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The cost of leadership
Do you practice as a team member? How is your team defined? Is it made up solely of physicians? Does it include mid-level providers? Does it extend to mental health and social service providers in your office? Do you consider nonproviders such as receptionists as team members? Do you consider the whole office “your team”? Or, is it a smaller team with just yourself and one or two other physicians along with a mid-level provider or two?
There has been a lot written about primary care teams as a natural consequence of the medical home model. In an article in AAP News, Gonzalo J. Paz-Soldán, MD, a member of the American Academy of Pediatrics Council on Community Pediatrics and regional executive medical director, pediatrics, at Reliant Medical Group, Worcester, Mass., suggests that pediatricians should be taking on leadership roles in directing these teams. He claims that in addition to improving the “quality, value, patient experience,” our leadership also will benefit “provider and staff wellness and engagement.” In other words, taking charge will return the joy of pediatrics, and make us more resilient in the face of burnout.
It’s hard to argue with the notion that having more control improves our chances of satisfaction. Most of us who owned and ran our own small practices will tell you that when we were captains of the ship, those were our most rewarding and productive years.
However, assuming a leadership in a large multilevel team of providers and support staff is another story. As Dr. Paz-Soldán observes, most of us were not trained for leadership roles. I would add that the path to medical school does not select for those skills or interest. In addition to requiring a certain set of skill and aptitudes that we may not have, leadership demands a substantial time commitment.
Leading means attending what are often poorly conceived meetings (the topic for a future Letters from Maine), and receiving and writing emails – none of which involve actually taking care of patients. Like it or not, the ugly truth is that seeing patients is what generates our bottom lines. Time spent going to meetings and communicating with your teams members cannot be considered “billable hours.”
So here is our dilemma: Do we abandon the solo and small group practice model, sell out to large entities, lose control of our professional destiny, and spend our time grousing about it? Or
There are a few saintly and gifted physicians who have the skills, energy, and commitment to become leaders and still spend enough time seeing patients to satisfy both their emotional and financial professional needs. However, in my experience, when physicians move into leadership roles, the additional responsibilities cannibalize their commitment to patient care and the skills that made them talented physicians.
Given my aversion to meetings and my disinterest in organization on a large scale, I think if I were a college student considering a career taking care of children, I would take a hard look at becoming a nurse practitioner or physician’s assistant. I might not make as much money, nor would my parents be able to introduce me as their “son the doctor.” But I would be content spending more time doing what I enjoyed.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Do you practice as a team member? How is your team defined? Is it made up solely of physicians? Does it include mid-level providers? Does it extend to mental health and social service providers in your office? Do you consider nonproviders such as receptionists as team members? Do you consider the whole office “your team”? Or, is it a smaller team with just yourself and one or two other physicians along with a mid-level provider or two?
There has been a lot written about primary care teams as a natural consequence of the medical home model. In an article in AAP News, Gonzalo J. Paz-Soldán, MD, a member of the American Academy of Pediatrics Council on Community Pediatrics and regional executive medical director, pediatrics, at Reliant Medical Group, Worcester, Mass., suggests that pediatricians should be taking on leadership roles in directing these teams. He claims that in addition to improving the “quality, value, patient experience,” our leadership also will benefit “provider and staff wellness and engagement.” In other words, taking charge will return the joy of pediatrics, and make us more resilient in the face of burnout.
It’s hard to argue with the notion that having more control improves our chances of satisfaction. Most of us who owned and ran our own small practices will tell you that when we were captains of the ship, those were our most rewarding and productive years.
However, assuming a leadership in a large multilevel team of providers and support staff is another story. As Dr. Paz-Soldán observes, most of us were not trained for leadership roles. I would add that the path to medical school does not select for those skills or interest. In addition to requiring a certain set of skill and aptitudes that we may not have, leadership demands a substantial time commitment.
Leading means attending what are often poorly conceived meetings (the topic for a future Letters from Maine), and receiving and writing emails – none of which involve actually taking care of patients. Like it or not, the ugly truth is that seeing patients is what generates our bottom lines. Time spent going to meetings and communicating with your teams members cannot be considered “billable hours.”
So here is our dilemma: Do we abandon the solo and small group practice model, sell out to large entities, lose control of our professional destiny, and spend our time grousing about it? Or
There are a few saintly and gifted physicians who have the skills, energy, and commitment to become leaders and still spend enough time seeing patients to satisfy both their emotional and financial professional needs. However, in my experience, when physicians move into leadership roles, the additional responsibilities cannibalize their commitment to patient care and the skills that made them talented physicians.
Given my aversion to meetings and my disinterest in organization on a large scale, I think if I were a college student considering a career taking care of children, I would take a hard look at becoming a nurse practitioner or physician’s assistant. I might not make as much money, nor would my parents be able to introduce me as their “son the doctor.” But I would be content spending more time doing what I enjoyed.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Do you practice as a team member? How is your team defined? Is it made up solely of physicians? Does it include mid-level providers? Does it extend to mental health and social service providers in your office? Do you consider nonproviders such as receptionists as team members? Do you consider the whole office “your team”? Or, is it a smaller team with just yourself and one or two other physicians along with a mid-level provider or two?
There has been a lot written about primary care teams as a natural consequence of the medical home model. In an article in AAP News, Gonzalo J. Paz-Soldán, MD, a member of the American Academy of Pediatrics Council on Community Pediatrics and regional executive medical director, pediatrics, at Reliant Medical Group, Worcester, Mass., suggests that pediatricians should be taking on leadership roles in directing these teams. He claims that in addition to improving the “quality, value, patient experience,” our leadership also will benefit “provider and staff wellness and engagement.” In other words, taking charge will return the joy of pediatrics, and make us more resilient in the face of burnout.
It’s hard to argue with the notion that having more control improves our chances of satisfaction. Most of us who owned and ran our own small practices will tell you that when we were captains of the ship, those were our most rewarding and productive years.
However, assuming a leadership in a large multilevel team of providers and support staff is another story. As Dr. Paz-Soldán observes, most of us were not trained for leadership roles. I would add that the path to medical school does not select for those skills or interest. In addition to requiring a certain set of skill and aptitudes that we may not have, leadership demands a substantial time commitment.
Leading means attending what are often poorly conceived meetings (the topic for a future Letters from Maine), and receiving and writing emails – none of which involve actually taking care of patients. Like it or not, the ugly truth is that seeing patients is what generates our bottom lines. Time spent going to meetings and communicating with your teams members cannot be considered “billable hours.”
So here is our dilemma: Do we abandon the solo and small group practice model, sell out to large entities, lose control of our professional destiny, and spend our time grousing about it? Or
There are a few saintly and gifted physicians who have the skills, energy, and commitment to become leaders and still spend enough time seeing patients to satisfy both their emotional and financial professional needs. However, in my experience, when physicians move into leadership roles, the additional responsibilities cannibalize their commitment to patient care and the skills that made them talented physicians.
Given my aversion to meetings and my disinterest in organization on a large scale, I think if I were a college student considering a career taking care of children, I would take a hard look at becoming a nurse practitioner or physician’s assistant. I might not make as much money, nor would my parents be able to introduce me as their “son the doctor.” But I would be content spending more time doing what I enjoyed.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Long-term specialist care reduces post-RYGB anemia risk
Patients who underwent Roux-en-Y gastric bypass surgery (RYGB) without long-term bariatric specialist follow-up experienced a significantly higher rate of anemia at 10 years than did patients who had such specialist follow-up, according to findings from a database review.
Among 74 patients available for analysis – 58 men and 16 women with a mean age of 51 years who underwent RYGB at a single Veterans Affairs medical center between 2002 and 2006 – the mean rate of preoperative anemia was 20% (15 patients). The rate increased to 28% (21 patients) at 1 year, 31% (23 patients) at 5 years, and 47% (35 patients) at 10 years, according to a research letter by Gao Linda Chen, MD, and her colleagues in the surgical service of the VA Palo Alto (Calif.) Health Care System (JAMA Surg. 2017. Sep 20. doi: 10.1001/jamasurg.2017.3158).
Among 58 patients with no bariatric specialist follow-up after 5 years, the anemia rate increased from 22% (13 patients) before surgery to 57% (33 patients) at 10 years, while the corresponding rates for those with specialty follow-up were 19% (3 patients) and 13% (2 patients). After adjustment for preoperative anemia, those without specialist follow-up had significantly higher odds of anemia at 10 years (odds ratio, 6.1).
“Long-term complications of RYGB, such as anemia, may go unrecognized by nonbariatric specialists,” the investigators wrote, noting that the high rates of anemia at 10 years “may reflect a mixed vitamin and mineral deficiency, because patients had normocytic anemia.
“Our study suggests that follow-up with bariatric specialists more than 5 years after surgery, rather than with specialists with no bariatric expertise, can decrease long-term anemia risk,” they continued. “This finding may demonstrate the bariatric specialist’s specific understanding of the long-term risk for nutritional deficiency after RYGB and the importance of vitamin and mineral supplementation.”
The findings suggest a bariatric team approach with planning for long-term follow-up. “We implemented a hub-and-spoke model for bariatric care, including health care specialist education, in which the bariatric team communicates regularly with the patient’s primary care clinician before and after surgery.”
Although the study is limited by small sample size, the findings nevertheless underscore that “long-term follow-up should be an integral part of bariatric programs, and additional studies are needed to identify potential barriers to successful follow-up,” they concluded.
The authors reported having no disclosures.
Patients who underwent Roux-en-Y gastric bypass surgery (RYGB) without long-term bariatric specialist follow-up experienced a significantly higher rate of anemia at 10 years than did patients who had such specialist follow-up, according to findings from a database review.
Among 74 patients available for analysis – 58 men and 16 women with a mean age of 51 years who underwent RYGB at a single Veterans Affairs medical center between 2002 and 2006 – the mean rate of preoperative anemia was 20% (15 patients). The rate increased to 28% (21 patients) at 1 year, 31% (23 patients) at 5 years, and 47% (35 patients) at 10 years, according to a research letter by Gao Linda Chen, MD, and her colleagues in the surgical service of the VA Palo Alto (Calif.) Health Care System (JAMA Surg. 2017. Sep 20. doi: 10.1001/jamasurg.2017.3158).
Among 58 patients with no bariatric specialist follow-up after 5 years, the anemia rate increased from 22% (13 patients) before surgery to 57% (33 patients) at 10 years, while the corresponding rates for those with specialty follow-up were 19% (3 patients) and 13% (2 patients). After adjustment for preoperative anemia, those without specialist follow-up had significantly higher odds of anemia at 10 years (odds ratio, 6.1).
