Mixed Topics

On car trips with our kids, we used to listen to comedy tapes. (Cassette tapes. Look them up.) One of our favorite comics was Steven Wright, who made it to the Tonight Show with Johnny Carson. (Google him.)

Wright’s offbeat humor was quirky and a bit philosophical, and was delivered in a deadpan, mumbled monotone. For instance:

When I got to school, the teacher said, “The socks you’re wearing don’t match. They’re two different colors.”

I said, “I go by thickness.”

That punchline goes pop in your head, like a shy little firecracker: How come it never occurred to me to look at it that way?

I thought of Steven Wright recently while I was enrolling Stacy, a 20-year-old, in the iPledge program for a planned course of isotretinoin. Stacy told me she is sexually active and has an IUD.

“When you start the medicine next month,” I told her, “you’ll need to pick a second form of contraception.”

Stacy looked bewildered. When I’ve made that statement to a thousand previous patients, none of them ever looked bewildered.

“I mean,” I said, “besides the IUD, you’ll need to use a second type of contraception, to be sure you don’t get pregnant. You could choose condoms, or one of the other types listed in the booklet I gave you.”

That didn’t seem to help. Stacey hemmed a bit. “Does that mean I have to tell you ... ?”

“Yes, you have to pick another form of birth control and tell me which one it is.”

“I have to tell you every time?”

My go-by-thickness moment – I finally got it. “NO,” I said. “You do NOT have to tell me which second contraceptive you use every time you have sex!”

Steven Wright would be proud of Stacy. Isotretinoin came out in 1982, but nobody ever thought of “choose a second type of contraception” that way before. Stacy goes by retail.

That case reminded of another out-of-left field question I heard for the first – and only – time almost 40 years ago. I had prescribed a cream for a young man.

“Can I get it refilled?” he asked.

“Sure,” I said.

“How do I refill it?” he asked.

“You take it back to the pharmacy, and they refill it for you,” I said.

“But how do they refill it?”

“You show them what you need, and they refill it.”

“But how?”

“Why do you keep asking me that?”

“The tube is going to be all scrunched up from my squeezing it,” he said. “How do they get the new cream back in?”

Well son of a gun, “refill” could mean that, couldn’t it? If you go by thickness.

In idle moments I like to let novel perspectives such as those roll around in my head. The other day I accompanied a relative to an emergency department. While waiting in triage for 5 hours, I looked up and saw a sign on the wall, in big, blue letters: “Support ED Research!”

That puzzled me. I know it can be an important problem, but why the dickens would someone come to an emergency department for erectile dysfunction?

I go by acronyms.
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

On car trips with our kids, we used to listen to comedy tapes. (Cassette tapes. Look them up.) One of our favorite comics was Steven Wright, who made it to the Tonight Show with Johnny Carson. (Google him.)

Wright’s offbeat humor was quirky and a bit philosophical, and was delivered in a deadpan, mumbled monotone. For instance:

When I got to school, the teacher said, “The socks you’re wearing don’t match. They’re two different colors.”

I said, “I go by thickness.”

That punchline goes pop in your head, like a shy little firecracker: How come it never occurred to me to look at it that way?

I thought of Steven Wright recently while I was enrolling Stacy, a 20-year-old, in the iPledge program for a planned course of isotretinoin. Stacy told me she is sexually active and has an IUD.

“When you start the medicine next month,” I told her, “you’ll need to pick a second form of contraception.”

Stacy looked bewildered. When I’ve made that statement to a thousand previous patients, none of them ever looked bewildered.

“I mean,” I said, “besides the IUD, you’ll need to use a second type of contraception, to be sure you don’t get pregnant. You could choose condoms, or one of the other types listed in the booklet I gave you.”

That didn’t seem to help. Stacey hemmed a bit. “Does that mean I have to tell you ... ?”

“Yes, you have to pick another form of birth control and tell me which one it is.”

“I have to tell you every time?”

My go-by-thickness moment – I finally got it. “NO,” I said. “You do NOT have to tell me which second contraceptive you use every time you have sex!”

Steven Wright would be proud of Stacy. Isotretinoin came out in 1982, but nobody ever thought of “choose a second type of contraception” that way before. Stacy goes by retail.

That case reminded of another out-of-left field question I heard for the first – and only – time almost 40 years ago. I had prescribed a cream for a young man.

“Can I get it refilled?” he asked.

“Sure,” I said.

“How do I refill it?” he asked.

“You take it back to the pharmacy, and they refill it for you,” I said.

“But how do they refill it?”

“You show them what you need, and they refill it.”

“But how?”

“Why do you keep asking me that?”

“The tube is going to be all scrunched up from my squeezing it,” he said. “How do they get the new cream back in?”

Well son of a gun, “refill” could mean that, couldn’t it? If you go by thickness.

In idle moments I like to let novel perspectives such as those roll around in my head. The other day I accompanied a relative to an emergency department. While waiting in triage for 5 hours, I looked up and saw a sign on the wall, in big, blue letters: “Support ED Research!”

That puzzled me. I know it can be an important problem, but why the dickens would someone come to an emergency department for erectile dysfunction?

I go by acronyms.
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

On car trips with our kids, we used to listen to comedy tapes. (Cassette tapes. Look them up.) One of our favorite comics was Steven Wright, who made it to the Tonight Show with Johnny Carson. (Google him.)

Wright’s offbeat humor was quirky and a bit philosophical, and was delivered in a deadpan, mumbled monotone. For instance:

When I got to school, the teacher said, “The socks you’re wearing don’t match. They’re two different colors.”

I said, “I go by thickness.”

That punchline goes pop in your head, like a shy little firecracker: How come it never occurred to me to look at it that way?

I thought of Steven Wright recently while I was enrolling Stacy, a 20-year-old, in the iPledge program for a planned course of isotretinoin. Stacy told me she is sexually active and has an IUD.

