence of liver or lung metastases and treatment was continued until disease progression, unacceptable toxicity, death or discontinuation of treatment. Dose reductions of ribociclib were allowed, to manage adverse events (AEs), but treatment crossover was not permitted.

Tumor assessments were performed at screening, every 8 weeks during the first 18 months, every 12 weeks thereafter until disease progression, and at the end of treatment, and were assessed by an independent review committee. The baseline characteristics of the patient population were well balanced; patients had a median age of 62 years, all were HR positive except 1 patient who was HER2 positive.

The trial was ended prematurely after an initial interim analysis demonstrated a significant benefit in favor of ribociclib in the primary endpoint, progression-free survival (PFS). Over a median duration of follow-up of 15.3 months, the median PFS was not yet reached in the ribociclib arm, compared with 14.7 months in the placebo arm (hazard ratio, 0.556; P < .0001). In a subsequent analysis with 11 months of additional follow-up, the median PFS was 25.3 months in the combination arm, compared with 16 months in the placebo arm, which translated into a 44% reduction in the risk of disease progression or death. The PFS benefit with ribociclib was observed across all preplanned subgroup analyses. The objective response rates were 52.7% in the ribociclib arm, compared with 37.1% in the placebo arm, but overall survival data were immature.

The frequency and severity of AEs were increased in the combination arm; most common were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. The most common grade 3 or 4 AEs experienced with ribociclib were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting.

Ribociclib is accompanied by warnings and precautions about QT interval prolongation, hepatobiliary toxicity, and neutropenia. Clinicians are advised to monitor electrocardiograms and electrolytes before the start of ribociclib therapy and to begin treatment only in patients with QTcF values <450 ms and in whom electrolyte abnormalities have been corrected. ECG should be repeated at around day 14 of the first cycle, the beginning of the second cycle, and as deemed clinically necessary.

Liver function tests should be performed before starting treatment, every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, and as clinically indicated. For aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels greater than 3-5 times the upper limit of normal (ULN, grade 2), ribociclib should be interrupted until recovery to baseline or lower. For levels >5-20 times the ULN (grade 3) or recurring grade 2 increases, treatment should be interrupted until recovery to baseline or lower and then resumed at the next lowest dose level. Treatment with ribociclib should be discontinued in the event of recurring grade 3 elevations or for AST/ALT elevations >3 times ULN in combination with total bilirubin >2 times ULN.

Complete blood counts should be performed before starting treatment and monitored every 2 weeks for the first 2 cycles, at the beginning of each of the 4 subsequent cycles, and as clinically needed. If absolute neutrophil counts are 500-1,000 mm³ (grade 3), treatment should be discontinued until recovery to grade 2 or lower. If grade 3 neutropenia recurs or for grade 3 febrile neutropenia or grade 4 neutropenia, treatment should resume at a lower dose level upon recovery to grade 2 or lower.

Pregnant women and those of reproductive age should be warned of the risk of fetal harm and the need for effective contraception during treatment and for at least 3 weeks after the last dose. Ribociclib is marketed as Kisqali by Novartis.

This spring, the US Food and Drug Administration approved a second cyclin-dependent kinase (CDK) inhibitor for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer in combination with aromatase inhibitors (AIs).¹ The drug, ribociclib, joins palbociclib as the second drug in this class, which targets key regulators of the mammalian cell cycle and can help to overcome resistance to endocrine therapy–like AIs, a standard front-line treatment option in this group of patients. Palbociclib (Ibrance) was approved last year in combination with the AI letrozole, which was recently expanded to include its use in combination with all AIs, the same indication for which ribociclib received approval.

The ribociclib approval was based on the results of a phase 3, randomized, double-blind, placebo-controlled, international clinical trial called MONALEESA-2.² The trial, conducted in 29 countries, compared the effects of ribociclib plus letrozole with letrozole plus placebo in 668 postmenopausal women with locally confirmed, HR-positive, HER2-negative, recurrent or metastatic breast cancer.

Patients had not received previous systemic therapy for advanced disease, had measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), had an Eastern Cooperative Oncology Group performance status of 0 or 1 (range, 1-5; 0, fully active and 5, dead), and had adequate bone marrow and organ function.

Patients were excluded if they had received previous CDK4/6 therapy, any previous systemic chemotherapy, endocrine therapy for advanced disease, previous neoadjuvant or adjuvant therapy with any nonsteroidal AI (unless they had been disease free for more than 12 months), and had inflammatory breast cancer, central nervous system metastases, history of cardiac disease or dysfunction, or impaired gastrointestinal function that alters drug absorption.

Patients were treated with ribociclib at a dose of 600 mg daily on a 3-weeks-on, 1-week-off schedule in 28-day cycles or placebo, which were combined with letrozole at a dose of 2.5 mg a day on a continuous schedule. Randomization was stratified according to the presence or absence of liver or lung metastases and treatment was continued until disease progression, unacceptable toxicity, death or discontinuation of treatment. Dose reductions of ribociclib were allowed, to manage adverse events (AEs), but treatment crossover was not permitted.

Tumor assessments were performed at screening, every 8 weeks during the first 18 months, every 12 weeks thereafter until disease progression, and at the end of treatment, and were assessed by an independent review committee. The baseline characteristics of the patient population were well balanced; patients had a median age of 62 years, all were HR positive except 1 patient who was HER2 positive.

The trial was ended prematurely after an initial interim analysis demonstrated a significant benefit in favor of ribociclib in the primary endpoint, progression-free survival (PFS). Over a median duration of follow-up of 15.3 months, the median PFS was not yet reached in the ribociclib arm, compared with 14.7 months in the placebo arm (hazard ratio, 0.556; P < .0001). In a subsequent analysis with 11 months of additional follow-up, the median PFS was 25.3 months in the combination arm, compared with 16 months in the placebo arm, which translated into a 44% reduction in the risk of disease progression or death. The PFS benefit with ribociclib was observed across all preplanned subgroup analyses. The objective response rates were 52.7% in the ribociclib arm, compared with 37.1% in the placebo arm, but overall survival data were immature.

The frequency and severity of AEs were increased in the combination arm; most common were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. The most common grade 3 or 4 AEs experienced with ribociclib were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting.

Ribociclib is accompanied by warnings and precautions about QT interval prolongation, hepatobiliary toxicity, and neutropenia. Clinicians are advised to monitor electrocardiograms and electrolytes before the start of ribociclib therapy and to begin treatment only in patients with QTcF values <450 ms and in whom electrolyte abnormalities have been corrected. ECG should be repeated at around day 14 of the first cycle, the beginning of the second cycle, and as deemed clinically necessary.

Liver function tests should be performed before starting treatment, every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, and as clinically indicated. For aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels greater than 3-5 times the upper limit of normal (ULN, grade 2), ribociclib should be interrupted until recovery to baseline or lower. For levels >5-20 times the ULN (grade 3) or recurring grade 2 increases, treatment should be interrupted until recovery to baseline or lower and then resumed at the next lowest dose level. Treatment with ribociclib should be discontinued in the event of recurring grade 3 elevations or for AST/ALT elevations >3 times ULN in combination with total bilirubin >2 times ULN.

Complete blood counts should be performed before starting treatment and monitored every 2 weeks for the first 2 cycles, at the beginning of each of the 4 subsequent cycles, and as clinically needed. If absolute neutrophil counts are 500-1,000 mm³ (grade 3), treatment should be discontinued until recovery to grade 2 or lower. If grade 3 neutropenia recurs or for grade 3 febrile neutropenia or grade 4 neutropenia, treatment should resume at a lower dose level upon recovery to grade 2 or lower.

Pregnant women and those of reproductive age should be warned of the risk of fetal harm and the need for effective contraception during treatment and for at least 3 weeks after the last dose. Ribociclib is marketed as Kisqali by Novartis.

When the US Food and Drug Administration approved olaratumab as a first-line treatment for patients with soft tissue sarcoma (STS) in the fall of 2016, it marked the first approval since the chemotherapy drug doxorubicin became standard of care more than 40 years ago.¹ Though rare, STS, which comprises a host of different histologic subtypes, has proven difficult to treat. Like pazopanib, which was approved in 2012 for the treatment of STS in the second-line setting, olaratumab targets the platelet-derived growth factor receptor alpha (PDGFRα), a tyrosine kinase receptor involved in cell signaling pathways that promotes key hallmark abilities in both cancer cells and the cells of the tumor microenvironment. Olaratumab, however, is a much more specific inhibitor of PDGFRα compared with pazopanib.

Accelerated approval was granted for the treatment of patients with STS that is not amenable to curative treatment with radiotherapy or surgery and with a subtype that cannot be treated effectively with an anthracycline-containing regimen. The approval was based on the phase 2 JGDG study, a randomized, active-controlled clinical trial in which 133 patients were randomized 1:1 to receive olaratumab plus doxorubicin, or doxorubicin alone.²

Eligible patients included those aged 18 years and over, with histologically confirmed diagnosis of locally advanced or metastatic STS not previously treated with an anthracycline, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (range, 1-5; 0, fully active and 5, dead), and with available tumor tissue for determination of PDGFRα expression by immunohistochemistry. Patients were enrolled at 16 clinical sites in 16 cities and 15 states in the United States from October 2010 to January 2013.

Patients were excluded if they had histologically or cytologically confirmed Kaposi sarcoma; untreated central nervous system metastases; received prior treatment with doxorubicin or other anthracyclines and anthracenediones, or any drug targeting PDGF or the PDGFRs; received concurrent treatment with other anticancer therapy within 4 weeks before study entry; unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction within 6 months before study entry; HIV infection; or if they were pregnant or lactating.