“Long-term complications of RYGB, such as anemia, may go unrecognized by nonbariatric specialists,” the investigators wrote, noting that the high rates of anemia at 10 years “may reflect a mixed vitamin and mineral deficiency, because patients had normocytic anemia.
“Our study suggests that follow-up with bariatric specialists more than 5 years after surgery, rather than with specialists with no bariatric expertise, can decrease long-term anemia risk,” they continued. “This finding may demonstrate the bariatric specialist’s specific understanding of the long-term risk for nutritional deficiency after RYGB and the importance of vitamin and mineral supplementation.”
The findings suggest a bariatric team approach with planning for long-term follow-up. “We implemented a hub-and-spoke model for bariatric care, including health care specialist education, in which the bariatric team communicates regularly with the patient’s primary care clinician before and after surgery.”
Although the study is limited by small sample size, the findings nevertheless underscore that “long-term follow-up should be an integral part of bariatric programs, and additional studies are needed to identify potential barriers to successful follow-up,” they concluded.
The authors reported having no disclosures.
Patients who underwent Roux-en-Y gastric bypass surgery (RYGB) without long-term bariatric specialist follow-up experienced a significantly higher rate of anemia at 10 years than did patients who had such specialist follow-up, according to findings from a database review.
Among 74 patients available for analysis – 58 men and 16 women with a mean age of 51 years who underwent RYGB at a single Veterans Affairs medical center between 2002 and 2006 – the mean rate of preoperative anemia was 20% (15 patients). The rate increased to 28% (21 patients) at 1 year, 31% (23 patients) at 5 years, and 47% (35 patients) at 10 years, according to a research letter by Gao Linda Chen, MD, and her colleagues in the surgical service of the VA Palo Alto (Calif.) Health Care System (JAMA Surg. 2017. Sep 20. doi: 10.1001/jamasurg.2017.3158).
Among 58 patients with no bariatric specialist follow-up after 5 years, the anemia rate increased from 22% (13 patients) before surgery to 57% (33 patients) at 10 years, while the corresponding rates for those with specialty follow-up were 19% (3 patients) and 13% (2 patients). After adjustment for preoperative anemia, those without specialist follow-up had significantly higher odds of anemia at 10 years (odds ratio, 6.1).
“Long-term complications of RYGB, such as anemia, may go unrecognized by nonbariatric specialists,” the investigators wrote, noting that the high rates of anemia at 10 years “may reflect a mixed vitamin and mineral deficiency, because patients had normocytic anemia.
“Our study suggests that follow-up with bariatric specialists more than 5 years after surgery, rather than with specialists with no bariatric expertise, can decrease long-term anemia risk,” they continued. “This finding may demonstrate the bariatric specialist’s specific understanding of the long-term risk for nutritional deficiency after RYGB and the importance of vitamin and mineral supplementation.”
The findings suggest a bariatric team approach with planning for long-term follow-up. “We implemented a hub-and-spoke model for bariatric care, including health care specialist education, in which the bariatric team communicates regularly with the patient’s primary care clinician before and after surgery.”
Although the study is limited by small sample size, the findings nevertheless underscore that “long-term follow-up should be an integral part of bariatric programs, and additional studies are needed to identify potential barriers to successful follow-up,” they concluded.
The authors reported having no disclosures.
FROM JAMA SURGERY
Key clinical point:
Major finding: RYGB patients without specialist follow-up had significantly higher odds of anemia at 10 years (adjusted odds ratio, 6.1).
Data source: A retrospective review of 74 patients from a prospective 10-year database.
Disclosures: The authors reported having no disclosures.
Pediatric Dermatology Consult - October 2017
Pyogenic granuloma
BY ALLISON HAN AND LAWRENCE F. EICHENFIELD, MD
Frontline Medical News
Pyogenic granuloma (PG), also known as lobular capillary hemangioma, is a benign, acquired vascular neoplasm of the skin and mucous membranes, and is fairly commonly found in children.1 Though most variants are superficial, PGs rarely may be discovered in subcutaneous, dermal, or satellite locations as well.2 Despite its name, no infectious or granulomatous disorder association with the vascular tumor has been discovered.
PGs are characterized by small, erythematous to purple papules that rapidly grow to become pedunculated or sessile within weeks, and then stabilize. They may bleed profusely because of their friable vascular nature, ulcerate, and crust.3 They rarely resolve on their own, thus, removal frequently is sought.4 PGs most commonly develop on the head and neck, and slightly less commonly on the fingers, periungual areas, upper extremities, lips, gingiva, and conjunctiva. Most PGs grow to about 1 to 10 mm.5
Histologically, PGs are organized in a characteristic lobular pattern of hyperplastic capillary clusters after which they are named (lobular capillary hemangioma). Fibrous bands separate the lobules. Mitotic activity is often seen, likely reflecting the rapid growth of the tumor.2 Immunohistochemistry staining is notably negative for glucose transporter 1 (GLUT-1), unlike hemangiomas, which aids in differentiating the two lesions.6
The pathogenesis of PGs is poorly understood; some hypothesize that a traumatic event, such as an insect bite, may trigger aberrant overgrowth of granulation tissue, but this theory is contested as many PGs appear to arise de novo.5 PGs have a tendency to develop within vascular lesions, suggesting an angiogenic stimuli of development, and increased expression of angiogenic growth factors (vascular endothelial growth factor and mitogen-activated protein kinase pathways) have been found in PGs.7,8
PGs also arise frequently during pregnancy and resolve after childbirth, leading many to support a causal role of estrogen in PG development. A link between both steroid hormone and angiogenesis may exist, as a beta isoform of estrogen receptor has been discovered to have consistent expression in a variety of vascular proliferations, possibly underlying PG pathogenesis.2
Drug-induced cases of PGs have been reported as well, with use of systemic medications such as acitretin, human immunodeficiency virus protease inhibitors, and epidermal growth factor receptor inhibitors.9
Diagnosis and differential
The diagnosis of PGs is based on the characteristic history of a rapidly growing, red to purple nodule that frequently bleeds and often ulcerates, accompanied by the physical findings of a typical exophytic, friable, vascular lesion. Patients often present with the “band aid sign,” an irritated portion of skin from the adhesive of bandages worn to protect the bleeding lesion.
The classic history of profuse and recurrent bleeding with little agitation often enables differentiation of PG from other disorders. In young infants, PGs may look similar to infantile hemangiomas, however hemangiomas regress and involute spontaneously unlike PGs.10 Other disorders that may be differentiated from PGs by history include Spitz nevi, glomus tumors, and warts. Melanoma in children may be amelanotic and present as red papules or nodules as well.11 An association between Bartonella infection and PGs had been questioned in the past because of reported increased rates of Bartonella seropositivity in patients, but this has since been debunked.12
Treatment
Almost all PGs undergo treatment; 85%-90% of PGs are treated by localized numbing, followed by superficial excision and electrodessication of the base.13 This technique allows the PG to be removed in less than 5 minutes and avoids suture use. Alternative treatments include surgical excision, pulsed dye laser, cryotherapy with liquid nitrogen, timolol solution, imiquimod, or a combination of methods.3,4,5 Methods that produce tissue for histopathologic analysis are ideal to rule out malignancy or other lesions that may mimic PGs such as Spitz nevi. Pulsed dye laser offers low recurrence, but often requires multiple treatments, and young children may not tolerate the treatment well. Cryotherapy has few side effects, but has higher recurrence rates and requires multiple treatment sessions.14
Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego, as well as vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Allison Han is a medical student at the university. Neither Dr. Eichenfield nor Ms. Han have any relevant financial disclosures. Email them at [email protected].
References
1. Br J Dermatol. 2014;171(3):466-73.
2. Am J Dermatopathol. 2007;29(4):408-11.
3. J Plast Reconstr Aesthet Surg. 2011;64(9):1216-20.
4. Br J Dermatol. 2014;171(6):1537-8.
5. Pediatr Dermatol. 2004;21(1):10-3.
6. Pediatr Dermatol. 2009;26(3):323-7.
7. J Am Acad Dermatol. 2000;42(2 Pt 1):275-9.
8. J Am Acad Dermatol. 2001;44(2):193-7.
9. Br J Dermatol. 2010;163(5):941-53.
10. Pediatrics. 1992;90(6):989-91.
11. J Am Acad Dermatol. 2013;68(6):913-25.
12. J Am Acad Dermatol. 2005;53(6):1065-6.
13. “Hurwitz Clinical Pediatric Dermatology,” 4th Edition: A Textbook of Skin Disorders of Childhood and Adolescence (New York: Elsevier Health Sciences, 2011).
14. Dermatol Surg. 2013;39(8):1137-46.
Pyogenic granuloma
BY ALLISON HAN AND LAWRENCE F. EICHENFIELD, MD
Frontline Medical News
Pyogenic granuloma (PG), also known as lobular capillary hemangioma, is a benign, acquired vascular neoplasm of the skin and mucous membranes, and is fairly commonly found in children.1 Though most variants are superficial, PGs rarely may be discovered in subcutaneous, dermal, or satellite locations as well.2 Despite its name, no infectious or granulomatous disorder association with the vascular tumor has been discovered.
PGs are characterized by small, erythematous to purple papules that rapidly grow to become pedunculated or sessile within weeks, and then stabilize. They may bleed profusely because of their friable vascular nature, ulcerate, and crust.3 They rarely resolve on their own, thus, removal frequently is sought.4 PGs most commonly develop on the head and neck, and slightly less commonly on the fingers, periungual areas, upper extremities, lips, gingiva, and conjunctiva. Most PGs grow to about 1 to 10 mm.5
Histologically, PGs are organized in a characteristic lobular pattern of hyperplastic capillary clusters after which they are named (lobular capillary hemangioma). Fibrous bands separate the lobules. Mitotic activity is often seen, likely reflecting the rapid growth of the tumor.2 Immunohistochemistry staining is notably negative for glucose transporter 1 (GLUT-1), unlike hemangiomas, which aids in differentiating the two lesions.6
The pathogenesis of PGs is poorly understood; some hypothesize that a traumatic event, such as an insect bite, may trigger aberrant overgrowth of granulation tissue, but this theory is contested as many PGs appear to arise de novo.5 PGs have a tendency to develop within vascular lesions, suggesting an angiogenic stimuli of development, and increased expression of angiogenic growth factors (vascular endothelial growth factor and mitogen-activated protein kinase pathways) have been found in PGs.7,8
PGs also arise frequently during pregnancy and resolve after childbirth, leading many to support a causal role of estrogen in PG development. A link between both steroid hormone and angiogenesis may exist, as a beta isoform of estrogen receptor has been discovered to have consistent expression in a variety of vascular proliferations, possibly underlying PG pathogenesis.2
Drug-induced cases of PGs have been reported as well, with use of systemic medications such as acitretin, human immunodeficiency virus protease inhibitors, and epidermal growth factor receptor inhibitors.9
Diagnosis and differential
The diagnosis of PGs is based on the characteristic history of a rapidly growing, red to purple nodule that frequently bleeds and often ulcerates, accompanied by the physical findings of a typical exophytic, friable, vascular lesion. Patients often present with the “band aid sign,” an irritated portion of skin from the adhesive of bandages worn to protect the bleeding lesion.