“When you start the medicine next month,” I told her, “you’ll need to pick a second form of contraception.”

Stacy looked bewildered. When I’ve made that statement to a thousand previous patients, none of them ever looked bewildered.

“I mean,” I said, “besides the IUD, you’ll need to use a second type of contraception, to be sure you don’t get pregnant. You could choose condoms, or one of the other types listed in the booklet I gave you.”

That didn’t seem to help. Stacey hemmed a bit. “Does that mean I have to tell you ... ?”

“Yes, you have to pick another form of birth control and tell me which one it is.”

“I have to tell you every time?”

My go-by-thickness moment – I finally got it. “NO,” I said. “You do NOT have to tell me which second contraceptive you use every time you have sex!”

Steven Wright would be proud of Stacy. Isotretinoin came out in 1982, but nobody ever thought of “choose a second type of contraception” that way before. Stacy goes by retail.

That case reminded of another out-of-left field question I heard for the first – and only – time almost 40 years ago. I had prescribed a cream for a young man.

“Can I get it refilled?” he asked.

“Sure,” I said.

“How do I refill it?” he asked.

“You take it back to the pharmacy, and they refill it for you,” I said.

“But how do they refill it?”

“You show them what you need, and they refill it.”

“But how?”

“Why do you keep asking me that?”

“The tube is going to be all scrunched up from my squeezing it,” he said. “How do they get the new cream back in?”

Well son of a gun, “refill” could mean that, couldn’t it? If you go by thickness.

In idle moments I like to let novel perspectives such as those roll around in my head. The other day I accompanied a relative to an emergency department. While waiting in triage for 5 hours, I looked up and saw a sign on the wall, in big, blue letters: “Support ED Research!”

That puzzled me. I know it can be an important problem, but why the dickens would someone come to an emergency department for erectile dysfunction?

I go by acronyms.
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

On the big stage at HM19 in late March, Carrie Herzke, MD, FAAP, FACP, SFHM, and Christopher Moriates, MD, FACP, SFHM, undertook the daunting task of summarizing a year’s worth of research relevant to the practice of hospital medicine – all within the span of an hour.

As has been standard with the “Update in Hospital Medicine” session at previous SHM Annual Conferences, the presenters touched on lighter topics in the medical literature: a prospective cohort study that found drinking coffee was inversely associated with mortality, even for those who drink up to eight cups a day; a cross-sectional observational study in which patients noted that what a physician wears is an important consideration for them during care, with a white coat preferred over formal attire as the most highly rated preference in a clinical care setting; and a study from a pediatric journal in which researchers calculated the average transit time for a Lego figurine head ingested by an adult.

But Dr. Herzke and Dr. Moriates mainly covered more serious subjects. In an interview before the session, Dr. Herzke, associate vice chair for clinical affairs in the department of medicine at Johns Hopkins Medicine in Baltimore, said she and Dr. Moriates chose studies across the fields of infectious diseases, cardiology, and hematology that should make hospitalists question common practices and consider changing how they practice medicine at their home institution.

Dr. Moriates, assistant dean for health care value at the University of Texas at Austin, said in an interview that their topic choices reflected the breadth and diversity of patients taken care of by hospitalists.

For example, he noted during the HM19 session that results from several studies suggest hospitalists may soon choose oral antibiotics over IV antibiotics for care of certain patient populations: the recent POET trial suggests use of oral antibiotics for patients with left-sided infective endocarditis resulted in a lower length of stay in hospital (19 inpatient days) when compared with use of IV antibiotics (3 inpatient days and 17 additional treatment days post discharge), while the OVIVA trial found a lower but noninferior treatment failure rate among patients who received oral antibiotics for bone and joint infection, compared with IV antibiotics. Although these were both well-done studies, Dr. Moriates and Dr. Herzke emphasized that the results challenge widely accepted standards of care, and it may not yet be time for a paradigm shift.

Direct oral anticoagulants (DOACs) also are being studied in patients with end-stage renal disease (ESRD) and cancer, Dr. Herzke said, and apixaban (Eliquis) 5 mg appears to be the preferred dose for a lower risk of stroke and mortality in patients with ESRD and atrial fibrillation. The speakers said there are further studies being developed for management of AF in patients with heart failure and DOACs for patients with ESRD.

Another retrospective cohort study from research in the Massachusetts Public Health Dataset found that buprenorphine may have a number needed to treat of 50 for opioid use disorder, which Dr. Moriates said is close in proximity for the number needed to treat for aspirin. “It seems like it’s time for this to become standard of care,” he said.

The speakers also highlighted common practices hospitalists should stop performing based on the latest evidence.

In one example, they revealed that there is conflicting research on angiotensin-converting enzyme (ACE) inhibitors. One study found transient preoperative interruption of ACE inhibitors was associated with a reduction in intraoperative hypotension during a noncardiac, nonvascular surgery. A second study linked ACE inhibitor use with a reduction in all-cause mortality. However, long-term use of ACE inhibitors also appears to be associated with a 14% increase in lung cancers, with an increased incidence based on longer use duration.

Hospitalists should also be aware of recommendations from a study on oxygen therapy, Dr. Herzke noted, which found that extra oxygen therapy may harm patients with MI or stroke; as a result, hospitalists should “wean oxygen as tolerated” in these patients. In addition, hospitalists also may want to consider using oral vancomycin (Vancocin) or fidaxomicin (Dificid) for treatment of Clostridium difficile infections, based on new evidence that found there is a higher cure rate for those treatments, compared with metronidazole.

Dr. Moriates and Dr. Herzke had no relevant financial conflicts.