Olaratumab was administered at 15 mg/kg as an intravenous infusion on days 1 and 8 of each 21-day cycle, and doxorubicin at 75 mg/m² as an intravenous infusion on day 1 of each cycle, for a maximum of 8 cycles. Patients were permitted to receive dexarozoxane on cycles 5-8 and crossover was permitted. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 6 weeks, and survival assessed every 2 months, until study completion. PDGFR expression was assessed by immunohistochemistry at a central academic laboratory before randomization.

The primary endpoint of the study was progression-free survival (PFS) and the combination of olaratumab–doxorubicin significantly extended PFS in this patient population: median PFS was 6.6 months in the combination arm, compared with 4.1 months in the doxorubicin-alone arm (hazard ratio [HR], 0.672; P = .0615). The objective response rate (ORR) and median overall survival (OS), which were secondary endpoints in the trial, were also significantly improved with combination therapy compared with doxorubicin alone (ORR, 18.2% vs 11.9%, respectively; median OS, 26.5 months vs 14.7 months). The benefits of combination therapy were observed across prespecified subgroups, including histological tumor type, number of previous treatments, and PDGFRα expression level.

The most common adverse events (AEs) in the patients taking olaratumab were nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache. Grade 3/4 AEs were also higher for the combination than for doxorubicin alone. The most common AE leading to discontinuation of olaratumab was infusion-related reactions, which occurred in 13% of patients.

According to the prescribing information, the recommended dose for olaratumab is 15 mg/kg as an intravenous infusion over 60 minutes on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity, in combination with doxorubicin for the first 8 cycles. Patients should be premedicated with dexamethasone and diphenhydramine, to help protect against infusion-related reactions.

Olaratumab, marketed as Lartruvo by Lilly Oncology, has warnings and precautions relating to infusion-related reactions and embryofetal toxicity. Patients should be monitored for signs and symptoms of the former during and after infusion and olaratumab should be administered in a setting with available resuscitation equipment. Olaratumab should be permanently discontinued in the event of grade 3/4 infusion-related reactions. Olaratumab can cause fetal harm and female patients should be advised of the potential risk to a fetus and the need for effective contraception during treatment and for 3 months after the last dose.

When the US Food and Drug Administration approved olaratumab as a first-line treatment for patients with soft tissue sarcoma (STS) in the fall of 2016, it marked the first approval since the chemotherapy drug doxorubicin became standard of care more than 40 years ago.¹ Though rare, STS, which comprises a host of different histologic subtypes, has proven difficult to treat. Like pazopanib, which was approved in 2012 for the treatment of STS in the second-line setting, olaratumab targets the platelet-derived growth factor receptor alpha (PDGFRα), a tyrosine kinase receptor involved in cell signaling pathways that promotes key hallmark abilities in both cancer cells and the cells of the tumor microenvironment. Olaratumab, however, is a much more specific inhibitor of PDGFRα compared with pazopanib.

Accelerated approval was granted for the treatment of patients with STS that is not amenable to curative treatment with radiotherapy or surgery and with a subtype that cannot be treated effectively with an anthracycline-containing regimen. The approval was based on the phase 2 JGDG study, a randomized, active-controlled clinical trial in which 133 patients were randomized 1:1 to receive olaratumab plus doxorubicin, or doxorubicin alone.²

Eligible patients included those aged 18 years and over, with histologically confirmed diagnosis of locally advanced or metastatic STS not previously treated with an anthracycline, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (range, 1-5; 0, fully active and 5, dead), and with available tumor tissue for determination of PDGFRα expression by immunohistochemistry. Patients were enrolled at 16 clinical sites in 16 cities and 15 states in the United States from October 2010 to January 2013.

Patients were excluded if they had histologically or cytologically confirmed Kaposi sarcoma; untreated central nervous system metastases; received prior treatment with doxorubicin or other anthracyclines and anthracenediones, or any drug targeting PDGF or the PDGFRs; received concurrent treatment with other anticancer therapy within 4 weeks before study entry; unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction within 6 months before study entry; HIV infection; or if they were pregnant or lactating.

Olaratumab was administered at 15 mg/kg as an intravenous infusion on days 1 and 8 of each 21-day cycle, and doxorubicin at 75 mg/m² as an intravenous infusion on day 1 of each cycle, for a maximum of 8 cycles. Patients were permitted to receive dexarozoxane on cycles 5-8 and crossover was permitted. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 6 weeks, and survival assessed every 2 months, until study completion. PDGFR expression was assessed by immunohistochemistry at a central academic laboratory before randomization.

The primary endpoint of the study was progression-free survival (PFS) and the combination of olaratumab–doxorubicin significantly extended PFS in this patient population: median PFS was 6.6 months in the combination arm, compared with 4.1 months in the doxorubicin-alone arm (hazard ratio [HR], 0.672; P = .0615). The objective response rate (ORR) and median overall survival (OS), which were secondary endpoints in the trial, were also significantly improved with combination therapy compared with doxorubicin alone (ORR, 18.2% vs 11.9%, respectively; median OS, 26.5 months vs 14.7 months). The benefits of combination therapy were observed across prespecified subgroups, including histological tumor type, number of previous treatments, and PDGFRα expression level.

The most common adverse events (AEs) in the patients taking olaratumab were nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache. Grade 3/4 AEs were also higher for the combination than for doxorubicin alone. The most common AE leading to discontinuation of olaratumab was infusion-related reactions, which occurred in 13% of patients.

According to the prescribing information, the recommended dose for olaratumab is 15 mg/kg as an intravenous infusion over 60 minutes on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity, in combination with doxorubicin for the first 8 cycles. Patients should be premedicated with dexamethasone and diphenhydramine, to help protect against infusion-related reactions.

Olaratumab, marketed as Lartruvo by Lilly Oncology, has warnings and precautions relating to infusion-related reactions and embryofetal toxicity. Patients should be monitored for signs and symptoms of the former during and after infusion and olaratumab should be administered in a setting with available resuscitation equipment. Olaratumab should be permanently discontinued in the event of grade 3/4 infusion-related reactions. Olaratumab can cause fetal harm and female patients should be advised of the potential risk to a fetus and the need for effective contraception during treatment and for 3 months after the last dose.

When the US Food and Drug Administration approved olaratumab as a first-line treatment for patients with soft tissue sarcoma (STS) in the fall of 2016, it marked the first approval since the chemotherapy drug doxorubicin became standard of care more than 40 years ago.¹ Though rare, STS, which comprises a host of different histologic subtypes, has proven difficult to treat. Like pazopanib, which was approved in 2012 for the treatment of STS in the second-line setting, olaratumab targets the platelet-derived growth factor receptor alpha (PDGFRα), a tyrosine kinase receptor involved in cell signaling pathways that promotes key hallmark abilities in both cancer cells and the cells of the tumor microenvironment. Olaratumab, however, is a much more specific inhibitor of PDGFRα compared with pazopanib.

Accelerated approval was granted for the treatment of patients with STS that is not amenable to curative treatment with radiotherapy or surgery and with a subtype that cannot be treated effectively with an anthracycline-containing regimen. The approval was based on the phase 2 JGDG study, a randomized, active-controlled clinical trial in which 133 patients were randomized 1:1 to receive olaratumab plus doxorubicin, or doxorubicin alone.²

Eligible patients included those aged 18 years and over, with histologically confirmed diagnosis of locally advanced or metastatic STS not previously treated with an anthracycline, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (range, 1-5; 0, fully active and 5, dead), and with available tumor tissue for determination of PDGFRα expression by immunohistochemistry. Patients were enrolled at 16 clinical sites in 16 cities and 15 states in the United States from October 2010 to January 2013.

Patients were excluded if they had histologically or cytologically confirmed Kaposi sarcoma; untreated central nervous system metastases; received prior treatment with doxorubicin or other anthracyclines and anthracenediones, or any drug targeting PDGF or the PDGFRs; received concurrent treatment with other anticancer therapy within 4 weeks before study entry; unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction within 6 months before study entry; HIV infection; or if they were pregnant or lactating.

Olaratumab was administered at 15 mg/kg as an intravenous infusion on days 1 and 8 of each 21-day cycle, and doxorubicin at 75 mg/m² as an intravenous infusion on day 1 of each cycle, for a maximum of 8 cycles. Patients were permitted to receive dexarozoxane on cycles 5-8 and crossover was permitted. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 6 weeks, and survival assessed every 2 months, until study completion. PDGFR expression was assessed by immunohistochemistry at a central academic laboratory before randomization.

The primary endpoint of the study was progression-free survival (PFS) and the combination of olaratumab–doxorubicin significantly extended PFS in this patient population: median PFS was 6.6 months in the combination arm, compared with 4.1 months in the doxorubicin-alone arm (hazard ratio [HR], 0.672; P = .0615). The objective response rate (ORR) and median overall survival (OS), which were secondary endpoints in the trial, were also significantly improved with combination therapy compared with doxorubicin alone (ORR, 18.2% vs 11.9%, respectively; median OS, 26.5 months vs 14.7 months). The benefits of combination therapy were observed across prespecified subgroups, including histological tumor type, number of previous treatments, and PDGFRα expression level.

The most common adverse events (AEs) in the patients taking olaratumab were nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache. Grade 3/4 AEs were also higher for the combination than for doxorubicin alone. The most common AE leading to discontinuation of olaratumab was infusion-related reactions, which occurred in 13% of patients.