The classic history of profuse and recurrent bleeding with little agitation often enables differentiation of PG from other disorders. In young infants, PGs may look similar to infantile hemangiomas, however hemangiomas regress and involute spontaneously unlike PGs.10 Other disorders that may be differentiated from PGs by history include Spitz nevi, glomus tumors, and warts. Melanoma in children may be amelanotic and present as red papules or nodules as well.11 An association between Bartonella infection and PGs had been questioned in the past because of reported increased rates of Bartonella seropositivity in patients, but this has since been debunked.12
Treatment
Almost all PGs undergo treatment; 85%-90% of PGs are treated by localized numbing, followed by superficial excision and electrodessication of the base.13 This technique allows the PG to be removed in less than 5 minutes and avoids suture use. Alternative treatments include surgical excision, pulsed dye laser, cryotherapy with liquid nitrogen, timolol solution, imiquimod, or a combination of methods.3,4,5 Methods that produce tissue for histopathologic analysis are ideal to rule out malignancy or other lesions that may mimic PGs such as Spitz nevi. Pulsed dye laser offers low recurrence, but often requires multiple treatments, and young children may not tolerate the treatment well. Cryotherapy has few side effects, but has higher recurrence rates and requires multiple treatment sessions.14
Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego, as well as vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Allison Han is a medical student at the university. Neither Dr. Eichenfield nor Ms. Han have any relevant financial disclosures. Email them at [email protected].
References
1. Br J Dermatol. 2014;171(3):466-73.
2. Am J Dermatopathol. 2007;29(4):408-11.
3. J Plast Reconstr Aesthet Surg. 2011;64(9):1216-20.
4. Br J Dermatol. 2014;171(6):1537-8.
5. Pediatr Dermatol. 2004;21(1):10-3.
6. Pediatr Dermatol. 2009;26(3):323-7.
7. J Am Acad Dermatol. 2000;42(2 Pt 1):275-9.
8. J Am Acad Dermatol. 2001;44(2):193-7.
9. Br J Dermatol. 2010;163(5):941-53.
10. Pediatrics. 1992;90(6):989-91.
11. J Am Acad Dermatol. 2013;68(6):913-25.
12. J Am Acad Dermatol. 2005;53(6):1065-6.
13. “Hurwitz Clinical Pediatric Dermatology,” 4th Edition: A Textbook of Skin Disorders of Childhood and Adolescence (New York: Elsevier Health Sciences, 2011).
14. Dermatol Surg. 2013;39(8):1137-46.
Pyogenic granuloma
BY ALLISON HAN AND LAWRENCE F. EICHENFIELD, MD
Frontline Medical News
Pyogenic granuloma (PG), also known as lobular capillary hemangioma, is a benign, acquired vascular neoplasm of the skin and mucous membranes, and is fairly commonly found in children.1 Though most variants are superficial, PGs rarely may be discovered in subcutaneous, dermal, or satellite locations as well.2 Despite its name, no infectious or granulomatous disorder association with the vascular tumor has been discovered.
PGs are characterized by small, erythematous to purple papules that rapidly grow to become pedunculated or sessile within weeks, and then stabilize. They may bleed profusely because of their friable vascular nature, ulcerate, and crust.3 They rarely resolve on their own, thus, removal frequently is sought.4 PGs most commonly develop on the head and neck, and slightly less commonly on the fingers, periungual areas, upper extremities, lips, gingiva, and conjunctiva. Most PGs grow to about 1 to 10 mm.5
Histologically, PGs are organized in a characteristic lobular pattern of hyperplastic capillary clusters after which they are named (lobular capillary hemangioma). Fibrous bands separate the lobules. Mitotic activity is often seen, likely reflecting the rapid growth of the tumor.2 Immunohistochemistry staining is notably negative for glucose transporter 1 (GLUT-1), unlike hemangiomas, which aids in differentiating the two lesions.6
The pathogenesis of PGs is poorly understood; some hypothesize that a traumatic event, such as an insect bite, may trigger aberrant overgrowth of granulation tissue, but this theory is contested as many PGs appear to arise de novo.5 PGs have a tendency to develop within vascular lesions, suggesting an angiogenic stimuli of development, and increased expression of angiogenic growth factors (vascular endothelial growth factor and mitogen-activated protein kinase pathways) have been found in PGs.7,8
PGs also arise frequently during pregnancy and resolve after childbirth, leading many to support a causal role of estrogen in PG development. A link between both steroid hormone and angiogenesis may exist, as a beta isoform of estrogen receptor has been discovered to have consistent expression in a variety of vascular proliferations, possibly underlying PG pathogenesis.2
Drug-induced cases of PGs have been reported as well, with use of systemic medications such as acitretin, human immunodeficiency virus protease inhibitors, and epidermal growth factor receptor inhibitors.9
Diagnosis and differential
The diagnosis of PGs is based on the characteristic history of a rapidly growing, red to purple nodule that frequently bleeds and often ulcerates, accompanied by the physical findings of a typical exophytic, friable, vascular lesion. Patients often present with the “band aid sign,” an irritated portion of skin from the adhesive of bandages worn to protect the bleeding lesion.
The classic history of profuse and recurrent bleeding with little agitation often enables differentiation of PG from other disorders. In young infants, PGs may look similar to infantile hemangiomas, however hemangiomas regress and involute spontaneously unlike PGs.10 Other disorders that may be differentiated from PGs by history include Spitz nevi, glomus tumors, and warts. Melanoma in children may be amelanotic and present as red papules or nodules as well.11 An association between Bartonella infection and PGs had been questioned in the past because of reported increased rates of Bartonella seropositivity in patients, but this has since been debunked.12
Treatment
Almost all PGs undergo treatment; 85%-90% of PGs are treated by localized numbing, followed by superficial excision and electrodessication of the base.13 This technique allows the PG to be removed in less than 5 minutes and avoids suture use. Alternative treatments include surgical excision, pulsed dye laser, cryotherapy with liquid nitrogen, timolol solution, imiquimod, or a combination of methods.3,4,5 Methods that produce tissue for histopathologic analysis are ideal to rule out malignancy or other lesions that may mimic PGs such as Spitz nevi. Pulsed dye laser offers low recurrence, but often requires multiple treatments, and young children may not tolerate the treatment well. Cryotherapy has few side effects, but has higher recurrence rates and requires multiple treatment sessions.14
Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego, as well as vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Allison Han is a medical student at the university. Neither Dr. Eichenfield nor Ms. Han have any relevant financial disclosures. Email them at [email protected].
References
1. Br J Dermatol. 2014;171(3):466-73.
2. Am J Dermatopathol. 2007;29(4):408-11.
3. J Plast Reconstr Aesthet Surg. 2011;64(9):1216-20.
4. Br J Dermatol. 2014;171(6):1537-8.
5. Pediatr Dermatol. 2004;21(1):10-3.
6. Pediatr Dermatol. 2009;26(3):323-7.
7. J Am Acad Dermatol. 2000;42(2 Pt 1):275-9.
8. J Am Acad Dermatol. 2001;44(2):193-7.
9. Br J Dermatol. 2010;163(5):941-53.
10. Pediatrics. 1992;90(6):989-91.
11. J Am Acad Dermatol. 2013;68(6):913-25.
12. J Am Acad Dermatol. 2005;53(6):1065-6.
13. “Hurwitz Clinical Pediatric Dermatology,” 4th Edition: A Textbook of Skin Disorders of Childhood and Adolescence (New York: Elsevier Health Sciences, 2011).
14. Dermatol Surg. 2013;39(8):1137-46.
A 7-year-old healthy female presents to the dermatology clinic for evaluation of a bump on her lower lip that has been present for 3 months. It started as a small red papule and within a couple months rapidly increased in size, but now has stabilized. She denies pain and itching, but she notes that it frequently bleeds, and that the bleeding can be difficult to stop. She denies any trauma to the area. Review of systems was otherwise negative.
On examination, the patient is a well-developed, healthy appearing female. In the middle of her lower lip, there is a 1-cm pedunculated, raspberry-like exophytic nodule. It is reddish-purple with slight ulceration at the surface. There is no active bleeding. The remainder of the physical examination is normal.
Adding bortezomib to R-CHOP didn’t improve survival in diffuse large B-cell lymphoma
, findings from the phase-2 PYRAMID trial showed.
When the proteasome inhibitor bortezomib was combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated non–germinal center B-cell–like (non-GCB) DLBCL, a significant improvement in progression-free survival (PFS) was not observed.
There also was no increase in 2-year PFS among patients treated with the combination of bortezomib plus R-CHOP (VR-CHOP), according to findings from the open-label, randomized study published in the Journal of Clinical Oncology (2017 Sep 1. doi: 10.1200/JCO.2017.73.2784).
“A potential reason for the lack of benefit with VR-CHOP was that only two doses of bortezomib were given per 21-day cycle, whereas the standard schedule for bortezomib in multiple myeloma is four doses per cycle on days 1, 4, 8, and 11,” wrote John P. Leonard, MD, of Weill Cornell Medicine and New York Presbyterian Hospital, New York, and his colleagues. “In this study, treatment duration was limited to six 21-day cycles of R-CHOP.”
The authors noted that previous research has demonstrated the feasibility of using VR-CHOP and similar immunochemotherapy regimens in DLBCL. In the current PYRAMID (Personalized Lymphoma Therapy: Randomized Study of Proteasome Inhibition in Non-GCB DLBCL) phase 2 trial, VR-CHOP was compared with R-CHOP in 206 patients with previously untreated non-GCB DLBCL who were selected by real-time subtyping conducted or confirmed at a central laboratory that used the Hans algorithm.
The cohort was randomized to receive six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4, and the primary endpoint was PFS.