On the big stage at HM19 in late March, Carrie Herzke, MD, FAAP, FACP, SFHM, and Christopher Moriates, MD, FACP, SFHM, undertook the daunting task of summarizing a year’s worth of research relevant to the practice of hospital medicine – all within the span of an hour.

As has been standard with the “Update in Hospital Medicine” session at previous SHM Annual Conferences, the presenters touched on lighter topics in the medical literature: a prospective cohort study that found drinking coffee was inversely associated with mortality, even for those who drink up to eight cups a day; a cross-sectional observational study in which patients noted that what a physician wears is an important consideration for them during care, with a white coat preferred over formal attire as the most highly rated preference in a clinical care setting; and a study from a pediatric journal in which researchers calculated the average transit time for a Lego figurine head ingested by an adult.

But Dr. Herzke and Dr. Moriates mainly covered more serious subjects. In an interview before the session, Dr. Herzke, associate vice chair for clinical affairs in the department of medicine at Johns Hopkins Medicine in Baltimore, said she and Dr. Moriates chose studies across the fields of infectious diseases, cardiology, and hematology that should make hospitalists question common practices and consider changing how they practice medicine at their home institution.

Dr. Moriates, assistant dean for health care value at the University of Texas at Austin, said in an interview that their topic choices reflected the breadth and diversity of patients taken care of by hospitalists.

For example, he noted during the HM19 session that results from several studies suggest hospitalists may soon choose oral antibiotics over IV antibiotics for care of certain patient populations: the recent POET trial suggests use of oral antibiotics for patients with left-sided infective endocarditis resulted in a lower length of stay in hospital (19 inpatient days) when compared with use of IV antibiotics (3 inpatient days and 17 additional treatment days post discharge), while the OVIVA trial found a lower but noninferior treatment failure rate among patients who received oral antibiotics for bone and joint infection, compared with IV antibiotics. Although these were both well-done studies, Dr. Moriates and Dr. Herzke emphasized that the results challenge widely accepted standards of care, and it may not yet be time for a paradigm shift.

Direct oral anticoagulants (DOACs) also are being studied in patients with end-stage renal disease (ESRD) and cancer, Dr. Herzke said, and apixaban (Eliquis) 5 mg appears to be the preferred dose for a lower risk of stroke and mortality in patients with ESRD and atrial fibrillation. The speakers said there are further studies being developed for management of AF in patients with heart failure and DOACs for patients with ESRD.

Another retrospective cohort study from research in the Massachusetts Public Health Dataset found that buprenorphine may have a number needed to treat of 50 for opioid use disorder, which Dr. Moriates said is close in proximity for the number needed to treat for aspirin. “It seems like it’s time for this to become standard of care,” he said.

The speakers also highlighted common practices hospitalists should stop performing based on the latest evidence.

In one example, they revealed that there is conflicting research on angiotensin-converting enzyme (ACE) inhibitors. One study found transient preoperative interruption of ACE inhibitors was associated with a reduction in intraoperative hypotension during a noncardiac, nonvascular surgery. A second study linked ACE inhibitor use with a reduction in all-cause mortality. However, long-term use of ACE inhibitors also appears to be associated with a 14% increase in lung cancers, with an increased incidence based on longer use duration.

Hospitalists should also be aware of recommendations from a study on oxygen therapy, Dr. Herzke noted, which found that extra oxygen therapy may harm patients with MI or stroke; as a result, hospitalists should “wean oxygen as tolerated” in these patients. In addition, hospitalists also may want to consider using oral vancomycin (Vancocin) or fidaxomicin (Dificid) for treatment of Clostridium difficile infections, based on new evidence that found there is a higher cure rate for those treatments, compared with metronidazole.

Dr. Moriates and Dr. Herzke had no relevant financial conflicts.

On the big stage at HM19 in late March, Carrie Herzke, MD, FAAP, FACP, SFHM, and Christopher Moriates, MD, FACP, SFHM, undertook the daunting task of summarizing a year’s worth of research relevant to the practice of hospital medicine – all within the span of an hour.

As has been standard with the “Update in Hospital Medicine” session at previous SHM Annual Conferences, the presenters touched on lighter topics in the medical literature: a prospective cohort study that found drinking coffee was inversely associated with mortality, even for those who drink up to eight cups a day; a cross-sectional observational study in which patients noted that what a physician wears is an important consideration for them during care, with a white coat preferred over formal attire as the most highly rated preference in a clinical care setting; and a study from a pediatric journal in which researchers calculated the average transit time for a Lego figurine head ingested by an adult.

But Dr. Herzke and Dr. Moriates mainly covered more serious subjects. In an interview before the session, Dr. Herzke, associate vice chair for clinical affairs in the department of medicine at Johns Hopkins Medicine in Baltimore, said she and Dr. Moriates chose studies across the fields of infectious diseases, cardiology, and hematology that should make hospitalists question common practices and consider changing how they practice medicine at their home institution.

Dr. Moriates, assistant dean for health care value at the University of Texas at Austin, said in an interview that their topic choices reflected the breadth and diversity of patients taken care of by hospitalists.

For example, he noted during the HM19 session that results from several studies suggest hospitalists may soon choose oral antibiotics over IV antibiotics for care of certain patient populations: the recent POET trial suggests use of oral antibiotics for patients with left-sided infective endocarditis resulted in a lower length of stay in hospital (19 inpatient days) when compared with use of IV antibiotics (3 inpatient days and 17 additional treatment days post discharge), while the OVIVA trial found a lower but noninferior treatment failure rate among patients who received oral antibiotics for bone and joint infection, compared with IV antibiotics. Although these were both well-done studies, Dr. Moriates and Dr. Herzke emphasized that the results challenge widely accepted standards of care, and it may not yet be time for a paradigm shift.