According to the prescribing information, the recommended dose for olaratumab is 15 mg/kg as an intravenous infusion over 60 minutes on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity, in combination with doxorubicin for the first 8 cycles. Patients should be premedicated with dexamethasone and diphenhydramine, to help protect against infusion-related reactions.

Olaratumab, marketed as Lartruvo by Lilly Oncology, has warnings and precautions relating to infusion-related reactions and embryofetal toxicity. Patients should be monitored for signs and symptoms of the former during and after infusion and olaratumab should be administered in a setting with available resuscitation equipment. Olaratumab should be permanently discontinued in the event of grade 3/4 infusion-related reactions. Olaratumab can cause fetal harm and female patients should be advised of the potential risk to a fetus and the need for effective contraception during treatment and for 3 months after the last dose.

Study Overview

Objective. To evaluate the effectiveness of OASIS, a large-scale, statewide communication training program, on the reduction of antipsychotic use in nursing homes (NHs).

Design. Quasi-experimental longitudinal study with external controls.

Setting and participants. The participants were residents living in NHs between 1 March 2011 and 31 August 2013. The intervention group consisted of NHs in Massachusetts that were enrolled in the OASIS intervention and the control group consisted of NHs in Massachusetts and New York. The Centers for Medicare & Medicaid Services Minimum Data Set (MDS) 3.0 data was analyzed to determine medication use and behavior of residents of NHs. Residents of these NHs were excluded if they had a US Food and Drug Administration (FDA)-approved indication for antipsychotic use (eg, schizophrenia); were short-term residents (length of stay < 90 days); or had missing data on psychopharmacological medication use or behavior.

Intervention. The OASIS is an educational program that targeted both direct care and non-direct care staff in NHs to assist them in meeting the needs and challenges of caring for long-term care residents. Utilizing a train-the-trainer model, OASIS program coordinators and champions from each intervention NH participated in an 8-hour in-person training session that focused on enhancing communication skills between NH staff and residents with cognitive impairment. These trainers subsequently instructed the OASIS program to staff at their respective NHs using a team-based care approach. Addi-tional support of the OASIS educational program, such as telephone support, 12 webinars, 2 regional seminars, and 2 booster sessions, were provided to participating NHs.

Main outcome measures. The main outcome measure was facility-level prevalence of antipsychotic use in long-term NH residents captured by MDS in the 7 days preceding the MDS assessment. The secondary outcome measures were facility-level quarterly prevalence of psychotropic medications that may have been substituted for antipsychotic medications (ie, anxiolytics, antidepressants, and hypnotics) and behavioral disturbances (ie, physically abusive behavior, verbally abusive behavior, and rejecting care). All secondary outcomes were dichotomized in the 7 days preceding the MDS assessment and aggregated at the facility level for each quarter.

The analysis utilized an interrupted time series model of facility-level prevalence of antipsychotic medication use, other psychotropic medication use, and behavioral disturbances to evaluate the OASIS intervention’s effectiveness in participating facilities compared with control NHs. This methodology allowed the assessment of changes in the trend of antipsychotic use after the OASIS intervention controlling for historical trends. Data from the 18-month pre-intervention (baseline) period was compared with that of a 3-month training phase, a 6-month implementation phase, and a 3-month maintenance phase.

Main results. 93 NHs received OASIS intervention (27 with high prevalence of antipsychotic use) while 831 NHs did not (non-intervention control). The intervention NHs had a higher prevalence of antipsychotic use before OASIS training (baseline period) than the control NHs (34.1% vs. 22.7%, P < 0.001). The intervention NHs compared to controls were smaller in size (122 beds [interquartile range {IQR}, 88–152 beds] vs. 140 beds; [IQR, 104–200 beds]; P < 0.001), more likely to be for profit (77.4% vs. 62.0%, P = 0.009), had corporate ownership (93.5% vs. 74.6%, P < 0.001), and provided resident-only councils (78.5% vs. 52.9%, P < 0.001). The intervention NHs had higher registered nurse (RN) staffing hours per resident (0.8 vs. 0.7; P = 0.01) but lower certified nursing assistant (CNA) hours per resident (2.3 vs. 2.4; P = 0.04) than control NHs. There was no difference in licensed practical nurse hours per resident between groups.

All 93 intervention NHs completed the 8-hour in-person training session and attended an average of 6.5 (range, 0–12) subsequent support webinars. Thirteen NHs (14.0%) attended no regional seminars, 32 (34.4%) attended one, and 48 (51.6%) attended both. Four NHs (4.3%) attended one booster session, and 13 (14.0%) attended both. The NH staff most often trained in the OASIS training program were the directors of nursing, RNs, CNAs, and activities personnel. Support staff including housekeeping and dietary were trained in about half of the reporting intervention NHs, while physicians and nurse practitioners participated infrequently. Concurrent training programs in dementia care (Hand-in-Hand, Alzheimer Association training, MassPRO dementia care training) were implemented in 67.2% of intervention NHs.

In the intervention NHs, the prevalence of antipsych-otic prescribing decreased from 34.1% at baseline to 26.5% at the study end (7.6% absolute reduction, 22.3% relative reduction). In comparison, the prevalence of antipsychotic prescribing in control NHs decreased from 22.7% to 18.8% over the same period (3.9% absolute reduction, 17.2% relative reduction). During the OASIS implementation phase, the intervention NHs had a reduc-tion in prevalence of antipsychotic use (–1.20% [95% confidence interval {CI}, –1.85% to –0.09% per quarter]) greater than that of the control NHs (–0.23% [95% CI, –0.47% to 0.01% per quarter]), resulting in a net OASIS influence of –0.97% (95% CI, –1.85% to –0.09% per quarter; P = 0.03). The antipsychotic use reduction observed in the implementation phase was not sustained in the maintenance phase (difference of 0.93%; 95% CI, –0.66% to 2.54%; P = 0.48). No increases in other psychotropic medication use (anxiolytics, antidepressants, hypnotics) or behavioral disturbances (physically abusive behavior, verbally abusive behavior, and rejecting care) were observed during the OASIS training and implementation phases.

Conclusion. The OASIS communication training program reduced the prevalence of antipsychotic use in NHs during its implementation phase, but its effect was not sustained in the subsequent maintenance phase. The use of other psychotropic medications and behavior disturbances did not increase during the implementation of OASIS program. The findings from this study provided further support for utilizing nonpharmacologic programs to treat behavioral and psychological symptoms of dementia in older adults who reside in NHs.

Commentary

The use of both conventional and atypical antipsychotic medications is associated with a dose-related, approximately 2-fold increased risk of sudden cardiac death in older adults [1,2]. In 2006, the FDA issued a public health advisory stating that both conventional and atypical anti-psychotic medications are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. Despite this black box warning and growing recognition that antipsychotic medications are not indicated for the treatment of dementia-related psychosis, the off-label use of antipsychotic medications to treat behavioral and psychological symptoms of dementia in older adults remains a common practice in nursing homes [3]. Thus, there is an urgent need to assess and develop effective interventions that reduce the practice of antipsychotic medication prescribing in long-term care. To that effect, the study reported by Tjia et al appropriately investigated the impact of the OASIS communication training program, a nonpharmacologic intervention, on the reduction of antipsychotic use in NHs.

This study was well designed and had a number of strengths. It utilized an interrupted time series model, one of the strongest quasi-experimental approaches due to its robustness to threats of internal validity, for evaluating longitudinal effects of an intervention intended to improve the quality of medication use. Moreover, this study included a large sample size and comparison facilities from the same geographical areas (NHs in Massachusetts and New York State) that served as external controls. Several potential weaknesses of the study were identified. Because facility-level aggregate data from NHs were used for analysis, individual level (long-term care resident) characteristics were not accounted for in the analysis. In addition, while the post-OASIS intervention questionnaire response rate was 65.6% (61 of 93 intervention NHs), a higher response rate would provide better characterization of NH staff that participated in OASIS program training, program completion rate, and a more complete representation of competing dementia care training programs concurrently implemented in these NHs.

Several studies, most utilizing various provider education methods, had explored whether these interventions could curb antipsychotic use in NHs with limited success. The largest successful intervention was reported by Meador et al [4], where a focused provider education program facilitated a relative reduction in antipsychotic medication use of 23% compared to control NHs. However, the implementation of this specific program was time- and resource-intensive, requiring geropsychiatry evaluation to all physicians (45 to 60 min), nurse-educator in-service programs for NH staff (5 to 6 one-hr sessions), management specialist consultation to NH administrators (4 hr), and evening meeting for the families of NH residents. The current study by Tjia et al, the largest study to date conducted in the context of competing dementia care training programs and increased awareness of the danger of antipsychotic use in the elderly, similarly showed a meaningful reduction in antipsychotic medication use in NHs that received the OASIS communication training program. The OASIS program appears to be less resource-intensive than the provider education program modeled by Meador et al, and its train-the-trainer model is likely more adaptable to meet the limitations (eg, low staffing and staff turnover) inherent in NHs. The beneficial effect of the OASIS program on reduction of antipsychotic medication prescribing was observed despite low participation by prescribers (11.5% of physicians and 11.5% of nurse practitioners). Although it is unclear why this was observed, this finding is intriguing in that a communication training program that reframes challenging behavior of NH residents with cognitive impairment as (1) communication of unmet needs, (2) train staff to anticipate resident needs, and (3) integrate resident strengths into daily care plans can alter provider prescription behavior. The implication of this is that provider practice in managing behavioral and psychological symptoms of dementia can be improved by optimizing communication training in NH staff. Taken together, this study adds to evidence in favor of utilizing nonpharmacologic interventions to reduce antipsychotic use in long-term care.