The hazard ratio (HR) for PFS was 0.73 (90% confidence interval, 0.43-1.24) and favored VR-CHOP (P = .611), while the median PFS was not reached in either group. At 2 years, PFS was 77.6% with R-CHOP, versus 82.0% with VR-CHOP.
Among patients with high-intermediate/high International Prognostic Index (IPI) risk, those rates were 65.1% with R-CHOP, versus 72.4% with VR-CHOP (HR, 0.67; 90% CI, 0.34-1.29; P = .606). For those patients at low/low-intermediate IPI risk, the rates were 90.0% for R-CHOP, versus 88.9% for VR-CHOP (HR, 0.85; 90% CI, 0.35-2.10; P = .958).
The overall response rate was 98% for R-CHOP patients and 96% for VR-CHOP, with complete response rates of 49% and 56%, respectively.
Time to progression rates at 2 years were 79.8% for R-CHOP, versus 83.0% with VR-CHOP (HR, 0.79; 90% CI, 0.45-1.37; P = .767). While median overall survival was not reached in either arm, the HR for the entire cohort was 0.75 (90% CI, 0.38-1.45; P = .763). Two-year overall survival was 88.4% and 93.0%, respectively.
In the high-intermediate/high IPI score group, 2-year overall survival was 79.2% with R-CHOP, versus 92.1% with VR-CHOP (HR, 0.62; 90% CI, 0.25-1.42; P = .638), and for those with low/low-intermediate IPI risk scores, 97.7% versus 93.8% (HR, 1.02; 90% CI, 0.34-3.27; P = .999).
Millennium Pharmaceuticals supported the study. Dr. Leonard and several of the coauthors reported relationships with industry.
, findings from the phase-2 PYRAMID trial showed.
When the proteasome inhibitor bortezomib was combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated non–germinal center B-cell–like (non-GCB) DLBCL, a significant improvement in progression-free survival (PFS) was not observed.
There also was no increase in 2-year PFS among patients treated with the combination of bortezomib plus R-CHOP (VR-CHOP), according to findings from the open-label, randomized study published in the Journal of Clinical Oncology (2017 Sep 1. doi: 10.1200/JCO.2017.73.2784).
“A potential reason for the lack of benefit with VR-CHOP was that only two doses of bortezomib were given per 21-day cycle, whereas the standard schedule for bortezomib in multiple myeloma is four doses per cycle on days 1, 4, 8, and 11,” wrote John P. Leonard, MD, of Weill Cornell Medicine and New York Presbyterian Hospital, New York, and his colleagues. “In this study, treatment duration was limited to six 21-day cycles of R-CHOP.”
The authors noted that previous research has demonstrated the feasibility of using VR-CHOP and similar immunochemotherapy regimens in DLBCL. In the current PYRAMID (Personalized Lymphoma Therapy: Randomized Study of Proteasome Inhibition in Non-GCB DLBCL) phase 2 trial, VR-CHOP was compared with R-CHOP in 206 patients with previously untreated non-GCB DLBCL who were selected by real-time subtyping conducted or confirmed at a central laboratory that used the Hans algorithm.
The cohort was randomized to receive six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4, and the primary endpoint was PFS.
The hazard ratio (HR) for PFS was 0.73 (90% confidence interval, 0.43-1.24) and favored VR-CHOP (P = .611), while the median PFS was not reached in either group. At 2 years, PFS was 77.6% with R-CHOP, versus 82.0% with VR-CHOP.
Among patients with high-intermediate/high International Prognostic Index (IPI) risk, those rates were 65.1% with R-CHOP, versus 72.4% with VR-CHOP (HR, 0.67; 90% CI, 0.34-1.29; P = .606). For those patients at low/low-intermediate IPI risk, the rates were 90.0% for R-CHOP, versus 88.9% for VR-CHOP (HR, 0.85; 90% CI, 0.35-2.10; P = .958).
The overall response rate was 98% for R-CHOP patients and 96% for VR-CHOP, with complete response rates of 49% and 56%, respectively.
Time to progression rates at 2 years were 79.8% for R-CHOP, versus 83.0% with VR-CHOP (HR, 0.79; 90% CI, 0.45-1.37; P = .767). While median overall survival was not reached in either arm, the HR for the entire cohort was 0.75 (90% CI, 0.38-1.45; P = .763). Two-year overall survival was 88.4% and 93.0%, respectively.
In the high-intermediate/high IPI score group, 2-year overall survival was 79.2% with R-CHOP, versus 92.1% with VR-CHOP (HR, 0.62; 90% CI, 0.25-1.42; P = .638), and for those with low/low-intermediate IPI risk scores, 97.7% versus 93.8% (HR, 1.02; 90% CI, 0.34-3.27; P = .999).
Millennium Pharmaceuticals supported the study. Dr. Leonard and several of the coauthors reported relationships with industry.
, findings from the phase-2 PYRAMID trial showed.
When the proteasome inhibitor bortezomib was combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated non–germinal center B-cell–like (non-GCB) DLBCL, a significant improvement in progression-free survival (PFS) was not observed.
There also was no increase in 2-year PFS among patients treated with the combination of bortezomib plus R-CHOP (VR-CHOP), according to findings from the open-label, randomized study published in the Journal of Clinical Oncology (2017 Sep 1. doi: 10.1200/JCO.2017.73.2784).
“A potential reason for the lack of benefit with VR-CHOP was that only two doses of bortezomib were given per 21-day cycle, whereas the standard schedule for bortezomib in multiple myeloma is four doses per cycle on days 1, 4, 8, and 11,” wrote John P. Leonard, MD, of Weill Cornell Medicine and New York Presbyterian Hospital, New York, and his colleagues. “In this study, treatment duration was limited to six 21-day cycles of R-CHOP.”
The authors noted that previous research has demonstrated the feasibility of using VR-CHOP and similar immunochemotherapy regimens in DLBCL. In the current PYRAMID (Personalized Lymphoma Therapy: Randomized Study of Proteasome Inhibition in Non-GCB DLBCL) phase 2 trial, VR-CHOP was compared with R-CHOP in 206 patients with previously untreated non-GCB DLBCL who were selected by real-time subtyping conducted or confirmed at a central laboratory that used the Hans algorithm.
The cohort was randomized to receive six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4, and the primary endpoint was PFS.
The hazard ratio (HR) for PFS was 0.73 (90% confidence interval, 0.43-1.24) and favored VR-CHOP (P = .611), while the median PFS was not reached in either group. At 2 years, PFS was 77.6% with R-CHOP, versus 82.0% with VR-CHOP.
Among patients with high-intermediate/high International Prognostic Index (IPI) risk, those rates were 65.1% with R-CHOP, versus 72.4% with VR-CHOP (HR, 0.67; 90% CI, 0.34-1.29; P = .606). For those patients at low/low-intermediate IPI risk, the rates were 90.0% for R-CHOP, versus 88.9% for VR-CHOP (HR, 0.85; 90% CI, 0.35-2.10; P = .958).
The overall response rate was 98% for R-CHOP patients and 96% for VR-CHOP, with complete response rates of 49% and 56%, respectively.
Time to progression rates at 2 years were 79.8% for R-CHOP, versus 83.0% with VR-CHOP (HR, 0.79; 90% CI, 0.45-1.37; P = .767). While median overall survival was not reached in either arm, the HR for the entire cohort was 0.75 (90% CI, 0.38-1.45; P = .763). Two-year overall survival was 88.4% and 93.0%, respectively.
In the high-intermediate/high IPI score group, 2-year overall survival was 79.2% with R-CHOP, versus 92.1% with VR-CHOP (HR, 0.62; 90% CI, 0.25-1.42; P = .638), and for those with low/low-intermediate IPI risk scores, 97.7% versus 93.8% (HR, 1.02; 90% CI, 0.34-3.27; P = .999).
Millennium Pharmaceuticals supported the study. Dr. Leonard and several of the coauthors reported relationships with industry.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Bortezomib combined with R-CHOP did not improve outcomes significantly in diffuse large B-cell lymphoma.
Major finding: Two-year progression-free survival was 77.6% with R-CHOP, compared with 82.0% with VR-CHOP, a nonsignificant difference.
Data source: An open-label, randomized, phase 2 trial that compared VR-CHOP to R-CHOP in 206 patients with previously untreated non-GCB DLBCL.
Disclosures: Millennium Pharmaceuticals funded the study. Dr. Leonard and several of the coauthors reported relationships with industry.
Proposed MACRA participation threshold gets mixed reviews
Proposed changes to the Quality Payment Program (QPP) – the value-based payment program established by the Medicare Access and CHIP Reauthorization Act (MACRA) – are drawing mixed reactions from physicians.
A key component of the proposed update to the QPP is an expansion of the exemption threshold for the Merit-based Incentive Payment System (MIPS). Currently, physicians are exempt from MIPS if they bill $30,000 or less in Medicare Part B charges or have 100 or fewer Medicare patients. The proposal would increase the number of exempt physicians by raising the threshold to $90,000 or less in Part B charges or 200 or fewer Medicare patients.
Eligible clinicians and group practices that fall below the threshold can still voluntarily submit data, but they will not be scored for their participation in MIPS and will not be eligible for bonuses or face penalties for not meeting goals.
The expanded threshold proposal drew praise from the American Medical Association for exempting many small and rural practices from the requirements, but they also called on the agency to move more quickly in notifying physicians if they fall into the exempt category.
The American College of Surgeons expressed support for the changes to the threshold, adding that going forward the threshold should “be maintained at numbers no lower than that proposed for the 2018 performance period so that providers may have certainty of the criteria and their participation responsibilities from year to year.”
The American College of Cardiology supported the expansion of the low-volume threshold and encouraged the agency to review the levels annually.
But the Association of American Physicians & Surgeons suggested the volume threshold didn’t go far enough. “We ask that CMS consider a further widening of the threshold to all practices with 18 or fewer clinicians,” the group said in its comments on the proposal. “A threshold in terms of billing amounts and the number of patients creates an unhelpful incentive for physicians to turn away Medicare patients in order to qualify for the exemption.”
The group argued that larger practices can better absorb the cost of complying with MACRA regulations and basing participation on billing could create uncertainty due to fluctuations in billing from year-to-year.
Opt in option?
Several other groups sought a pathway for exempt physicians to opt into the program and take advantage of bonuses, especially those who had already prepared for the program based on the lower initial threshold.
“By raising the low-volume threshold and not offering an opt-in ability, CMS is further and needlessly delaying practices from payment based on value over volume, as well as the intent behind the establishment of virtual groups,” the American Academy of Family Physicians wrote in comments to the CMS.