Direct oral anticoagulants (DOACs) also are being studied in patients with end-stage renal disease (ESRD) and cancer, Dr. Herzke said, and apixaban (Eliquis) 5 mg appears to be the preferred dose for a lower risk of stroke and mortality in patients with ESRD and atrial fibrillation. The speakers said there are further studies being developed for management of AF in patients with heart failure and DOACs for patients with ESRD.

Another retrospective cohort study from research in the Massachusetts Public Health Dataset found that buprenorphine may have a number needed to treat of 50 for opioid use disorder, which Dr. Moriates said is close in proximity for the number needed to treat for aspirin. “It seems like it’s time for this to become standard of care,” he said.

The speakers also highlighted common practices hospitalists should stop performing based on the latest evidence.

In one example, they revealed that there is conflicting research on angiotensin-converting enzyme (ACE) inhibitors. One study found transient preoperative interruption of ACE inhibitors was associated with a reduction in intraoperative hypotension during a noncardiac, nonvascular surgery. A second study linked ACE inhibitor use with a reduction in all-cause mortality. However, long-term use of ACE inhibitors also appears to be associated with a 14% increase in lung cancers, with an increased incidence based on longer use duration.

Hospitalists should also be aware of recommendations from a study on oxygen therapy, Dr. Herzke noted, which found that extra oxygen therapy may harm patients with MI or stroke; as a result, hospitalists should “wean oxygen as tolerated” in these patients. In addition, hospitalists also may want to consider using oral vancomycin (Vancocin) or fidaxomicin (Dificid) for treatment of Clostridium difficile infections, based on new evidence that found there is a higher cure rate for those treatments, compared with metronidazole.

Dr. Moriates and Dr. Herzke had no relevant financial conflicts.

Nivolumab, an immune checkpoint modulator, acts by binding to the programmed cell death 1 (PD-1) receptor on T cells, which blocks the inhibition of T cells. Nivolumab ultimately leads to stimulation of the T-cell response¹ and overcomes evasive adaptations of certain cancers. Cutaneous adverse events (AEs) have been reported in approximately 20% to 40% of patients treated with the anti–PD-1 class of drugs, including nivolumab.^2-4 The most common cutaneous AEs include pruritus; vitiligo; and various forms of rash, such as lichenoid dermatitis, psoriasiform eruptions, and bullous pemphigoid.^1-3,5-7 We report a patient with non–small cell lung cancer being treated with nivolumab who developed a bullous lichenoid eruption consistent with the diagnosis of lichen planus pemphigoides (LPP).

Case Report

An 87-year-old woman presented with a pruritic rash on the trunk and extremities of 3 weeks’ duration. Her medical history included stage IV non–small cell lung cancer, congestive heart failure, coronary artery disease, chronic kidney disease, and hypertension. Her long-term medications were ipratropium-albuterol, alendronate, amlodipine, aspirin, carvedilol, colesevelam, probiotic granules, and bumetanide. She was previously treated with carboplatin and docetaxel, which were discontinued secondary to fatigue, diarrhea, poor appetite, loss of taste, and a nonspecific rash. Six months later (approximately 3 months prior to the onset of cutaneous symptoms), she was started on nivolumab monotherapy every 14 days for a total of 9 infusions.

At the current presentation, physical examination revealed erythematous crusted erosions on the trunk and extremities and 1 flaccid bulla on the back. A punch biopsy revealed lichenoid dermatitis. The patient returned 2 weeks later with worsening of cutaneous manifestations, including more blisters and erosions. Figure 1 shows the clinical appearance of the eruption on the patient’s leg. At this time, additional biopsies revealed a subepidermal bullous lichenoid eruption with eosinophils (Figure 2). Direct immunofluorescence (DIF) was negative; however, indirect immunofluorescence (IIF) revealed weak linear staining for IgG antibodies along the basement membrane zone on monkey esophagus substrate. Examination of salt-split skin was noncontributory. The patient improved with a 2-week oral prednisone taper (starting at 40 mg daily). The dose was decreased incrementally over the course of 2 weeks from 40 mg to 20 mg to 0 mg. Because of the presumed grade 3 (severe) cutaneous drug eruption linked to nivolumab and further discussion with the medical oncology team, the patient decided to cease therapy. Since cessation of therapy, she has been seen twice for follow-up. At 2-month follow-up, she presented with drastic improvement of the eruption, and at 1 year she has continued to forego any further treatment for the stable and nonprogressing malignancy.

Comment

Immunotherapy
The interaction between the PD-1 receptor and its ligands, programmed death ligand 1 (PD-L1) and programmed death ligand 2, is an immune checkpoint.^8,9 Under normal physiologic conditions, this checkpoint serves to prevent autoimmunity.¹⁰ When the PD-1 receptor is left unbound, T cells are more inclined to mount an immune response. If the receptor is ligand bound, the response of T cells is suppressed via mechanisms such as anergy or apoptosis.⁸ Tumor cells are known to produce PD-L1 as an adaptive resistance mechanism to evade immunity.⁸ Nivolumab is a human monoclonal antibody that targets the PD-1 receptor, thereby preventing the interaction with its ligand and allowing for unsuppressed activity of T cells.¹⁰ This therapy ultimately blocks the tumor’s local immune suppression mechanisms, which allows T cells to recognize cancer antigens.¹⁰

Adverse Events
Dermatologic AEs are among the most common with nivolumab treatment. In a pooled retrospective analysis of melanoma patients, Weber et al⁹ found that 34% of 576 patients experience cutaneous any-grade AEs associated with nivolumab treatment, most commonly pruritus. It has been well documented that anti–PD-1 therapy AEs of the skin as well as other organ systems have a delayed onset of at least 1 month.⁹ The average time of onset for bullous eruptions associated with anti–PD-1 therapy has been reported to be approximately 12 weeks, with a range of 7 to 16.1 weeks.¹¹ Our patient had a bullous eruption with an onset of 12 weeks following initiation of treatment.