Applications for Clinical Practice

OASIS, a communication training program for NH staff, reduces antipsychotic medication use in NHs during its implementation phase. Future studies need to investigate pragmatic methods to sustain the beneficial effect of OASIS after its implementation phase.

—Fred Ko, MD, MS, Icahn School of Medicine at Mount Sinai, New York, NY

Study Overview

Objective. To evaluate the effectiveness of OASIS, a large-scale, statewide communication training program, on the reduction of antipsychotic use in nursing homes (NHs).

Design. Quasi-experimental longitudinal study with external controls.

Setting and participants. The participants were residents living in NHs between 1 March 2011 and 31 August 2013. The intervention group consisted of NHs in Massachusetts that were enrolled in the OASIS intervention and the control group consisted of NHs in Massachusetts and New York. The Centers for Medicare & Medicaid Services Minimum Data Set (MDS) 3.0 data was analyzed to determine medication use and behavior of residents of NHs. Residents of these NHs were excluded if they had a US Food and Drug Administration (FDA)-approved indication for antipsychotic use (eg, schizophrenia); were short-term residents (length of stay < 90 days); or had missing data on psychopharmacological medication use or behavior.

Intervention. The OASIS is an educational program that targeted both direct care and non-direct care staff in NHs to assist them in meeting the needs and challenges of caring for long-term care residents. Utilizing a train-the-trainer model, OASIS program coordinators and champions from each intervention NH participated in an 8-hour in-person training session that focused on enhancing communication skills between NH staff and residents with cognitive impairment. These trainers subsequently instructed the OASIS program to staff at their respective NHs using a team-based care approach. Addi-tional support of the OASIS educational program, such as telephone support, 12 webinars, 2 regional seminars, and 2 booster sessions, were provided to participating NHs.

Main outcome measures. The main outcome measure was facility-level prevalence of antipsychotic use in long-term NH residents captured by MDS in the 7 days preceding the MDS assessment. The secondary outcome measures were facility-level quarterly prevalence of psychotropic medications that may have been substituted for antipsychotic medications (ie, anxiolytics, antidepressants, and hypnotics) and behavioral disturbances (ie, physically abusive behavior, verbally abusive behavior, and rejecting care). All secondary outcomes were dichotomized in the 7 days preceding the MDS assessment and aggregated at the facility level for each quarter.

The analysis utilized an interrupted time series model of facility-level prevalence of antipsychotic medication use, other psychotropic medication use, and behavioral disturbances to evaluate the OASIS intervention’s effectiveness in participating facilities compared with control NHs. This methodology allowed the assessment of changes in the trend of antipsychotic use after the OASIS intervention controlling for historical trends. Data from the 18-month pre-intervention (baseline) period was compared with that of a 3-month training phase, a 6-month implementation phase, and a 3-month maintenance phase.

Main results. 93 NHs received OASIS intervention (27 with high prevalence of antipsychotic use) while 831 NHs did not (non-intervention control). The intervention NHs had a higher prevalence of antipsychotic use before OASIS training (baseline period) than the control NHs (34.1% vs. 22.7%, P < 0.001). The intervention NHs compared to controls were smaller in size (122 beds [interquartile range {IQR}, 88–152 beds] vs. 140 beds; [IQR, 104–200 beds]; P < 0.001), more likely to be for profit (77.4% vs. 62.0%, P = 0.009), had corporate ownership (93.5% vs. 74.6%, P < 0.001), and provided resident-only councils (78.5% vs. 52.9%, P < 0.001). The intervention NHs had higher registered nurse (RN) staffing hours per resident (0.8 vs. 0.7; P = 0.01) but lower certified nursing assistant (CNA) hours per resident (2.3 vs. 2.4; P = 0.04) than control NHs. There was no difference in licensed practical nurse hours per resident between groups.

All 93 intervention NHs completed the 8-hour in-person training session and attended an average of 6.5 (range, 0–12) subsequent support webinars. Thirteen NHs (14.0%) attended no regional seminars, 32 (34.4%) attended one, and 48 (51.6%) attended both. Four NHs (4.3%) attended one booster session, and 13 (14.0%) attended both. The NH staff most often trained in the OASIS training program were the directors of nursing, RNs, CNAs, and activities personnel. Support staff including housekeeping and dietary were trained in about half of the reporting intervention NHs, while physicians and nurse practitioners participated infrequently. Concurrent training programs in dementia care (Hand-in-Hand, Alzheimer Association training, MassPRO dementia care training) were implemented in 67.2% of intervention NHs.

In the intervention NHs, the prevalence of antipsych-otic prescribing decreased from 34.1% at baseline to 26.5% at the study end (7.6% absolute reduction, 22.3% relative reduction). In comparison, the prevalence of antipsychotic prescribing in control NHs decreased from 22.7% to 18.8% over the same period (3.9% absolute reduction, 17.2% relative reduction). During the OASIS implementation phase, the intervention NHs had a reduc-tion in prevalence of antipsychotic use (–1.20% [95% confidence interval {CI}, –1.85% to –0.09% per quarter]) greater than that of the control NHs (–0.23% [95% CI, –0.47% to 0.01% per quarter]), resulting in a net OASIS influence of –0.97% (95% CI, –1.85% to –0.09% per quarter; P = 0.03). The antipsychotic use reduction observed in the implementation phase was not sustained in the maintenance phase (difference of 0.93%; 95% CI, –0.66% to 2.54%; P = 0.48). No increases in other psychotropic medication use (anxiolytics, antidepressants, hypnotics) or behavioral disturbances (physically abusive behavior, verbally abusive behavior, and rejecting care) were observed during the OASIS training and implementation phases.

Conclusion. The OASIS communication training program reduced the prevalence of antipsychotic use in NHs during its implementation phase, but its effect was not sustained in the subsequent maintenance phase. The use of other psychotropic medications and behavior disturbances did not increase during the implementation of OASIS program. The findings from this study provided further support for utilizing nonpharmacologic programs to treat behavioral and psychological symptoms of dementia in older adults who reside in NHs.

Commentary

The use of both conventional and atypical antipsychotic medications is associated with a dose-related, approximately 2-fold increased risk of sudden cardiac death in older adults [1,2]. In 2006, the FDA issued a public health advisory stating that both conventional and atypical anti-psychotic medications are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. Despite this black box warning and growing recognition that antipsychotic medications are not indicated for the treatment of dementia-related psychosis, the off-label use of antipsychotic medications to treat behavioral and psychological symptoms of dementia in older adults remains a common practice in nursing homes [3]. Thus, there is an urgent need to assess and develop effective interventions that reduce the practice of antipsychotic medication prescribing in long-term care. To that effect, the study reported by Tjia et al appropriately investigated the impact of the OASIS communication training program, a nonpharmacologic intervention, on the reduction of antipsychotic use in NHs.

This study was well designed and had a number of strengths. It utilized an interrupted time series model, one of the strongest quasi-experimental approaches due to its robustness to threats of internal validity, for evaluating longitudinal effects of an intervention intended to improve the quality of medication use. Moreover, this study included a large sample size and comparison facilities from the same geographical areas (NHs in Massachusetts and New York State) that served as external controls. Several potential weaknesses of the study were identified. Because facility-level aggregate data from NHs were used for analysis, individual level (long-term care resident) characteristics were not accounted for in the analysis. In addition, while the post-OASIS intervention questionnaire response rate was 65.6% (61 of 93 intervention NHs), a higher response rate would provide better characterization of NH staff that participated in OASIS program training, program completion rate, and a more complete representation of competing dementia care training programs concurrently implemented in these NHs.

Several studies, most utilizing various provider education methods, had explored whether these interventions could curb antipsychotic use in NHs with limited success. The largest successful intervention was reported by Meador et al [4], where a focused provider education program facilitated a relative reduction in antipsychotic medication use of 23% compared to control NHs. However, the implementation of this specific program was time- and resource-intensive, requiring geropsychiatry evaluation to all physicians (45 to 60 min), nurse-educator in-service programs for NH staff (5 to 6 one-hr sessions), management specialist consultation to NH administrators (4 hr), and evening meeting for the families of NH residents. The current study by Tjia et al, the largest study to date conducted in the context of competing dementia care training programs and increased awareness of the danger of antipsychotic use in the elderly, similarly showed a meaningful reduction in antipsychotic medication use in NHs that received the OASIS communication training program. The OASIS program appears to be less resource-intensive than the provider education program modeled by Meador et al, and its train-the-trainer model is likely more adaptable to meet the limitations (eg, low staffing and staff turnover) inherent in NHs. The beneficial effect of the OASIS program on reduction of antipsychotic medication prescribing was observed despite low participation by prescribers (11.5% of physicians and 11.5% of nurse practitioners). Although it is unclear why this was observed, this finding is intriguing in that a communication training program that reframes challenging behavior of NH residents with cognitive impairment as (1) communication of unmet needs, (2) train staff to anticipate resident needs, and (3) integrate resident strengths into daily care plans can alter provider prescription behavior. The implication of this is that provider practice in managing behavioral and psychological symptoms of dementia can be improved by optimizing communication training in NH staff. Taken together, this study adds to evidence in favor of utilizing nonpharmacologic interventions to reduce antipsychotic use in long-term care.

Applications for Clinical Practice

OASIS, a communication training program for NH staff, reduces antipsychotic medication use in NHs during its implementation phase. Future studies need to investigate pragmatic methods to sustain the beneficial effect of OASIS after its implementation phase.