The American Gastroenterological Association voiced its support for expanding the exclusion threshold and supported the idea of an opt-in, but called on the CMS to hold harmless those practices that opted in. “Clinicians and groups opting-in to the QPP should not be subject to negative payment adjustments,” AGA said in its comments to the CMS.
The American Academy of Dermatology Association supports the proposed low-volume threshold and called upon the CMS to allow those who want to participate to create a path to opt into MIPS.
The Endocrine Society supports the expansion of the threshold, but called on the CMS to provide a pathway for those who want to participate if they are otherwise excluded.
The American Osteopathic Association also called for a pathway for exempted physicians to opt in. And they cited two negative effects of expanding the threshold to a wider group of physicians. “First, it will result in wasted resources from practices that prepared for MIPS participation and are now unable to participate,” the association said in comments to the CMS. “Second, it will have the effect of dividing all practices into two levels: those that are incentivized to provide value-based care, and a significant number that are not eligible for such incentives.”
Individuals vs. groups
The American Congress of Obstetricians and Gynecologists (ACOG) supports the proposed threshold for individuals, but suggested changes for groups. “ACOG continues to believe that the threshold should only apply to individual clinicians and that CMS should develop a new, separate definition if the agency believes that groups should also have a low-volume threshold,” ACOG said in comments to the CMS. “Setting the low-volume threshold at both the individual and group level introduces unnecessary complexity into the program because other exclusions for MIPS only apply to individual clinicians.”
The Medical Group Management Association (MGMA), while supporting the general goal of reducing burden on small and solo practices, suggested it needed to be tweaked for the group setting.
“MGMA continues to question CMS’ application of the same threshold at both the clinician and group practice level,” the association said in its comments to the CMS. “This approach significantly disadvantages groups of clinicians who, in the aggregate, rarely care for Medicare patients, but include one or two members that actively participate in the program. MGMA urges CMS to extend its own logic behind setting a group practice equivalent for the non-patient-facing definition by exempting group practices when 75% or more of the national provider identifiers who bill under the group’s tax identification number meet the threshold on an individual basis.”
Expansion goes too far
But the AMGA, which represents group practices, called the new threshold “counterproductive” in its comment letter and suggested that the CMS should be lowering the threshold, not raising it.
AMGA noted that eligible clinicians who do not meet the threshold, but who are providing high-value care as defined by the QPP, are “forced to leave higher reimbursement rates on the table; these could be considerable over time.”
In addition, AMGA said that expanding the exemption decreases the money available for those who are required to participate. The CMS estimates in the proposed rule that in payment year 2019, $1.333 billion would be paid to top performers (including $500 million in exceptional performance bonus payments), but under the newest proposal, that number drops to $673 million (including $500 million in exceptional performance bonus payments). This will translate to a 0.3% bump in payment in 2020.
“The effect of eliminating of two-thirds of eligible clinicians from the MIPS formula is to financially undermine participating clinicians,” AMGA said in comments to the CMS. “They effectively lose by winning.”
Proposed changes to the Quality Payment Program (QPP) – the value-based payment program established by the Medicare Access and CHIP Reauthorization Act (MACRA) – are drawing mixed reactions from physicians.
A key component of the proposed update to the QPP is an expansion of the exemption threshold for the Merit-based Incentive Payment System (MIPS). Currently, physicians are exempt from MIPS if they bill $30,000 or less in Medicare Part B charges or have 100 or fewer Medicare patients. The proposal would increase the number of exempt physicians by raising the threshold to $90,000 or less in Part B charges or 200 or fewer Medicare patients.
Eligible clinicians and group practices that fall below the threshold can still voluntarily submit data, but they will not be scored for their participation in MIPS and will not be eligible for bonuses or face penalties for not meeting goals.
The expanded threshold proposal drew praise from the American Medical Association for exempting many small and rural practices from the requirements, but they also called on the agency to move more quickly in notifying physicians if they fall into the exempt category.
The American College of Surgeons expressed support for the changes to the threshold, adding that going forward the threshold should “be maintained at numbers no lower than that proposed for the 2018 performance period so that providers may have certainty of the criteria and their participation responsibilities from year to year.”
The American College of Cardiology supported the expansion of the low-volume threshold and encouraged the agency to review the levels annually.
But the Association of American Physicians & Surgeons suggested the volume threshold didn’t go far enough. “We ask that CMS consider a further widening of the threshold to all practices with 18 or fewer clinicians,” the group said in its comments on the proposal. “A threshold in terms of billing amounts and the number of patients creates an unhelpful incentive for physicians to turn away Medicare patients in order to qualify for the exemption.”
The group argued that larger practices can better absorb the cost of complying with MACRA regulations and basing participation on billing could create uncertainty due to fluctuations in billing from year-to-year.
Opt in option?
Several other groups sought a pathway for exempt physicians to opt into the program and take advantage of bonuses, especially those who had already prepared for the program based on the lower initial threshold.
“By raising the low-volume threshold and not offering an opt-in ability, CMS is further and needlessly delaying practices from payment based on value over volume, as well as the intent behind the establishment of virtual groups,” the American Academy of Family Physicians wrote in comments to the CMS.
The American Gastroenterological Association voiced its support for expanding the exclusion threshold and supported the idea of an opt-in, but called on the CMS to hold harmless those practices that opted in. “Clinicians and groups opting-in to the QPP should not be subject to negative payment adjustments,” AGA said in its comments to the CMS.
The American Academy of Dermatology Association supports the proposed low-volume threshold and called upon the CMS to allow those who want to participate to create a path to opt into MIPS.
The Endocrine Society supports the expansion of the threshold, but called on the CMS to provide a pathway for those who want to participate if they are otherwise excluded.
The American Osteopathic Association also called for a pathway for exempted physicians to opt in. And they cited two negative effects of expanding the threshold to a wider group of physicians. “First, it will result in wasted resources from practices that prepared for MIPS participation and are now unable to participate,” the association said in comments to the CMS. “Second, it will have the effect of dividing all practices into two levels: those that are incentivized to provide value-based care, and a significant number that are not eligible for such incentives.”
Individuals vs. groups
The American Congress of Obstetricians and Gynecologists (ACOG) supports the proposed threshold for individuals, but suggested changes for groups. “ACOG continues to believe that the threshold should only apply to individual clinicians and that CMS should develop a new, separate definition if the agency believes that groups should also have a low-volume threshold,” ACOG said in comments to the CMS. “Setting the low-volume threshold at both the individual and group level introduces unnecessary complexity into the program because other exclusions for MIPS only apply to individual clinicians.”
The Medical Group Management Association (MGMA), while supporting the general goal of reducing burden on small and solo practices, suggested it needed to be tweaked for the group setting.
“MGMA continues to question CMS’ application of the same threshold at both the clinician and group practice level,” the association said in its comments to the CMS. “This approach significantly disadvantages groups of clinicians who, in the aggregate, rarely care for Medicare patients, but include one or two members that actively participate in the program. MGMA urges CMS to extend its own logic behind setting a group practice equivalent for the non-patient-facing definition by exempting group practices when 75% or more of the national provider identifiers who bill under the group’s tax identification number meet the threshold on an individual basis.”
Expansion goes too far
But the AMGA, which represents group practices, called the new threshold “counterproductive” in its comment letter and suggested that the CMS should be lowering the threshold, not raising it.
AMGA noted that eligible clinicians who do not meet the threshold, but who are providing high-value care as defined by the QPP, are “forced to leave higher reimbursement rates on the table; these could be considerable over time.”
In addition, AMGA said that expanding the exemption decreases the money available for those who are required to participate. The CMS estimates in the proposed rule that in payment year 2019, $1.333 billion would be paid to top performers (including $500 million in exceptional performance bonus payments), but under the newest proposal, that number drops to $673 million (including $500 million in exceptional performance bonus payments). This will translate to a 0.3% bump in payment in 2020.
“The effect of eliminating of two-thirds of eligible clinicians from the MIPS formula is to financially undermine participating clinicians,” AMGA said in comments to the CMS. “They effectively lose by winning.”
Proposed changes to the Quality Payment Program (QPP) – the value-based payment program established by the Medicare Access and CHIP Reauthorization Act (MACRA) – are drawing mixed reactions from physicians.
A key component of the proposed update to the QPP is an expansion of the exemption threshold for the Merit-based Incentive Payment System (MIPS). Currently, physicians are exempt from MIPS if they bill $30,000 or less in Medicare Part B charges or have 100 or fewer Medicare patients. The proposal would increase the number of exempt physicians by raising the threshold to $90,000 or less in Part B charges or 200 or fewer Medicare patients.
Eligible clinicians and group practices that fall below the threshold can still voluntarily submit data, but they will not be scored for their participation in MIPS and will not be eligible for bonuses or face penalties for not meeting goals.
The expanded threshold proposal drew praise from the American Medical Association for exempting many small and rural practices from the requirements, but they also called on the agency to move more quickly in notifying physicians if they fall into the exempt category.
The American College of Surgeons expressed support for the changes to the threshold, adding that going forward the threshold should “be maintained at numbers no lower than that proposed for the 2018 performance period so that providers may have certainty of the criteria and their participation responsibilities from year to year.”
The American College of Cardiology supported the expansion of the low-volume threshold and encouraged the agency to review the levels annually.
But the Association of American Physicians & Surgeons suggested the volume threshold didn’t go far enough. “We ask that CMS consider a further widening of the threshold to all practices with 18 or fewer clinicians,” the group said in its comments on the proposal. “A threshold in terms of billing amounts and the number of patients creates an unhelpful incentive for physicians to turn away Medicare patients in order to qualify for the exemption.”
The group argued that larger practices can better absorb the cost of complying with MACRA regulations and basing participation on billing could create uncertainty due to fluctuations in billing from year-to-year.
Opt in option?
Several other groups sought a pathway for exempt physicians to opt into the program and take advantage of bonuses, especially those who had already prepared for the program based on the lower initial threshold.
“By raising the low-volume threshold and not offering an opt-in ability, CMS is further and needlessly delaying practices from payment based on value over volume, as well as the intent behind the establishment of virtual groups,” the American Academy of Family Physicians wrote in comments to the CMS.
The American Gastroenterological Association voiced its support for expanding the exclusion threshold and supported the idea of an opt-in, but called on the CMS to hold harmless those practices that opted in. “Clinicians and groups opting-in to the QPP should not be subject to negative payment adjustments,” AGA said in its comments to the CMS.