Although lichenoid reactions appear to be relatively common AEs of anti–PD-1 therapy,^2,5,6 only a small number of cases of bullous pemphigoid eruptions have been reported.⁷ It has been hypothesized that blockade of the PD-1/PD-L1 pathway increases production of hemidesmosomal protein BP180 autoantibody, which is involved in the pathogenesis of LPP.⁷ Bullous eruptions have not been reported in the use of anticytotoxic T-lymphocyte–associated protein 4 agents, which could indicate that such eruptions are specific to the anti–PD-1 class of drugs.⁷

Diagnosis
Our patient represents a rare drug reaction involving both lichenoid and bullous components. Our differential diagnosis included drug-induced bullous lichen planus (BLP) and drug-induced LPP. Differentiation of these diagnoses can be difficult. In fact, in 2017 Fujii et al¹² found reason to reprise the hypothesis that BLP is a transitional step toward LPP. The histologic evaluation of LPP differs depending on the type of lesion biopsied and can be indistinguishable from BLP as well as bullous pemphigoid. Therefore, clinical history and immunofluorescence should be used to make a diagnosis. Lichen planus pemphigoides typically will have linear IgG deposition along the basement membrane zone on both DIF and IIF, findings that will be negative in patients with BLP.¹³ Direct immunofluorescence findings in BLP include shaggy deposits of fibrin along the basement membrane zone. In this patient, DIF was negative, which may have been caused by variability among lesions in LPP, but IIF was positive. Given the clinicopathologic correlation, the diagnosis of LPP was made. Further studies, such as immunoblot and enzyme-linked immunosorbent assay, also can be used to aid diagnosis.

A similar presentation has been documented in a patient with metastatic melanoma.¹⁴ The diagnosis in this patient was LPP induced by pembrolizumab, which is another agent within the anti–PD-1 class. The Naranjo probability scale scored our patient’s eruption as a possible adverse drug reaction.¹⁵ Thus, other etiologies, such as a paraneoplastic process, cannot be completely ruled out. However, our patient has not had recurrence after 1 year, and the timing of the eruption appeared to be related to drug therapy, making alternative etiologies less likely.

Management
Cessation of nivolumab therapy and a short course of oral corticosteroid therapy led to marked improvement of symptoms. Given the emergent treatment of our patient, the resolution of her symptoms cannot be solely attributed to the cessation of nivolumab or to treatment with prednisone. Oral rather than topical corticosteroids were chosen because of the severity of the eruption. Topical corticosteroids and oral antihistamines can provide relief in less severe cases of bullous reactions to anti–PD-1 therapy.^7,11 This regimen also has proven to be effective in lichenoid dermatitis induced by anti–PD-1.²

Conclusion

We hope this case report will contribute to the growing body of evidence regarding recognition and management of unique reactions to cancer immunotherapies.

Nivolumab, an immune checkpoint modulator, acts by binding to the programmed cell death 1 (PD-1) receptor on T cells, which blocks the inhibition of T cells. Nivolumab ultimately leads to stimulation of the T-cell response¹ and overcomes evasive adaptations of certain cancers. Cutaneous adverse events (AEs) have been reported in approximately 20% to 40% of patients treated with the anti–PD-1 class of drugs, including nivolumab.^2-4 The most common cutaneous AEs include pruritus; vitiligo; and various forms of rash, such as lichenoid dermatitis, psoriasiform eruptions, and bullous pemphigoid.^1-3,5-7 We report a patient with non–small cell lung cancer being treated with nivolumab who developed a bullous lichenoid eruption consistent with the diagnosis of lichen planus pemphigoides (LPP).

Case Report

An 87-year-old woman presented with a pruritic rash on the trunk and extremities of 3 weeks’ duration. Her medical history included stage IV non–small cell lung cancer, congestive heart failure, coronary artery disease, chronic kidney disease, and hypertension. Her long-term medications were ipratropium-albuterol, alendronate, amlodipine, aspirin, carvedilol, colesevelam, probiotic granules, and bumetanide. She was previously treated with carboplatin and docetaxel, which were discontinued secondary to fatigue, diarrhea, poor appetite, loss of taste, and a nonspecific rash. Six months later (approximately 3 months prior to the onset of cutaneous symptoms), she was started on nivolumab monotherapy every 14 days for a total of 9 infusions.

At the current presentation, physical examination revealed erythematous crusted erosions on the trunk and extremities and 1 flaccid bulla on the back. A punch biopsy revealed lichenoid dermatitis. The patient returned 2 weeks later with worsening of cutaneous manifestations, including more blisters and erosions. Figure 1 shows the clinical appearance of the eruption on the patient’s leg. At this time, additional biopsies revealed a subepidermal bullous lichenoid eruption with eosinophils (Figure 2). Direct immunofluorescence (DIF) was negative; however, indirect immunofluorescence (IIF) revealed weak linear staining for IgG antibodies along the basement membrane zone on monkey esophagus substrate. Examination of salt-split skin was noncontributory. The patient improved with a 2-week oral prednisone taper (starting at 40 mg daily). The dose was decreased incrementally over the course of 2 weeks from 40 mg to 20 mg to 0 mg. Because of the presumed grade 3 (severe) cutaneous drug eruption linked to nivolumab and further discussion with the medical oncology team, the patient decided to cease therapy. Since cessation of therapy, she has been seen twice for follow-up. At 2-month follow-up, she presented with drastic improvement of the eruption, and at 1 year she has continued to forego any further treatment for the stable and nonprogressing malignancy.