—Fred Ko, MD, MS, Icahn School of Medicine at Mount Sinai, New York, NY

Study Overview

Objective. To evaluate the effectiveness of OASIS, a large-scale, statewide communication training program, on the reduction of antipsychotic use in nursing homes (NHs).

Design. Quasi-experimental longitudinal study with external controls.

Setting and participants. The participants were residents living in NHs between 1 March 2011 and 31 August 2013. The intervention group consisted of NHs in Massachusetts that were enrolled in the OASIS intervention and the control group consisted of NHs in Massachusetts and New York. The Centers for Medicare & Medicaid Services Minimum Data Set (MDS) 3.0 data was analyzed to determine medication use and behavior of residents of NHs. Residents of these NHs were excluded if they had a US Food and Drug Administration (FDA)-approved indication for antipsychotic use (eg, schizophrenia); were short-term residents (length of stay < 90 days); or had missing data on psychopharmacological medication use or behavior.

Intervention. The OASIS is an educational program that targeted both direct care and non-direct care staff in NHs to assist them in meeting the needs and challenges of caring for long-term care residents. Utilizing a train-the-trainer model, OASIS program coordinators and champions from each intervention NH participated in an 8-hour in-person training session that focused on enhancing communication skills between NH staff and residents with cognitive impairment. These trainers subsequently instructed the OASIS program to staff at their respective NHs using a team-based care approach. Addi-tional support of the OASIS educational program, such as telephone support, 12 webinars, 2 regional seminars, and 2 booster sessions, were provided to participating NHs.

Main outcome measures. The main outcome measure was facility-level prevalence of antipsychotic use in long-term NH residents captured by MDS in the 7 days preceding the MDS assessment. The secondary outcome measures were facility-level quarterly prevalence of psychotropic medications that may have been substituted for antipsychotic medications (ie, anxiolytics, antidepressants, and hypnotics) and behavioral disturbances (ie, physically abusive behavior, verbally abusive behavior, and rejecting care). All secondary outcomes were dichotomized in the 7 days preceding the MDS assessment and aggregated at the facility level for each quarter.

The analysis utilized an interrupted time series model of facility-level prevalence of antipsychotic medication use, other psychotropic medication use, and behavioral disturbances to evaluate the OASIS intervention’s effectiveness in participating facilities compared with control NHs. This methodology allowed the assessment of changes in the trend of antipsychotic use after the OASIS intervention controlling for historical trends. Data from the 18-month pre-intervention (baseline) period was compared with that of a 3-month training phase, a 6-month implementation phase, and a 3-month maintenance phase.

Main results. 93 NHs received OASIS intervention (27 with high prevalence of antipsychotic use) while 831 NHs did not (non-intervention control). The intervention NHs had a higher prevalence of antipsychotic use before OASIS training (baseline period) than the control NHs (34.1% vs. 22.7%, P < 0.001). The intervention NHs compared to controls were smaller in size (122 beds [interquartile range {IQR}, 88–152 beds] vs. 140 beds; [IQR, 104–200 beds]; P < 0.001), more likely to be for profit (77.4% vs. 62.0%, P = 0.009), had corporate ownership (93.5% vs. 74.6%, P < 0.001), and provided resident-only councils (78.5% vs. 52.9%, P < 0.001). The intervention NHs had higher registered nurse (RN) staffing hours per resident (0.8 vs. 0.7; P = 0.01) but lower certified nursing assistant (CNA) hours per resident (2.3 vs. 2.4; P = 0.04) than control NHs. There was no difference in licensed practical nurse hours per resident between groups.

All 93 intervention NHs completed the 8-hour in-person training session and attended an average of 6.5 (range, 0–12) subsequent support webinars. Thirteen NHs (14.0%) attended no regional seminars, 32 (34.4%) attended one, and 48 (51.6%) attended both. Four NHs (4.3%) attended one booster session, and 13 (14.0%) attended both. The NH staff most often trained in the OASIS training program were the directors of nursing, RNs, CNAs, and activities personnel. Support staff including housekeeping and dietary were trained in about half of the reporting intervention NHs, while physicians and nurse practitioners participated infrequently. Concurrent training programs in dementia care (Hand-in-Hand, Alzheimer Association training, MassPRO dementia care training) were implemented in 67.2% of intervention NHs.

In the intervention NHs, the prevalence of antipsych-otic prescribing decreased from 34.1% at baseline to 26.5% at the study end (7.6% absolute reduction, 22.3% relative reduction). In comparison, the prevalence of antipsychotic prescribing in control NHs decreased from 22.7% to 18.8% over the same period (3.9% absolute reduction, 17.2% relative reduction). During the OASIS implementation phase, the intervention NHs had a reduc-tion in prevalence of antipsychotic use (–1.20% [95% confidence interval {CI}, –1.85% to –0.09% per quarter]) greater than that of the control NHs (–0.23% [95% CI, –0.47% to 0.01% per quarter]), resulting in a net OASIS influence of –0.97% (95% CI, –1.85% to –0.09% per quarter; P = 0.03). The antipsychotic use reduction observed in the implementation phase was not sustained in the maintenance phase (difference of 0.93%; 95% CI, –0.66% to 2.54%; P = 0.48). No increases in other psychotropic medication use (anxiolytics, antidepressants, hypnotics) or behavioral disturbances (physically abusive behavior, verbally abusive behavior, and rejecting care) were observed during the OASIS training and implementation phases.

Conclusion. The OASIS communication training program reduced the prevalence of antipsychotic use in NHs during its implementation phase, but its effect was not sustained in the subsequent maintenance phase. The use of other psychotropic medications and behavior disturbances did not increase during the implementation of OASIS program. The findings from this study provided further support for utilizing nonpharmacologic programs to treat behavioral and psychological symptoms of dementia in older adults who reside in NHs.

Commentary

The use of both conventional and atypical antipsychotic medications is associated with a dose-related, approximately 2-fold increased risk of sudden cardiac death in older adults [1,2]. In 2006, the FDA issued a public health advisory stating that both conventional and atypical anti-psychotic medications are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. Despite this black box warning and growing recognition that antipsychotic medications are not indicated for the treatment of dementia-related psychosis, the off-label use of antipsychotic medications to treat behavioral and psychological symptoms of dementia in older adults remains a common practice in nursing homes [3]. Thus, there is an urgent need to assess and develop effective interventions that reduce the practice of antipsychotic medication prescribing in long-term care. To that effect, the study reported by Tjia et al appropriately investigated the impact of the OASIS communication training program, a nonpharmacologic intervention, on the reduction of antipsychotic use in NHs.

This study was well designed and had a number of strengths. It utilized an interrupted time series model, one of the strongest quasi-experimental approaches due to its robustness to threats of internal validity, for evaluating longitudinal effects of an intervention intended to improve the quality of medication use. Moreover, this study included a large sample size and comparison facilities from the same geographical areas (NHs in Massachusetts and New York State) that served as external controls. Several potential weaknesses of the study were identified. Because facility-level aggregate data from NHs were used for analysis, individual level (long-term care resident) characteristics were not accounted for in the analysis. In addition, while the post-OASIS intervention questionnaire response rate was 65.6% (61 of 93 intervention NHs), a higher response rate would provide better characterization of NH staff that participated in OASIS program training, program completion rate, and a more complete representation of competing dementia care training programs concurrently implemented in these NHs.

Several studies, most utilizing various provider education methods, had explored whether these interventions could curb antipsychotic use in NHs with limited success. The largest successful intervention was reported by Meador et al [4], where a focused provider education program facilitated a relative reduction in antipsychotic medication use of 23% compared to control NHs. However, the implementation of this specific program was time- and resource-intensive, requiring geropsychiatry evaluation to all physicians (45 to 60 min), nurse-educator in-service programs for NH staff (5 to 6 one-hr sessions), management specialist consultation to NH administrators (4 hr), and evening meeting for the families of NH residents. The current study by Tjia et al, the largest study to date conducted in the context of competing dementia care training programs and increased awareness of the danger of antipsychotic use in the elderly, similarly showed a meaningful reduction in antipsychotic medication use in NHs that received the OASIS communication training program. The OASIS program appears to be less resource-intensive than the provider education program modeled by Meador et al, and its train-the-trainer model is likely more adaptable to meet the limitations (eg, low staffing and staff turnover) inherent in NHs. The beneficial effect of the OASIS program on reduction of antipsychotic medication prescribing was observed despite low participation by prescribers (11.5% of physicians and 11.5% of nurse practitioners). Although it is unclear why this was observed, this finding is intriguing in that a communication training program that reframes challenging behavior of NH residents with cognitive impairment as (1) communication of unmet needs, (2) train staff to anticipate resident needs, and (3) integrate resident strengths into daily care plans can alter provider prescription behavior. The implication of this is that provider practice in managing behavioral and psychological symptoms of dementia can be improved by optimizing communication training in NH staff. Taken together, this study adds to evidence in favor of utilizing nonpharmacologic interventions to reduce antipsychotic use in long-term care.

Applications for Clinical Practice

OASIS, a communication training program for NH staff, reduces antipsychotic medication use in NHs during its implementation phase. Future studies need to investigate pragmatic methods to sustain the beneficial effect of OASIS after its implementation phase.

—Fred Ko, MD, MS, Icahn School of Medicine at Mount Sinai, New York, NY

Study Overview

Objective. To evaluate long-term adherence to antihypertensive therapy among patients on fixed-dose combination medication as well as antihypertensive monotherapy; and to identify demographic and clinical risk factors associated with selection of and adherence and persistence to antihypertensive medication therapy.