The American Academy of Dermatology Association supports the proposed low-volume threshold and called upon the CMS to allow those who want to participate to create a path to opt into MIPS.
The Endocrine Society supports the expansion of the threshold, but called on the CMS to provide a pathway for those who want to participate if they are otherwise excluded.
The American Osteopathic Association also called for a pathway for exempted physicians to opt in. And they cited two negative effects of expanding the threshold to a wider group of physicians. “First, it will result in wasted resources from practices that prepared for MIPS participation and are now unable to participate,” the association said in comments to the CMS. “Second, it will have the effect of dividing all practices into two levels: those that are incentivized to provide value-based care, and a significant number that are not eligible for such incentives.”
Individuals vs. groups
The American Congress of Obstetricians and Gynecologists (ACOG) supports the proposed threshold for individuals, but suggested changes for groups. “ACOG continues to believe that the threshold should only apply to individual clinicians and that CMS should develop a new, separate definition if the agency believes that groups should also have a low-volume threshold,” ACOG said in comments to the CMS. “Setting the low-volume threshold at both the individual and group level introduces unnecessary complexity into the program because other exclusions for MIPS only apply to individual clinicians.”
The Medical Group Management Association (MGMA), while supporting the general goal of reducing burden on small and solo practices, suggested it needed to be tweaked for the group setting.
“MGMA continues to question CMS’ application of the same threshold at both the clinician and group practice level,” the association said in its comments to the CMS. “This approach significantly disadvantages groups of clinicians who, in the aggregate, rarely care for Medicare patients, but include one or two members that actively participate in the program. MGMA urges CMS to extend its own logic behind setting a group practice equivalent for the non-patient-facing definition by exempting group practices when 75% or more of the national provider identifiers who bill under the group’s tax identification number meet the threshold on an individual basis.”
Expansion goes too far
But the AMGA, which represents group practices, called the new threshold “counterproductive” in its comment letter and suggested that the CMS should be lowering the threshold, not raising it.
AMGA noted that eligible clinicians who do not meet the threshold, but who are providing high-value care as defined by the QPP, are “forced to leave higher reimbursement rates on the table; these could be considerable over time.”
In addition, AMGA said that expanding the exemption decreases the money available for those who are required to participate. The CMS estimates in the proposed rule that in payment year 2019, $1.333 billion would be paid to top performers (including $500 million in exceptional performance bonus payments), but under the newest proposal, that number drops to $673 million (including $500 million in exceptional performance bonus payments). This will translate to a 0.3% bump in payment in 2020.
“The effect of eliminating of two-thirds of eligible clinicians from the MIPS formula is to financially undermine participating clinicians,” AMGA said in comments to the CMS. “They effectively lose by winning.”
Funding for Treatment Drug Courts
The Substance Abuse and Mental Health Services Administration (SAMHSA) has announced $80.8 million in grants to treatment drug court programs for people with substance use and mental disorders. “Treatment drug courts improve health and recovery outcomes, reduce the burden on the criminal justice system, and help people recover in their communities,” said Kim Johnson, PhD, director for the Center for Substance Abuse Treatment.
Related: California Opens Treatment Center for Native Youth
The grant programs include $17.8 million per year for up to 3 years to 44 existing Adult Treatment Drug courts and adult Tribal Healing to Wellness courts, which use the treatment drug court model to provide alcohol and drug treatment.
Related: IHS Funds Programs to Protect Native Youth from Substance Abuse
Another $8.2 million per year for up to 5 years will go to 20 programs to expand or enhance substance use disorder treatment services in family treatment drug courts.
The Substance Abuse and Mental Health Services Administration (SAMHSA) has announced $80.8 million in grants to treatment drug court programs for people with substance use and mental disorders. “Treatment drug courts improve health and recovery outcomes, reduce the burden on the criminal justice system, and help people recover in their communities,” said Kim Johnson, PhD, director for the Center for Substance Abuse Treatment.
Related: California Opens Treatment Center for Native Youth
The grant programs include $17.8 million per year for up to 3 years to 44 existing Adult Treatment Drug courts and adult Tribal Healing to Wellness courts, which use the treatment drug court model to provide alcohol and drug treatment.
Related: IHS Funds Programs to Protect Native Youth from Substance Abuse
Another $8.2 million per year for up to 5 years will go to 20 programs to expand or enhance substance use disorder treatment services in family treatment drug courts.
The Substance Abuse and Mental Health Services Administration (SAMHSA) has announced $80.8 million in grants to treatment drug court programs for people with substance use and mental disorders. “Treatment drug courts improve health and recovery outcomes, reduce the burden on the criminal justice system, and help people recover in their communities,” said Kim Johnson, PhD, director for the Center for Substance Abuse Treatment.
Related: California Opens Treatment Center for Native Youth
The grant programs include $17.8 million per year for up to 3 years to 44 existing Adult Treatment Drug courts and adult Tribal Healing to Wellness courts, which use the treatment drug court model to provide alcohol and drug treatment.
Related: IHS Funds Programs to Protect Native Youth from Substance Abuse
Another $8.2 million per year for up to 5 years will go to 20 programs to expand or enhance substance use disorder treatment services in family treatment drug courts.
Maintenance will be a new standard in MCL, doc says
Results of a phase 3 trial suggest rituximab maintenance after transplant can prolong survival in non-elderly patients with mantle cell lymphoma (MCL).
Compared to patients who did not receive maintenance, those who received rituximab every other month for 3 years after autologous transplant had superior event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).
Researchers reported these results in NEJM. The study was funded by Roche and Amgen.
“We demonstrate, with this study, that treatment with immunotherapy can delay the onset of relapse and prolong the survival of patients,” said study author Steven Le Gouill, MD, PhD, of CHU de Nantes in France.*
“It is clear that the use of rituximab maintenance after chemotherapy in this type of lymphoma will become a new standard of treatment.”
Dr Le Gouill and his colleagues began this study with 299 MCL patients. Their median age was 57 (range, 27-65), and 79% were male. Most had Ann Arbor stage IV disease (84%), followed by III (10%), and II (6%).
According to MIPI, 53% of patients had low-risk disease, 27% had intermediate-risk MCL, and 19% had high-risk disease. Ninety-four percent of patients had an ECOG performance status score below 3.
Treatment
Patients first received 4 courses of induction with R-DHAP (rituximab, dexamethasone, cytarabine, and a platinum derivative [carboplatin, oxaliplatin, or cisplatin]).
The overall response rate was 94%, with 41% (n=124) achieving a complete response (CR) and 36% (n=107) achieving an unconfirmed CR.
Twenty patients who had an insufficient response then received 4 courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Eleven of these patients went on to receive an autologous hematopoietic stem cell transplant (HSCT).
In all, 257 patients (86%) underwent autologous HSCT. The conditioning regimen was R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan).
Sixty-five percent of patients (n=168) achieved a CR after HSCT, and 24% (n=61) had an unconfirmed CR.
Up to 3 months after HSCT, patients were randomized to observation (n=120) or to receive rituximab (375 mg/m2) every 2 months for 3 years (n=120).
The researchers said there were no significant differences between these 2 groups regarding characteristics at study enrollment or the patients’ disease status at randomization.
Results
The median follow-up from randomization was 50.2 months (range, 46.4 to 54.2). The median EFS, PFS, and OS were not reached in either group.
The 4-year EFS was 79% in the rituximab group and 61% in the observation group (P=0.001). The 4-year PFS was 83% and 64%, respectively (P<0.001). And the 4-year OS was 89% and 80%, respectively (P=0.04).
Of the 11 patients who received R-CHOP before randomization, 4 were randomized to the rituximab group and 7 to the observation group.
One patient in the rituximab group relapsed and died. The other 3 were still alive and disease-free at the final analysis.
In the observation group, 4 patients had relapsed but were alive as of the final analysis, while 3 patients had died.
There were 59 patients who did not undergo randomization (due to disease progression, death, HSCT ineligibility, toxic effects, and other reasons).
For these patients, the median PFS was 11.0 months, and the median OS was 30.6 months. 
*Quote has been translated from French.
Results of a phase 3 trial suggest rituximab maintenance after transplant can prolong survival in non-elderly patients with mantle cell lymphoma (MCL).
Compared to patients who did not receive maintenance, those who received rituximab every other month for 3 years after autologous transplant had superior event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).
Researchers reported these results in NEJM. The study was funded by Roche and Amgen.
“We demonstrate, with this study, that treatment with immunotherapy can delay the onset of relapse and prolong the survival of patients,” said study author Steven Le Gouill, MD, PhD, of CHU de Nantes in France.*
“It is clear that the use of rituximab maintenance after chemotherapy in this type of lymphoma will become a new standard of treatment.”
Dr Le Gouill and his colleagues began this study with 299 MCL patients. Their median age was 57 (range, 27-65), and 79% were male. Most had Ann Arbor stage IV disease (84%), followed by III (10%), and II (6%).
According to MIPI, 53% of patients had low-risk disease, 27% had intermediate-risk MCL, and 19% had high-risk disease. Ninety-four percent of patients had an ECOG performance status score below 3.
Treatment
Patients first received 4 courses of induction with R-DHAP (rituximab, dexamethasone, cytarabine, and a platinum derivative [carboplatin, oxaliplatin, or cisplatin]).
The overall response rate was 94%, with 41% (n=124) achieving a complete response (CR) and 36% (n=107) achieving an unconfirmed CR.
Twenty patients who had an insufficient response then received 4 courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Eleven of these patients went on to receive an autologous hematopoietic stem cell transplant (HSCT).
In all, 257 patients (86%) underwent autologous HSCT. The conditioning regimen was R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan).
Sixty-five percent of patients (n=168) achieved a CR after HSCT, and 24% (n=61) had an unconfirmed CR.
Up to 3 months after HSCT, patients were randomized to observation (n=120) or to receive rituximab (375 mg/m2) every 2 months for 3 years (n=120).
The researchers said there were no significant differences between these 2 groups regarding characteristics at study enrollment or the patients’ disease status at randomization.
Results
The median follow-up from randomization was 50.2 months (range, 46.4 to 54.2). The median EFS, PFS, and OS were not reached in either group.
The 4-year EFS was 79% in the rituximab group and 61% in the observation group (P=0.001). The 4-year PFS was 83% and 64%, respectively (P<0.001). And the 4-year OS was 89% and 80%, respectively (P=0.04).
Of the 11 patients who received R-CHOP before randomization, 4 were randomized to the rituximab group and 7 to the observation group.