Comment

Immunotherapy
The interaction between the PD-1 receptor and its ligands, programmed death ligand 1 (PD-L1) and programmed death ligand 2, is an immune checkpoint.^8,9 Under normal physiologic conditions, this checkpoint serves to prevent autoimmunity.¹⁰ When the PD-1 receptor is left unbound, T cells are more inclined to mount an immune response. If the receptor is ligand bound, the response of T cells is suppressed via mechanisms such as anergy or apoptosis.⁸ Tumor cells are known to produce PD-L1 as an adaptive resistance mechanism to evade immunity.⁸ Nivolumab is a human monoclonal antibody that targets the PD-1 receptor, thereby preventing the interaction with its ligand and allowing for unsuppressed activity of T cells.¹⁰ This therapy ultimately blocks the tumor’s local immune suppression mechanisms, which allows T cells to recognize cancer antigens.¹⁰

Adverse Events
Dermatologic AEs are among the most common with nivolumab treatment. In a pooled retrospective analysis of melanoma patients, Weber et al⁹ found that 34% of 576 patients experience cutaneous any-grade AEs associated with nivolumab treatment, most commonly pruritus. It has been well documented that anti–PD-1 therapy AEs of the skin as well as other organ systems have a delayed onset of at least 1 month.⁹ The average time of onset for bullous eruptions associated with anti–PD-1 therapy has been reported to be approximately 12 weeks, with a range of 7 to 16.1 weeks.¹¹ Our patient had a bullous eruption with an onset of 12 weeks following initiation of treatment.

Although lichenoid reactions appear to be relatively common AEs of anti–PD-1 therapy,^2,5,6 only a small number of cases of bullous pemphigoid eruptions have been reported.⁷ It has been hypothesized that blockade of the PD-1/PD-L1 pathway increases production of hemidesmosomal protein BP180 autoantibody, which is involved in the pathogenesis of LPP.⁷ Bullous eruptions have not been reported in the use of anticytotoxic T-lymphocyte–associated protein 4 agents, which could indicate that such eruptions are specific to the anti–PD-1 class of drugs.⁷

Diagnosis
Our patient represents a rare drug reaction involving both lichenoid and bullous components. Our differential diagnosis included drug-induced bullous lichen planus (BLP) and drug-induced LPP. Differentiation of these diagnoses can be difficult. In fact, in 2017 Fujii et al¹² found reason to reprise the hypothesis that BLP is a transitional step toward LPP. The histologic evaluation of LPP differs depending on the type of lesion biopsied and can be indistinguishable from BLP as well as bullous pemphigoid. Therefore, clinical history and immunofluorescence should be used to make a diagnosis. Lichen planus pemphigoides typically will have linear IgG deposition along the basement membrane zone on both DIF and IIF, findings that will be negative in patients with BLP.¹³ Direct immunofluorescence findings in BLP include shaggy deposits of fibrin along the basement membrane zone. In this patient, DIF was negative, which may have been caused by variability among lesions in LPP, but IIF was positive. Given the clinicopathologic correlation, the diagnosis of LPP was made. Further studies, such as immunoblot and enzyme-linked immunosorbent assay, also can be used to aid diagnosis.

A similar presentation has been documented in a patient with metastatic melanoma.¹⁴ The diagnosis in this patient was LPP induced by pembrolizumab, which is another agent within the anti–PD-1 class. The Naranjo probability scale scored our patient’s eruption as a possible adverse drug reaction.¹⁵ Thus, other etiologies, such as a paraneoplastic process, cannot be completely ruled out. However, our patient has not had recurrence after 1 year, and the timing of the eruption appeared to be related to drug therapy, making alternative etiologies less likely.

Management
Cessation of nivolumab therapy and a short course of oral corticosteroid therapy led to marked improvement of symptoms. Given the emergent treatment of our patient, the resolution of her symptoms cannot be solely attributed to the cessation of nivolumab or to treatment with prednisone. Oral rather than topical corticosteroids were chosen because of the severity of the eruption. Topical corticosteroids and oral antihistamines can provide relief in less severe cases of bullous reactions to anti–PD-1 therapy.^7,11 This regimen also has proven to be effective in lichenoid dermatitis induced by anti–PD-1.²

Conclusion

We hope this case report will contribute to the growing body of evidence regarding recognition and management of unique reactions to cancer immunotherapies.

Nivolumab, an immune checkpoint modulator, acts by binding to the programmed cell death 1 (PD-1) receptor on T cells, which blocks the inhibition of T cells. Nivolumab ultimately leads to stimulation of the T-cell response¹ and overcomes evasive adaptations of certain cancers. Cutaneous adverse events (AEs) have been reported in approximately 20% to 40% of patients treated with the anti–PD-1 class of drugs, including nivolumab.^2-4 The most common cutaneous AEs include pruritus; vitiligo; and various forms of rash, such as lichenoid dermatitis, psoriasiform eruptions, and bullous pemphigoid.^1-3,5-7 We report a patient with non–small cell lung cancer being treated with nivolumab who developed a bullous lichenoid eruption consistent with the diagnosis of lichen planus pemphigoides (LPP).

Case Report

An 87-year-old woman presented with a pruritic rash on the trunk and extremities of 3 weeks’ duration. Her medical history included stage IV non–small cell lung cancer, congestive heart failure, coronary artery disease, chronic kidney disease, and hypertension. Her long-term medications were ipratropium-albuterol, alendronate, amlodipine, aspirin, carvedilol, colesevelam, probiotic granules, and bumetanide. She was previously treated with carboplatin and docetaxel, which were discontinued secondary to fatigue, diarrhea, poor appetite, loss of taste, and a nonspecific rash. Six months later (approximately 3 months prior to the onset of cutaneous symptoms), she was started on nivolumab monotherapy every 14 days for a total of 9 infusions.