Design. Retrospective cohort study using claims data from a large nationwide insurer.

Setting and participants. The study population included patients older than age 18 who initiated antihypertensive medication between 1 January 2009 and 31 December 2012 and who were continually enrolled at least 180 days before and 365 days after the index date, defined as the date of initiation of antihypertensive therapy. Patients were excluded from the study if they had previously filled any antihypertensive medication at any time prior to the index date. Patients were categorized based on the number and type of antihypertensive medications (fixed-dose combination, defined as a single pill containing multiple medications; multi-pill combination, defined as 2 or more distinct antihypertensive tablets or capsules; or single therapy, defined as only 1 medication) using National Drug Codes (NDC). Study authors also measured patient baseline characteristics, such as age, region, gender, diagnoses as defined by ICD-9 codes, patient utilization characteristics (both outpatient visits and hospitalizations) and characteristics of the initiated medication, including patient copayment and number of days of medication supplied.

Main outcome measures. The primary outcome of inte-rest was persistence, defined as having supply for any antihypertensive medication that overlapped with the 365th day after initiation (index date), whether the initiated medication or other antihypertensive. Additional outcomes included adherence to at least 1 antihypertensive in the 12 months after initiation and refilling at least 1 antihypertensive medication. To determine adherence, the study authors calculated the proportion of days the patient had any antihypertensive available to them (proportion of days covered; PDC). PDC > 80% to at least 1 antihypertensive in the 12 months after initiation was defined as “fully adherent.”

Statistical analysis utilized modified multivariable Poisson regression models and sensitivity analyses were performed. The main study comparisons focused on patients initiating fixed-dose combination therapy and monotherapy because these groups were more comparable in terms of baseline characteristics and medications initiated than the multi-pill combination group.

Main results. The study sample consisted of 484,493 patients who initiated an oral antihypertensive, including 78,958 patient initiating fixed-dose combinations, 380,269 filled a single therapy, and 22,266 who initiated multi-pill combinations. The most frequently initiated fixed-dose combination was lisinopril-hydrochlorothiazide. Lisinopril, hydrochlorothiazide, and amlodipine with the most frequently initiated monotherapy. The mean age of the study population was 47.2 years and 51.8% were women. Patients initiating multiple pill combinations were older (mean age 52.5) and tended to be sicker with more comorbidities than fixed-dose combinations or monotherapy. Patients initiating fixed-dose combination had higher prescription copayments than patients using single medication (prescription copay $14.4 versus $9.6). Patients initiating fixed-dose combinations were 9% more likely to be persistent (relative risk [RR] 1.09, 95% CI 1.08–1.10) and 13% more likely to be adherent (RR 1.13, 95% CI 1.11–1.14) than those who started on a monotherapy. Refill rates were also slightly higher among fixed-dose combination initiators (RR 1.06, 95% CI 1.05-1.07).

Conclusion. Compared with monotherapy, fixed-dose combination therapy appears to improve adherence and persistence to antihypertensive medications.

Commentary

Approximately half of US of individuals with diagnosed hypertension obtain control of their condition based on currently defined targets [1]. The most effective approach to blood pressure management has been controversial. The JNC8 [2] guidelines liberalized blood pressure targets, while recent results from the SPRINT (systolic blood pressure intervention trial) [3] indicates that lower blood pressure targets are able to prevent hypertension-related complications without significant additional risk. Given these conflicts, there is clearly ambiguity in the most effective approach to initiating antihypertensive treatment. Prior studies have shown that fewer than 50% of patients continue to take their medications just 12 months after initiation [4,5].

Fixed-dose combination therapy for blood pressure management has been cited as better for adherence and is now making its way into clinical guidelines [6–8]. However, it should be noted that fixed-dose combination therapy for blood pressure management limits dosing flexibility. Dose titration may be needed, potentially leading to additional prescriptions, thus potentially complicating the drug regimen and adding additional cost. Complicating matters further, quality metrics and reporting requirements for hypertension require primary care providers to achieve blood pressure control while also ensuring patient adherence and concomitantly avoiding side effects related to medication therapy.

This study was conducted using claims data for commercially insured patients or those with Medicare Advan-tage and is unlikely to be representative of the entire population. Additionally, the study authors did not have detailed clinical information about patients, limiting the ability to understand the true clinical implications. Further, patients may have initiated medications for indications other than hypertension. In addition, causality cannot be established given the retrospective observational cohort nature of this study.

Applications for Clinical Practice

Primary care physicians face substantial challenges in the treatment of hypertension, including with respect to selection of initial medication therapy. Results from this study add to the evidence base that fixed-dose combination therapy is more effective in obtaining blood pressure control than monotherapy or multiple-pill therapy. Medication adherence in primary care practice is challenging. Strategies such as fixed-dose combination therapy are reasonable to employ to improve medication adherence; however, costs must be considered.

—Ajay Dharod, MD, Wake Forest School of Medicine, Winston-Salem, NC

Study Overview

Objective. To evaluate long-term adherence to antihypertensive therapy among patients on fixed-dose combination medication as well as antihypertensive monotherapy; and to identify demographic and clinical risk factors associated with selection of and adherence and persistence to antihypertensive medication therapy.

Design. Retrospective cohort study using claims data from a large nationwide insurer.

Setting and participants. The study population included patients older than age 18 who initiated antihypertensive medication between 1 January 2009 and 31 December 2012 and who were continually enrolled at least 180 days before and 365 days after the index date, defined as the date of initiation of antihypertensive therapy. Patients were excluded from the study if they had previously filled any antihypertensive medication at any time prior to the index date. Patients were categorized based on the number and type of antihypertensive medications (fixed-dose combination, defined as a single pill containing multiple medications; multi-pill combination, defined as 2 or more distinct antihypertensive tablets or capsules; or single therapy, defined as only 1 medication) using National Drug Codes (NDC). Study authors also measured patient baseline characteristics, such as age, region, gender, diagnoses as defined by ICD-9 codes, patient utilization characteristics (both outpatient visits and hospitalizations) and characteristics of the initiated medication, including patient copayment and number of days of medication supplied.

Main outcome measures. The primary outcome of inte-rest was persistence, defined as having supply for any antihypertensive medication that overlapped with the 365th day after initiation (index date), whether the initiated medication or other antihypertensive. Additional outcomes included adherence to at least 1 antihypertensive in the 12 months after initiation and refilling at least 1 antihypertensive medication. To determine adherence, the study authors calculated the proportion of days the patient had any antihypertensive available to them (proportion of days covered; PDC). PDC > 80% to at least 1 antihypertensive in the 12 months after initiation was defined as “fully adherent.”

Statistical analysis utilized modified multivariable Poisson regression models and sensitivity analyses were performed. The main study comparisons focused on patients initiating fixed-dose combination therapy and monotherapy because these groups were more comparable in terms of baseline characteristics and medications initiated than the multi-pill combination group.

Main results. The study sample consisted of 484,493 patients who initiated an oral antihypertensive, including 78,958 patient initiating fixed-dose combinations, 380,269 filled a single therapy, and 22,266 who initiated multi-pill combinations. The most frequently initiated fixed-dose combination was lisinopril-hydrochlorothiazide. Lisinopril, hydrochlorothiazide, and amlodipine with the most frequently initiated monotherapy. The mean age of the study population was 47.2 years and 51.8% were women. Patients initiating multiple pill combinations were older (mean age 52.5) and tended to be sicker with more comorbidities than fixed-dose combinations or monotherapy. Patients initiating fixed-dose combination had higher prescription copayments than patients using single medication (prescription copay $14.4 versus $9.6). Patients initiating fixed-dose combinations were 9% more likely to be persistent (relative risk [RR] 1.09, 95% CI 1.08–1.10) and 13% more likely to be adherent (RR 1.13, 95% CI 1.11–1.14) than those who started on a monotherapy. Refill rates were also slightly higher among fixed-dose combination initiators (RR 1.06, 95% CI 1.05-1.07).

Conclusion. Compared with monotherapy, fixed-dose combination therapy appears to improve adherence and persistence to antihypertensive medications.

Commentary

Approximately half of US of individuals with diagnosed hypertension obtain control of their condition based on currently defined targets [1]. The most effective approach to blood pressure management has been controversial. The JNC8 [2] guidelines liberalized blood pressure targets, while recent results from the SPRINT (systolic blood pressure intervention trial) [3] indicates that lower blood pressure targets are able to prevent hypertension-related complications without significant additional risk. Given these conflicts, there is clearly ambiguity in the most effective approach to initiating antihypertensive treatment. Prior studies have shown that fewer than 50% of patients continue to take their medications just 12 months after initiation [4,5].

Fixed-dose combination therapy for blood pressure management has been cited as better for adherence and is now making its way into clinical guidelines [6–8]. However, it should be noted that fixed-dose combination therapy for blood pressure management limits dosing flexibility. Dose titration may be needed, potentially leading to additional prescriptions, thus potentially complicating the drug regimen and adding additional cost. Complicating matters further, quality metrics and reporting requirements for hypertension require primary care providers to achieve blood pressure control while also ensuring patient adherence and concomitantly avoiding side effects related to medication therapy.

This study was conducted using claims data for commercially insured patients or those with Medicare Advan-tage and is unlikely to be representative of the entire population. Additionally, the study authors did not have detailed clinical information about patients, limiting the ability to understand the true clinical implications. Further, patients may have initiated medications for indications other than hypertension. In addition, causality cannot be established given the retrospective observational cohort nature of this study.