One patient in the rituximab group relapsed and died. The other 3 were still alive and disease-free at the final analysis.
In the observation group, 4 patients had relapsed but were alive as of the final analysis, while 3 patients had died.
There were 59 patients who did not undergo randomization (due to disease progression, death, HSCT ineligibility, toxic effects, and other reasons).
For these patients, the median PFS was 11.0 months, and the median OS was 30.6 months.
*Quote has been translated from French.
Results of a phase 3 trial suggest rituximab maintenance after transplant can prolong survival in non-elderly patients with mantle cell lymphoma (MCL).
Compared to patients who did not receive maintenance, those who received rituximab every other month for 3 years after autologous transplant had superior event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).
Researchers reported these results in NEJM. The study was funded by Roche and Amgen.
“We demonstrate, with this study, that treatment with immunotherapy can delay the onset of relapse and prolong the survival of patients,” said study author Steven Le Gouill, MD, PhD, of CHU de Nantes in France.*
“It is clear that the use of rituximab maintenance after chemotherapy in this type of lymphoma will become a new standard of treatment.”
Dr Le Gouill and his colleagues began this study with 299 MCL patients. Their median age was 57 (range, 27-65), and 79% were male. Most had Ann Arbor stage IV disease (84%), followed by III (10%), and II (6%).
According to MIPI, 53% of patients had low-risk disease, 27% had intermediate-risk MCL, and 19% had high-risk disease. Ninety-four percent of patients had an ECOG performance status score below 3.
Treatment
Patients first received 4 courses of induction with R-DHAP (rituximab, dexamethasone, cytarabine, and a platinum derivative [carboplatin, oxaliplatin, or cisplatin]).
The overall response rate was 94%, with 41% (n=124) achieving a complete response (CR) and 36% (n=107) achieving an unconfirmed CR.
Twenty patients who had an insufficient response then received 4 courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Eleven of these patients went on to receive an autologous hematopoietic stem cell transplant (HSCT).
In all, 257 patients (86%) underwent autologous HSCT. The conditioning regimen was R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan).
Sixty-five percent of patients (n=168) achieved a CR after HSCT, and 24% (n=61) had an unconfirmed CR.
Up to 3 months after HSCT, patients were randomized to observation (n=120) or to receive rituximab (375 mg/m2) every 2 months for 3 years (n=120).
The researchers said there were no significant differences between these 2 groups regarding characteristics at study enrollment or the patients’ disease status at randomization.
Results
The median follow-up from randomization was 50.2 months (range, 46.4 to 54.2). The median EFS, PFS, and OS were not reached in either group.
The 4-year EFS was 79% in the rituximab group and 61% in the observation group (P=0.001). The 4-year PFS was 83% and 64%, respectively (P<0.001). And the 4-year OS was 89% and 80%, respectively (P=0.04).
Of the 11 patients who received R-CHOP before randomization, 4 were randomized to the rituximab group and 7 to the observation group.
One patient in the rituximab group relapsed and died. The other 3 were still alive and disease-free at the final analysis.
In the observation group, 4 patients had relapsed but were alive as of the final analysis, while 3 patients had died.
There were 59 patients who did not undergo randomization (due to disease progression, death, HSCT ineligibility, toxic effects, and other reasons).
For these patients, the median PFS was 11.0 months, and the median OS was 30.6 months.
*Quote has been translated from French.
Drugs could improve treatment of CML
Preclinical research suggests 2 drugs already approved for use in the US may improve upon tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML).
The drugs are prostaglandin E1 (PGE1), which is used to treat erectile dysfunction, and misoprostol, which is used to prevent stomach ulcers.
Researchers found that each of these drugs could suppress leukemic stem cells (LSCs) and enhance the activity of imatinib in mice with CML.
Hai-Hui (Howard) Xue, MD, PhD, of University of Iowa in Iowa City, and his colleagues reported these findings in Cell Stem Cell.
“A successful treatment [for CML] is expected to kill the bulk leukemia cells and, at the same time, get rid of the leukemic stem cells,” Dr Xue said. “Potentially, that could lead to a cure.”
Therefore, Dr Xue and his colleagues set out to find drugs that could eradicate LSCs.
The researchers had previously shown that CML LSCs are “strongly dependent” on 2 transcription factors—Tcf1 and Lef1—for self-renewal, whereas normal hematopoietic stem and progenitor cells are not.
With their current research, the team found that Tcf1/Lef1 deficiency “at least partly impairs the transcriptional program” that maintains LSCs in mice and humans with CML.
So the researchers used connectivity maps to identify molecules that could replicate Tcf1/Lef1 deficiency. This screen revealed PGE1.
The team found that PGE1 inhibited the activity and self-renewal of CML LSCs. And the combination of PGE1 and imatinib could reduce leukemia growth in mouse models of CML.
When the mice received no treatment or imatinib alone, LSCs persisted. However, PGE1 enhanced the efficacy of imatinib, and mice that received this combination saw their LSCs “greatly diminished.”
The researchers then transplanted LSCs from these mice into secondary hosts and monitored their survival without administering additional treatment.
Mice that received PGE1-pretreated LSCs lived significantly longer (P<0.001) than mice that received imatinib-pretreated LSCs. And mice that received LSCs pretreated with PGE1 and imatinib lived significantly longer than mice that received PGE1-pretreated LSCs (P=0.039).
Investigating how PGE1 works to suppress LSCs, the researchers found the effect relies on a critical interaction between PGE1 and its receptor, EP4.
So the team tested misoprostol, which also interacts with EP4, in mice with CML.
The researchers found that misoprostol alone diminished LSCs, and the combination of misoprostol and imatinib “exhibited stronger effects.”
In addition, mice that received LSCs from animals previously treated with misoprostol survived longer and had a reduction in leukemia burden compared to mice that received untreated LSCs.
“We would like to be able to test these compounds in a clinical trial,” Dr Xue said. “If we could show that the combination of TKI with PGE1 or misoprostol can eliminate both the bulk tumor cells and the stem cells that keep the tumor going, that could potentially eliminate the cancer to the point where a patient would no longer need to depend on TKI.”
Preclinical research suggests 2 drugs already approved for use in the US may improve upon tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML).
The drugs are prostaglandin E1 (PGE1), which is used to treat erectile dysfunction, and misoprostol, which is used to prevent stomach ulcers.
Researchers found that each of these drugs could suppress leukemic stem cells (LSCs) and enhance the activity of imatinib in mice with CML.
Hai-Hui (Howard) Xue, MD, PhD, of University of Iowa in Iowa City, and his colleagues reported these findings in Cell Stem Cell.
“A successful treatment [for CML] is expected to kill the bulk leukemia cells and, at the same time, get rid of the leukemic stem cells,” Dr Xue said. “Potentially, that could lead to a cure.”
Therefore, Dr Xue and his colleagues set out to find drugs that could eradicate LSCs.
The researchers had previously shown that CML LSCs are “strongly dependent” on 2 transcription factors—Tcf1 and Lef1—for self-renewal, whereas normal hematopoietic stem and progenitor cells are not.
With their current research, the team found that Tcf1/Lef1 deficiency “at least partly impairs the transcriptional program” that maintains LSCs in mice and humans with CML.
So the researchers used connectivity maps to identify molecules that could replicate Tcf1/Lef1 deficiency. This screen revealed PGE1.
The team found that PGE1 inhibited the activity and self-renewal of CML LSCs. And the combination of PGE1 and imatinib could reduce leukemia growth in mouse models of CML.
When the mice received no treatment or imatinib alone, LSCs persisted. However, PGE1 enhanced the efficacy of imatinib, and mice that received this combination saw their LSCs “greatly diminished.”
The researchers then transplanted LSCs from these mice into secondary hosts and monitored their survival without administering additional treatment.
Mice that received PGE1-pretreated LSCs lived significantly longer (P<0.001) than mice that received imatinib-pretreated LSCs. And mice that received LSCs pretreated with PGE1 and imatinib lived significantly longer than mice that received PGE1-pretreated LSCs (P=0.039).
Investigating how PGE1 works to suppress LSCs, the researchers found the effect relies on a critical interaction between PGE1 and its receptor, EP4.
So the team tested misoprostol, which also interacts with EP4, in mice with CML.
The researchers found that misoprostol alone diminished LSCs, and the combination of misoprostol and imatinib “exhibited stronger effects.”
In addition, mice that received LSCs from animals previously treated with misoprostol survived longer and had a reduction in leukemia burden compared to mice that received untreated LSCs.
“We would like to be able to test these compounds in a clinical trial,” Dr Xue said. “If we could show that the combination of TKI with PGE1 or misoprostol can eliminate both the bulk tumor cells and the stem cells that keep the tumor going, that could potentially eliminate the cancer to the point where a patient would no longer need to depend on TKI.”
Preclinical research suggests 2 drugs already approved for use in the US may improve upon tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML).
The drugs are prostaglandin E1 (PGE1), which is used to treat erectile dysfunction, and misoprostol, which is used to prevent stomach ulcers.
Researchers found that each of these drugs could suppress leukemic stem cells (LSCs) and enhance the activity of imatinib in mice with CML.
Hai-Hui (Howard) Xue, MD, PhD, of University of Iowa in Iowa City, and his colleagues reported these findings in Cell Stem Cell.
“A successful treatment [for CML] is expected to kill the bulk leukemia cells and, at the same time, get rid of the leukemic stem cells,” Dr Xue said. “Potentially, that could lead to a cure.”
Therefore, Dr Xue and his colleagues set out to find drugs that could eradicate LSCs.
The researchers had previously shown that CML LSCs are “strongly dependent” on 2 transcription factors—Tcf1 and Lef1—for self-renewal, whereas normal hematopoietic stem and progenitor cells are not.
With their current research, the team found that Tcf1/Lef1 deficiency “at least partly impairs the transcriptional program” that maintains LSCs in mice and humans with CML.
So the researchers used connectivity maps to identify molecules that could replicate Tcf1/Lef1 deficiency. This screen revealed PGE1.
The team found that PGE1 inhibited the activity and self-renewal of CML LSCs. And the combination of PGE1 and imatinib could reduce leukemia growth in mouse models of CML.
When the mice received no treatment or imatinib alone, LSCs persisted. However, PGE1 enhanced the efficacy of imatinib, and mice that received this combination saw their LSCs “greatly diminished.”
The researchers then transplanted LSCs from these mice into secondary hosts and monitored their survival without administering additional treatment.