At the current presentation, physical examination revealed erythematous crusted erosions on the trunk and extremities and 1 flaccid bulla on the back. A punch biopsy revealed lichenoid dermatitis. The patient returned 2 weeks later with worsening of cutaneous manifestations, including more blisters and erosions. Figure 1 shows the clinical appearance of the eruption on the patient’s leg. At this time, additional biopsies revealed a subepidermal bullous lichenoid eruption with eosinophils (Figure 2). Direct immunofluorescence (DIF) was negative; however, indirect immunofluorescence (IIF) revealed weak linear staining for IgG antibodies along the basement membrane zone on monkey esophagus substrate. Examination of salt-split skin was noncontributory. The patient improved with a 2-week oral prednisone taper (starting at 40 mg daily). The dose was decreased incrementally over the course of 2 weeks from 40 mg to 20 mg to 0 mg. Because of the presumed grade 3 (severe) cutaneous drug eruption linked to nivolumab and further discussion with the medical oncology team, the patient decided to cease therapy. Since cessation of therapy, she has been seen twice for follow-up. At 2-month follow-up, she presented with drastic improvement of the eruption, and at 1 year she has continued to forego any further treatment for the stable and nonprogressing malignancy.

Comment

Immunotherapy
The interaction between the PD-1 receptor and its ligands, programmed death ligand 1 (PD-L1) and programmed death ligand 2, is an immune checkpoint.^8,9 Under normal physiologic conditions, this checkpoint serves to prevent autoimmunity.¹⁰ When the PD-1 receptor is left unbound, T cells are more inclined to mount an immune response. If the receptor is ligand bound, the response of T cells is suppressed via mechanisms such as anergy or apoptosis.⁸ Tumor cells are known to produce PD-L1 as an adaptive resistance mechanism to evade immunity.⁸ Nivolumab is a human monoclonal antibody that targets the PD-1 receptor, thereby preventing the interaction with its ligand and allowing for unsuppressed activity of T cells.¹⁰ This therapy ultimately blocks the tumor’s local immune suppression mechanisms, which allows T cells to recognize cancer antigens.¹⁰

Adverse Events
Dermatologic AEs are among the most common with nivolumab treatment. In a pooled retrospective analysis of melanoma patients, Weber et al⁹ found that 34% of 576 patients experience cutaneous any-grade AEs associated with nivolumab treatment, most commonly pruritus. It has been well documented that anti–PD-1 therapy AEs of the skin as well as other organ systems have a delayed onset of at least 1 month.⁹ The average time of onset for bullous eruptions associated with anti–PD-1 therapy has been reported to be approximately 12 weeks, with a range of 7 to 16.1 weeks.¹¹ Our patient had a bullous eruption with an onset of 12 weeks following initiation of treatment.

Although lichenoid reactions appear to be relatively common AEs of anti–PD-1 therapy,^2,5,6 only a small number of cases of bullous pemphigoid eruptions have been reported.⁷ It has been hypothesized that blockade of the PD-1/PD-L1 pathway increases production of hemidesmosomal protein BP180 autoantibody, which is involved in the pathogenesis of LPP.⁷ Bullous eruptions have not been reported in the use of anticytotoxic T-lymphocyte–associated protein 4 agents, which could indicate that such eruptions are specific to the anti–PD-1 class of drugs.⁷

Diagnosis
Our patient represents a rare drug reaction involving both lichenoid and bullous components. Our differential diagnosis included drug-induced bullous lichen planus (BLP) and drug-induced LPP. Differentiation of these diagnoses can be difficult. In fact, in 2017 Fujii et al¹² found reason to reprise the hypothesis that BLP is a transitional step toward LPP. The histologic evaluation of LPP differs depending on the type of lesion biopsied and can be indistinguishable from BLP as well as bullous pemphigoid. Therefore, clinical history and immunofluorescence should be used to make a diagnosis. Lichen planus pemphigoides typically will have linear IgG deposition along the basement membrane zone on both DIF and IIF, findings that will be negative in patients with BLP.¹³ Direct immunofluorescence findings in BLP include shaggy deposits of fibrin along the basement membrane zone. In this patient, DIF was negative, which may have been caused by variability among lesions in LPP, but IIF was positive. Given the clinicopathologic correlation, the diagnosis of LPP was made. Further studies, such as immunoblot and enzyme-linked immunosorbent assay, also can be used to aid diagnosis.

A similar presentation has been documented in a patient with metastatic melanoma.¹⁴ The diagnosis in this patient was LPP induced by pembrolizumab, which is another agent within the anti–PD-1 class. The Naranjo probability scale scored our patient’s eruption as a possible adverse drug reaction.¹⁵ Thus, other etiologies, such as a paraneoplastic process, cannot be completely ruled out. However, our patient has not had recurrence after 1 year, and the timing of the eruption appeared to be related to drug therapy, making alternative etiologies less likely.

Management
Cessation of nivolumab therapy and a short course of oral corticosteroid therapy led to marked improvement of symptoms. Given the emergent treatment of our patient, the resolution of her symptoms cannot be solely attributed to the cessation of nivolumab or to treatment with prednisone. Oral rather than topical corticosteroids were chosen because of the severity of the eruption. Topical corticosteroids and oral antihistamines can provide relief in less severe cases of bullous reactions to anti–PD-1 therapy.^7,11 This regimen also has proven to be effective in lichenoid dermatitis induced by anti–PD-1.²

Conclusion

We hope this case report will contribute to the growing body of evidence regarding recognition and management of unique reactions to cancer immunotherapies.

WASHINGTON – A program combining loan repayment and scholarships could encourage more medical students to pursue primary care upon graduation, according to a proposal presented at a meeting of the Medicare Payment Advisory Commission.

“A Medicare[-based] program would have a specific objective to encourage more physicians to enter primary care and provide primary care to beneficiaries,” MedPAC staffer Ariel Winter said. “By reducing educational debt, a Medicare-specific program would provide a financial incentive for physicians to choose primary care.”