Applications for Clinical Practice

Primary care physicians face substantial challenges in the treatment of hypertension, including with respect to selection of initial medication therapy. Results from this study add to the evidence base that fixed-dose combination therapy is more effective in obtaining blood pressure control than monotherapy or multiple-pill therapy. Medication adherence in primary care practice is challenging. Strategies such as fixed-dose combination therapy are reasonable to employ to improve medication adherence; however, costs must be considered.

—Ajay Dharod, MD, Wake Forest School of Medicine, Winston-Salem, NC

Study Overview

Objective. To evaluate long-term adherence to antihypertensive therapy among patients on fixed-dose combination medication as well as antihypertensive monotherapy; and to identify demographic and clinical risk factors associated with selection of and adherence and persistence to antihypertensive medication therapy.

Design. Retrospective cohort study using claims data from a large nationwide insurer.

Setting and participants. The study population included patients older than age 18 who initiated antihypertensive medication between 1 January 2009 and 31 December 2012 and who were continually enrolled at least 180 days before and 365 days after the index date, defined as the date of initiation of antihypertensive therapy. Patients were excluded from the study if they had previously filled any antihypertensive medication at any time prior to the index date. Patients were categorized based on the number and type of antihypertensive medications (fixed-dose combination, defined as a single pill containing multiple medications; multi-pill combination, defined as 2 or more distinct antihypertensive tablets or capsules; or single therapy, defined as only 1 medication) using National Drug Codes (NDC). Study authors also measured patient baseline characteristics, such as age, region, gender, diagnoses as defined by ICD-9 codes, patient utilization characteristics (both outpatient visits and hospitalizations) and characteristics of the initiated medication, including patient copayment and number of days of medication supplied.

Main outcome measures. The primary outcome of inte-rest was persistence, defined as having supply for any antihypertensive medication that overlapped with the 365th day after initiation (index date), whether the initiated medication or other antihypertensive. Additional outcomes included adherence to at least 1 antihypertensive in the 12 months after initiation and refilling at least 1 antihypertensive medication. To determine adherence, the study authors calculated the proportion of days the patient had any antihypertensive available to them (proportion of days covered; PDC). PDC > 80% to at least 1 antihypertensive in the 12 months after initiation was defined as “fully adherent.”

Statistical analysis utilized modified multivariable Poisson regression models and sensitivity analyses were performed. The main study comparisons focused on patients initiating fixed-dose combination therapy and monotherapy because these groups were more comparable in terms of baseline characteristics and medications initiated than the multi-pill combination group.

Main results. The study sample consisted of 484,493 patients who initiated an oral antihypertensive, including 78,958 patient initiating fixed-dose combinations, 380,269 filled a single therapy, and 22,266 who initiated multi-pill combinations. The most frequently initiated fixed-dose combination was lisinopril-hydrochlorothiazide. Lisinopril, hydrochlorothiazide, and amlodipine with the most frequently initiated monotherapy. The mean age of the study population was 47.2 years and 51.8% were women. Patients initiating multiple pill combinations were older (mean age 52.5) and tended to be sicker with more comorbidities than fixed-dose combinations or monotherapy. Patients initiating fixed-dose combination had higher prescription copayments than patients using single medication (prescription copay $14.4 versus $9.6). Patients initiating fixed-dose combinations were 9% more likely to be persistent (relative risk [RR] 1.09, 95% CI 1.08–1.10) and 13% more likely to be adherent (RR 1.13, 95% CI 1.11–1.14) than those who started on a monotherapy. Refill rates were also slightly higher among fixed-dose combination initiators (RR 1.06, 95% CI 1.05-1.07).

Conclusion. Compared with monotherapy, fixed-dose combination therapy appears to improve adherence and persistence to antihypertensive medications.

Commentary

Approximately half of US of individuals with diagnosed hypertension obtain control of their condition based on currently defined targets [1]. The most effective approach to blood pressure management has been controversial. The JNC8 [2] guidelines liberalized blood pressure targets, while recent results from the SPRINT (systolic blood pressure intervention trial) [3] indicates that lower blood pressure targets are able to prevent hypertension-related complications without significant additional risk. Given these conflicts, there is clearly ambiguity in the most effective approach to initiating antihypertensive treatment. Prior studies have shown that fewer than 50% of patients continue to take their medications just 12 months after initiation [4,5].

Fixed-dose combination therapy for blood pressure management has been cited as better for adherence and is now making its way into clinical guidelines [6–8]. However, it should be noted that fixed-dose combination therapy for blood pressure management limits dosing flexibility. Dose titration may be needed, potentially leading to additional prescriptions, thus potentially complicating the drug regimen and adding additional cost. Complicating matters further, quality metrics and reporting requirements for hypertension require primary care providers to achieve blood pressure control while also ensuring patient adherence and concomitantly avoiding side effects related to medication therapy.

This study was conducted using claims data for commercially insured patients or those with Medicare Advan-tage and is unlikely to be representative of the entire population. Additionally, the study authors did not have detailed clinical information about patients, limiting the ability to understand the true clinical implications. Further, patients may have initiated medications for indications other than hypertension. In addition, causality cannot be established given the retrospective observational cohort nature of this study.

Applications for Clinical Practice

Primary care physicians face substantial challenges in the treatment of hypertension, including with respect to selection of initial medication therapy. Results from this study add to the evidence base that fixed-dose combination therapy is more effective in obtaining blood pressure control than monotherapy or multiple-pill therapy. Medication adherence in primary care practice is challenging. Strategies such as fixed-dose combination therapy are reasonable to employ to improve medication adherence; however, costs must be considered.

—Ajay Dharod, MD, Wake Forest School of Medicine, Winston-Salem, NC

Unless you have been assigned to the post or the hospital, you have probably never heard of Leonard Wood. Leonard Wood arguably had the most distinguished military-government career of someone who did not become president. Wood was a Harvard-educated physician, pursued the Apache Chief Geronimo, received the Medal of Honor, was physician to 2 U.S. presidents, served as U.S. army chief of staff, was a successful military governor, ran for president, was a colleague of Walter Reed, and was commander-inarms for President Theodore Roosevelt.

Wood was born in 1860 to an established New England family; his father was a Union Army physician during the Civil War and was practicing on Cape Cod when he died unexpectedly in 1880. The family was left destitute, but Wood was able to continue his education when a wealthy family friend agreed to pay for him to attend Harvard Medical School, which at the time did not require any prior college. He graduated in 1883 and was selected for a prized internship at Boston City Hospital; however, he was dismissed for a rule violation that the program director later admitted was a mistake.

Unable to support himself in practice in Boston, Wood turned to the U.S. Army, a decision that would change his life. Assigned to Fort Huachuca in Arizona, Wood participated in the yearlong pursuit and final surrender of Geronimo; for his role he was awarded the Medal of Honor in 1898. His experiences in the wild and rugged terrain of the west triggered a legendary and lifelong pursuit of hard and stressful physical activity. Transferred to California, Wood met Louise Condit-Smith, ward of an associate justice of the U.S. Supreme Court. When they married in November 1890 in Washington, DC, the ceremony was attended by all of the Supreme Court justices.

In 1893 while assigned to Fort McPherson outside Atlanta, Wood, whose duties were not demanding, needed a physical outlet for his unbounded energies. He enrolled at Georgia Tech at age 33 to play football. He was eligible to play because he had not previously attended college. He scored 5 touchdowns, winning the game against rival University of Georgia.

Later, Wood was assigned to Washington, where he quickly became known and sought after as a physician. He served many of the political and military elite, including presidents Grover Cleveland and William McKinley. In 1897, he met Theodore Roosevelt, the 38-year-old assistant secretary of the U.S. Navy who shared his love of outdoor adventure and the military. They became fast friends/companions/competitors; Roosevelt wrote to a friend that he had found a “playmate.”

When the U.S.S. Maine was sunk in Havana Harbor in 1898 and war was declared on Spain, Wood and Roosevelt schemed on how to go to war together. Wood the career soldier and Roosevelt the career politician had excellent connections and became commander and deputy commander of the First Volunteer Calvary, later famously known as the Rough Riders. When a more senior general became ill, Wood was promoted to brigadier general, and Roosevelt became the regiment colonel.

After the war, Wood became military governor of Cuba and major general of volunteers. During the U.S. occupation, Walter Reed was sent to investigate infectious diseases, including yellow fever. Wood provided $10,000 to fund the second phase of Reed’s research and approved the use of human volunteers. When the U.S. occupation ended in 1902, Wood was to revert to captain, medical corps.

Wood’s success in Cuba was obvious and wel l known; President McKinley promoted him to U.S. Army brigadier general. At that time, as a brigadier general, Wood was essentially guaranteed a second star and a rotation through the chief of staff position. He served as chief of staff from 1910 to 1914, the only physician ever to do so. As chief of staff he eliminated the antiquated bureau system, developed the maneuver unit concept, and laid the groundwork for the Reserve Officers’ Training Corps.

Wood stayed on active duty and rotated through other senior-level positions. Because of Wood’s political activity promoting universal service and improving readiness, President Woodrow Wilson passed over him, instead selecting John J. Pershing to command the American Expeditionary Force in World War I. Wood stayed politically active and ran for the Republican presidential nomination in 1920, losing to Warren G. Harding at the convention. Wood was appointed governor general of the Philippines, a position he held until his death in 1927.