Mice that received PGE1-pretreated LSCs lived significantly longer (P<0.001) than mice that received imatinib-pretreated LSCs. And mice that received LSCs pretreated with PGE1 and imatinib lived significantly longer than mice that received PGE1-pretreated LSCs (P=0.039).
Investigating how PGE1 works to suppress LSCs, the researchers found the effect relies on a critical interaction between PGE1 and its receptor, EP4.
So the team tested misoprostol, which also interacts with EP4, in mice with CML.
The researchers found that misoprostol alone diminished LSCs, and the combination of misoprostol and imatinib “exhibited stronger effects.”
In addition, mice that received LSCs from animals previously treated with misoprostol survived longer and had a reduction in leukemia burden compared to mice that received untreated LSCs.
“We would like to be able to test these compounds in a clinical trial,” Dr Xue said. “If we could show that the combination of TKI with PGE1 or misoprostol can eliminate both the bulk tumor cells and the stem cells that keep the tumor going, that could potentially eliminate the cancer to the point where a patient would no longer need to depend on TKI.”
FDA improves public access to AE data
The US Food and Drug Administration (FDA) has launched a new search tool designed to improve access to data in the FDA’s Adverse Event Reporting System (FAERS).
FAERS includes data on adverse events (AEs) associated with drug and biologic products.
The new FAERs public dashboard allows users to search for and organize data by criteria such as drug/biological product, age of the patient, type of AE, year the AE occurred, or within a specific time frame.
The FDA intends for this tool to increase transparency by making it easier for people to see reports the agency receives.
The FDA hopes this, in turn, will spur the submission of more detailed and complete reports from consumers, healthcare professionals, and others.
The FDA uses FAERS for surveillance, such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer’s compliance with reporting regulations, and responding to outside requests for information.
The reports in FAERS are evaluated by clinical reviewers in the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to monitor the safety of products after they are marketed. If a potential safety concern is identified in FAERS, further evaluation is performed.
“Our focus on safety extends beyond approval,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.
“In fact, our staff spends a lot of time looking at FAERS reports received regarding approved drug and biologic products, and these reports can be very valuable components of our safety assessments. By giving people a better understanding of these data, and the associated limitations, we hope the new interface will encourage people to submit more complete reports.”
The FDA encourages healthcare professionals and consumers to report AEs or quality problems related to drugs and biologics to the FDA’s MedWatch Adverse Event Reporting Program.
In addition to the FAERS database for drugs and biologics, the FDA has AE reporting programs and databases for foods, dietary supplements, and cosmetics (CFSAN Adverse Event Reporting System [CAERS]), medical devices (Manufacturer and User Facility Device Experience [MAUDE]), and vaccines (Vaccine Adverse Event Reporting System [VAERS], which the FDA co-manages with the Centers for Disease Control and Prevention).
The US Food and Drug Administration (FDA) has launched a new search tool designed to improve access to data in the FDA’s Adverse Event Reporting System (FAERS).
FAERS includes data on adverse events (AEs) associated with drug and biologic products.
The new FAERs public dashboard allows users to search for and organize data by criteria such as drug/biological product, age of the patient, type of AE, year the AE occurred, or within a specific time frame.
The FDA intends for this tool to increase transparency by making it easier for people to see reports the agency receives.
The FDA hopes this, in turn, will spur the submission of more detailed and complete reports from consumers, healthcare professionals, and others.
The FDA uses FAERS for surveillance, such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer’s compliance with reporting regulations, and responding to outside requests for information.
The reports in FAERS are evaluated by clinical reviewers in the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to monitor the safety of products after they are marketed. If a potential safety concern is identified in FAERS, further evaluation is performed.
“Our focus on safety extends beyond approval,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.
“In fact, our staff spends a lot of time looking at FAERS reports received regarding approved drug and biologic products, and these reports can be very valuable components of our safety assessments. By giving people a better understanding of these data, and the associated limitations, we hope the new interface will encourage people to submit more complete reports.”
The FDA encourages healthcare professionals and consumers to report AEs or quality problems related to drugs and biologics to the FDA’s MedWatch Adverse Event Reporting Program.
In addition to the FAERS database for drugs and biologics, the FDA has AE reporting programs and databases for foods, dietary supplements, and cosmetics (CFSAN Adverse Event Reporting System [CAERS]), medical devices (Manufacturer and User Facility Device Experience [MAUDE]), and vaccines (Vaccine Adverse Event Reporting System [VAERS], which the FDA co-manages with the Centers for Disease Control and Prevention).
The US Food and Drug Administration (FDA) has launched a new search tool designed to improve access to data in the FDA’s Adverse Event Reporting System (FAERS).
FAERS includes data on adverse events (AEs) associated with drug and biologic products.
The new FAERs public dashboard allows users to search for and organize data by criteria such as drug/biological product, age of the patient, type of AE, year the AE occurred, or within a specific time frame.
The FDA intends for this tool to increase transparency by making it easier for people to see reports the agency receives.
The FDA hopes this, in turn, will spur the submission of more detailed and complete reports from consumers, healthcare professionals, and others.
The FDA uses FAERS for surveillance, such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer’s compliance with reporting regulations, and responding to outside requests for information.
The reports in FAERS are evaluated by clinical reviewers in the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to monitor the safety of products after they are marketed. If a potential safety concern is identified in FAERS, further evaluation is performed.
“Our focus on safety extends beyond approval,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.
“In fact, our staff spends a lot of time looking at FAERS reports received regarding approved drug and biologic products, and these reports can be very valuable components of our safety assessments. By giving people a better understanding of these data, and the associated limitations, we hope the new interface will encourage people to submit more complete reports.”
The FDA encourages healthcare professionals and consumers to report AEs or quality problems related to drugs and biologics to the FDA’s MedWatch Adverse Event Reporting Program.
In addition to the FAERS database for drugs and biologics, the FDA has AE reporting programs and databases for foods, dietary supplements, and cosmetics (CFSAN Adverse Event Reporting System [CAERS]), medical devices (Manufacturer and User Facility Device Experience [MAUDE]), and vaccines (Vaccine Adverse Event Reporting System [VAERS], which the FDA co-manages with the Centers for Disease Control and Prevention).
Anticoagulation for patients with liver cirrhosis and portal vein thrombosis
Clinical question: Should patients with liver cirrhosis with portal vein thrombosis be treated with anticoagulation?
Background: Portal vein thrombosis occurs in about 20% of patients with liver cirrhosis. Previously these patients were not often treated with anticoagulation due to concern for increased bleeding risk associated with advanced liver disease. However, restoring portal vein patency may prevent further sequelae, including intestinal infarction and portal hypertension and may also affect candidacy for liver transplantation.
Setting: Multiple sites throughout the world.
Synopsis: The authors of this meta-analysis pooled data from eight clinical trials, comprising 353 patients with liver cirrhosis and portal vein thrombosis, to assess the rates of complete and partial recanalization with anticoagulation therapy (warfarin or low molecular weight heparin) versus no therapy. The authors also assessed the rate of minor and major bleeding complications in patients who received anticoagulation, compared with those who received no therapy. Patients who received anticoagulation therapy had increased recanalization and reduced progression of thrombosis without excessive major and minor bleeding.
Bottom line: This meta-analysis suggests anticoagulation might be safe and effective in treating portal vein thrombosis in patients with cirrhosis; however, this analysis was based on nonrandomized clinical trials and did not address long-term important endpoints, such as the effect of anticoagulation on mortality.
Citation: Loffredo L, Pastori D, Farcomeni A, Violi F. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: A systematic review and meta-analysis. Gastroenterology. 2017 May 4. E-published ahead of print.
Dr. Teixeira is a hospitalist at Ochsner Health System, New Orleans.
Clinical question: Should patients with liver cirrhosis with portal vein thrombosis be treated with anticoagulation?
Background: Portal vein thrombosis occurs in about 20% of patients with liver cirrhosis. Previously these patients were not often treated with anticoagulation due to concern for increased bleeding risk associated with advanced liver disease. However, restoring portal vein patency may prevent further sequelae, including intestinal infarction and portal hypertension and may also affect candidacy for liver transplantation.
Setting: Multiple sites throughout the world.
Synopsis: The authors of this meta-analysis pooled data from eight clinical trials, comprising 353 patients with liver cirrhosis and portal vein thrombosis, to assess the rates of complete and partial recanalization with anticoagulation therapy (warfarin or low molecular weight heparin) versus no therapy. The authors also assessed the rate of minor and major bleeding complications in patients who received anticoagulation, compared with those who received no therapy. Patients who received anticoagulation therapy had increased recanalization and reduced progression of thrombosis without excessive major and minor bleeding.
Bottom line: This meta-analysis suggests anticoagulation might be safe and effective in treating portal vein thrombosis in patients with cirrhosis; however, this analysis was based on nonrandomized clinical trials and did not address long-term important endpoints, such as the effect of anticoagulation on mortality.
Citation: Loffredo L, Pastori D, Farcomeni A, Violi F. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: A systematic review and meta-analysis. Gastroenterology. 2017 May 4. E-published ahead of print.
Dr. Teixeira is a hospitalist at Ochsner Health System, New Orleans.
Clinical question: Should patients with liver cirrhosis with portal vein thrombosis be treated with anticoagulation?
Background: Portal vein thrombosis occurs in about 20% of patients with liver cirrhosis. Previously these patients were not often treated with anticoagulation due to concern for increased bleeding risk associated with advanced liver disease. However, restoring portal vein patency may prevent further sequelae, including intestinal infarction and portal hypertension and may also affect candidacy for liver transplantation.
Setting: Multiple sites throughout the world.
Synopsis: The authors of this meta-analysis pooled data from eight clinical trials, comprising 353 patients with liver cirrhosis and portal vein thrombosis, to assess the rates of complete and partial recanalization with anticoagulation therapy (warfarin or low molecular weight heparin) versus no therapy. The authors also assessed the rate of minor and major bleeding complications in patients who received anticoagulation, compared with those who received no therapy. Patients who received anticoagulation therapy had increased recanalization and reduced progression of thrombosis without excessive major and minor bleeding.
Bottom line: This meta-analysis suggests anticoagulation might be safe and effective in treating portal vein thrombosis in patients with cirrhosis; however, this analysis was based on nonrandomized clinical trials and did not address long-term important endpoints, such as the effect of anticoagulation on mortality.
Citation: Loffredo L, Pastori D, Farcomeni A, Violi F. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: A systematic review and meta-analysis. Gastroenterology. 2017 May 4. E-published ahead of print.
Dr. Teixeira is a hospitalist at Ochsner Health System, New Orleans.