While in Cuba, Wood was severely injured by striking his head on a chandelier, most likely resulting in an undiagnosed skull fracture. Over time he developed neurologic symptoms and was seen by neurosurgeon Harvey Cushing, MD, at Johns Hopkins, who removed a meningioma in February 1910. Wood made a dramatic recovery. Over a decade later while in the Philippines, his symptoms returned, and after significant delay he went home to see Cushing who was then at Harvard Medical School. When Wood died after surgery, Cushing admitted that he should not have tackled such a difficult case so quickly after returning from a trip to Europe.

Fort Leonard Wood in Missouri and the on-base General Leonard Wood U.S. Army Community Hospital are named in Wood’s honor.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual
your facility was named for or to offer a topic suggestion, contact us at fedprac@frontlinemedcom.com or on Facebook.

Unless you have been assigned to the post or the hospital, you have probably never heard of Leonard Wood. Leonard Wood arguably had the most distinguished military-government career of someone who did not become president. Wood was a Harvard-educated physician, pursued the Apache Chief Geronimo, received the Medal of Honor, was physician to 2 U.S. presidents, served as U.S. army chief of staff, was a successful military governor, ran for president, was a colleague of Walter Reed, and was commander-inarms for President Theodore Roosevelt.

Wood was born in 1860 to an established New England family; his father was a Union Army physician during the Civil War and was practicing on Cape Cod when he died unexpectedly in 1880. The family was left destitute, but Wood was able to continue his education when a wealthy family friend agreed to pay for him to attend Harvard Medical School, which at the time did not require any prior college. He graduated in 1883 and was selected for a prized internship at Boston City Hospital; however, he was dismissed for a rule violation that the program director later admitted was a mistake.

Unable to support himself in practice in Boston, Wood turned to the U.S. Army, a decision that would change his life. Assigned to Fort Huachuca in Arizona, Wood participated in the yearlong pursuit and final surrender of Geronimo; for his role he was awarded the Medal of Honor in 1898. His experiences in the wild and rugged terrain of the west triggered a legendary and lifelong pursuit of hard and stressful physical activity. Transferred to California, Wood met Louise Condit-Smith, ward of an associate justice of the U.S. Supreme Court. When they married in November 1890 in Washington, DC, the ceremony was attended by all of the Supreme Court justices.

In 1893 while assigned to Fort McPherson outside Atlanta, Wood, whose duties were not demanding, needed a physical outlet for his unbounded energies. He enrolled at Georgia Tech at age 33 to play football. He was eligible to play because he had not previously attended college. He scored 5 touchdowns, winning the game against rival University of Georgia.

Later, Wood was assigned to Washington, where he quickly became known and sought after as a physician. He served many of the political and military elite, including presidents Grover Cleveland and William McKinley. In 1897, he met Theodore Roosevelt, the 38-year-old assistant secretary of the U.S. Navy who shared his love of outdoor adventure and the military. They became fast friends/companions/competitors; Roosevelt wrote to a friend that he had found a “playmate.”

When the U.S.S. Maine was sunk in Havana Harbor in 1898 and war was declared on Spain, Wood and Roosevelt schemed on how to go to war together. Wood the career soldier and Roosevelt the career politician had excellent connections and became commander and deputy commander of the First Volunteer Calvary, later famously known as the Rough Riders. When a more senior general became ill, Wood was promoted to brigadier general, and Roosevelt became the regiment colonel.

After the war, Wood became military governor of Cuba and major general of volunteers. During the U.S. occupation, Walter Reed was sent to investigate infectious diseases, including yellow fever. Wood provided $10,000 to fund the second phase of Reed’s research and approved the use of human volunteers. When the U.S. occupation ended in 1902, Wood was to revert to captain, medical corps.

Wood’s success in Cuba was obvious and wel l known; President McKinley promoted him to U.S. Army brigadier general. At that time, as a brigadier general, Wood was essentially guaranteed a second star and a rotation through the chief of staff position. He served as chief of staff from 1910 to 1914, the only physician ever to do so. As chief of staff he eliminated the antiquated bureau system, developed the maneuver unit concept, and laid the groundwork for the Reserve Officers’ Training Corps.

Wood stayed on active duty and rotated through other senior-level positions. Because of Wood’s political activity promoting universal service and improving readiness, President Woodrow Wilson passed over him, instead selecting John J. Pershing to command the American Expeditionary Force in World War I. Wood stayed politically active and ran for the Republican presidential nomination in 1920, losing to Warren G. Harding at the convention. Wood was appointed governor general of the Philippines, a position he held until his death in 1927.

While in Cuba, Wood was severely injured by striking his head on a chandelier, most likely resulting in an undiagnosed skull fracture. Over time he developed neurologic symptoms and was seen by neurosurgeon Harvey Cushing, MD, at Johns Hopkins, who removed a meningioma in February 1910. Wood made a dramatic recovery. Over a decade later while in the Philippines, his symptoms returned, and after significant delay he went home to see Cushing who was then at Harvard Medical School. When Wood died after surgery, Cushing admitted that he should not have tackled such a difficult case so quickly after returning from a trip to Europe.

Fort Leonard Wood in Missouri and the on-base General Leonard Wood U.S. Army Community Hospital are named in Wood’s honor.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual
your facility was named for or to offer a topic suggestion, contact us at fedprac@frontlinemedcom.com or on Facebook.

Unless you have been assigned to the post or the hospital, you have probably never heard of Leonard Wood. Leonard Wood arguably had the most distinguished military-government career of someone who did not become president. Wood was a Harvard-educated physician, pursued the Apache Chief Geronimo, received the Medal of Honor, was physician to 2 U.S. presidents, served as U.S. army chief of staff, was a successful military governor, ran for president, was a colleague of Walter Reed, and was commander-inarms for President Theodore Roosevelt.

Wood was born in 1860 to an established New England family; his father was a Union Army physician during the Civil War and was practicing on Cape Cod when he died unexpectedly in 1880. The family was left destitute, but Wood was able to continue his education when a wealthy family friend agreed to pay for him to attend Harvard Medical School, which at the time did not require any prior college. He graduated in 1883 and was selected for a prized internship at Boston City Hospital; however, he was dismissed for a rule violation that the program director later admitted was a mistake.

Unable to support himself in practice in Boston, Wood turned to the U.S. Army, a decision that would change his life. Assigned to Fort Huachuca in Arizona, Wood participated in the yearlong pursuit and final surrender of Geronimo; for his role he was awarded the Medal of Honor in 1898. His experiences in the wild and rugged terrain of the west triggered a legendary and lifelong pursuit of hard and stressful physical activity. Transferred to California, Wood met Louise Condit-Smith, ward of an associate justice of the U.S. Supreme Court. When they married in November 1890 in Washington, DC, the ceremony was attended by all of the Supreme Court justices.

In 1893 while assigned to Fort McPherson outside Atlanta, Wood, whose duties were not demanding, needed a physical outlet for his unbounded energies. He enrolled at Georgia Tech at age 33 to play football. He was eligible to play because he had not previously attended college. He scored 5 touchdowns, winning the game against rival University of Georgia.

Later, Wood was assigned to Washington, where he quickly became known and sought after as a physician. He served many of the political and military elite, including presidents Grover Cleveland and William McKinley. In 1897, he met Theodore Roosevelt, the 38-year-old assistant secretary of the U.S. Navy who shared his love of outdoor adventure and the military. They became fast friends/companions/competitors; Roosevelt wrote to a friend that he had found a “playmate.”

When the U.S.S. Maine was sunk in Havana Harbor in 1898 and war was declared on Spain, Wood and Roosevelt schemed on how to go to war together. Wood the career soldier and Roosevelt the career politician had excellent connections and became commander and deputy commander of the First Volunteer Calvary, later famously known as the Rough Riders. When a more senior general became ill, Wood was promoted to brigadier general, and Roosevelt became the regiment colonel.

After the war, Wood became military governor of Cuba and major general of volunteers. During the U.S. occupation, Walter Reed was sent to investigate infectious diseases, including yellow fever. Wood provided $10,000 to fund the second phase of Reed’s research and approved the use of human volunteers. When the U.S. occupation ended in 1902, Wood was to revert to captain, medical corps.

Wood’s success in Cuba was obvious and wel l known; President McKinley promoted him to U.S. Army brigadier general. At that time, as a brigadier general, Wood was essentially guaranteed a second star and a rotation through the chief of staff position. He served as chief of staff from 1910 to 1914, the only physician ever to do so. As chief of staff he eliminated the antiquated bureau system, developed the maneuver unit concept, and laid the groundwork for the Reserve Officers’ Training Corps.

Wood stayed on active duty and rotated through other senior-level positions. Because of Wood’s political activity promoting universal service and improving readiness, President Woodrow Wilson passed over him, instead selecting John J. Pershing to command the American Expeditionary Force in World War I. Wood stayed politically active and ran for the Republican presidential nomination in 1920, losing to Warren G. Harding at the convention. Wood was appointed governor general of the Philippines, a position he held until his death in 1927.

While in Cuba, Wood was severely injured by striking his head on a chandelier, most likely resulting in an undiagnosed skull fracture. Over time he developed neurologic symptoms and was seen by neurosurgeon Harvey Cushing, MD, at Johns Hopkins, who removed a meningioma in February 1910. Wood made a dramatic recovery. Over a decade later while in the Philippines, his symptoms returned, and after significant delay he went home to see Cushing who was then at Harvard Medical School. When Wood died after surgery, Cushing admitted that he should not have tackled such a difficult case so quickly after returning from a trip to Europe.

Fort Leonard Wood in Missouri and the on-base General Leonard Wood U.S. Army Community Hospital are named in Wood’s honor.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual
your facility was named for or to offer a topic suggestion, contact us at fedprac@frontlinemedcom.com or on Facebook.