Any program would face some challenges, Mr. Winter noted. Based on evidence, “it’s difficult to predict how physicians would respond if they were offered debt reduction in exchange for a commitment to practice primary care,” as financial considerations are not the only reason why physicians choose a specific career track.

Financing the program would also need to be considered. MedPAC staff recommended using a separate recommendation, one to end the Merit-based Incentive Payment System and use its $500 million put aside as MIPS bonuses to pay for any Medicare-based program.

Staff proposed a pilot program to “test the impact of different design choices on program operations, physician participation, and career choices,” he said. “Policymakers could use the results to improve the program and decide whether to expand it.”

MedPAC Vice Chairman Jon Christianson, PhD, suggested any program be tied to “physicians who practiced in areas where Medicare beneficiaries don’t have adequate access” to primary care doctors.

However, Mr. Winter noted that he is not aware of “any off-the-shelf system that identifies areas where there’s a problem, where there’s a shortage of clinicians for Medicare beneficiaries specifically. I am not sure how you would do that.”

MedPAC member Kathy Buto, former vice president of global health policy at Johnson & Johnson, questioned whether nurse practitioners and physician assistants should be included in the program, as they “are beginning to subspecialize and get out of primary care.” Mr. Winter said it is open for consideration.

MedPAC member Pat Wang, president and CEO of Healthfirst in New York, questioned whether a new program was needed or whether fixing of existing programs, “making them work better” is the way to go given the evidence that the effect of student debt on decision making is mixed.

She suggested that rather than targeting loan forgiveness, maybe the program should be structured more as a bonus payment rather than debt forgiveness as a means of incentivizing people who may not be concerned with debt forgiveness.

Ms. Buto added that questions of autonomy might also need to be addressed. “Physicians often feel like they don’t have control in Medicare, that they’re required to do a lot of things, and that they are subject to the fee schedule. If there were some way to grant more autonomy, control, and convey status that way, whether it has to do with greater flexibility in whatever, payment models and so on, that’s where I think you can begin to shift the status within primary care.”

MedPAC Chairman Francis Crosson, MD, recalled his time at Kaiser Permanente and noted their programs showed success because of the combination of a significant amount of money and time commitment (10 years).

The time commitment became an important part because after that long, physicians became a part of their communities and tended to stay.

“Two or 3 years, from my perspective and my experience, doesn’t work very well,” Dr. Crosson said. “But a significant period of time does, and a significant amount of money does seem to work.”

[email protected]

WASHINGTON – A program combining loan repayment and scholarships could encourage more medical students to pursue primary care upon graduation, according to a proposal presented at a meeting of the Medicare Payment Advisory Commission.

“A Medicare[-based] program would have a specific objective to encourage more physicians to enter primary care and provide primary care to beneficiaries,” MedPAC staffer Ariel Winter said. “By reducing educational debt, a Medicare-specific program would provide a financial incentive for physicians to choose primary care.”

Any program would face some challenges, Mr. Winter noted. Based on evidence, “it’s difficult to predict how physicians would respond if they were offered debt reduction in exchange for a commitment to practice primary care,” as financial considerations are not the only reason why physicians choose a specific career track.

Financing the program would also need to be considered. MedPAC staff recommended using a separate recommendation, one to end the Merit-based Incentive Payment System and use its $500 million put aside as MIPS bonuses to pay for any Medicare-based program.

Staff proposed a pilot program to “test the impact of different design choices on program operations, physician participation, and career choices,” he said. “Policymakers could use the results to improve the program and decide whether to expand it.”

MedPAC Vice Chairman Jon Christianson, PhD, suggested any program be tied to “physicians who practiced in areas where Medicare beneficiaries don’t have adequate access” to primary care doctors.

However, Mr. Winter noted that he is not aware of “any off-the-shelf system that identifies areas where there’s a problem, where there’s a shortage of clinicians for Medicare beneficiaries specifically. I am not sure how you would do that.”

MedPAC member Kathy Buto, former vice president of global health policy at Johnson & Johnson, questioned whether nurse practitioners and physician assistants should be included in the program, as they “are beginning to subspecialize and get out of primary care.” Mr. Winter said it is open for consideration.

MedPAC member Pat Wang, president and CEO of Healthfirst in New York, questioned whether a new program was needed or whether fixing of existing programs, “making them work better” is the way to go given the evidence that the effect of student debt on decision making is mixed.

She suggested that rather than targeting loan forgiveness, maybe the program should be structured more as a bonus payment rather than debt forgiveness as a means of incentivizing people who may not be concerned with debt forgiveness.

Ms. Buto added that questions of autonomy might also need to be addressed. “Physicians often feel like they don’t have control in Medicare, that they’re required to do a lot of things, and that they are subject to the fee schedule. If there were some way to grant more autonomy, control, and convey status that way, whether it has to do with greater flexibility in whatever, payment models and so on, that’s where I think you can begin to shift the status within primary care.”

MedPAC Chairman Francis Crosson, MD, recalled his time at Kaiser Permanente and noted their programs showed success because of the combination of a significant amount of money and time commitment (10 years).

The time commitment became an important part because after that long, physicians became a part of their communities and tended to stay.

“Two or 3 years, from my perspective and my experience, doesn’t work very well,” Dr. Crosson said. “But a significant period of time does, and a significant amount of money does seem to work.”

[email protected]

WASHINGTON – A program combining loan repayment and scholarships could encourage more medical students to pursue primary care upon graduation, according to a proposal presented at a meeting of the Medicare Payment Advisory Commission.

“A Medicare[-based] program would have a specific objective to encourage more physicians to enter primary care and provide primary care to beneficiaries,” MedPAC staffer Ariel Winter said. “By reducing educational debt, a Medicare-specific program would provide a financial incentive for physicians to choose primary care.”

Any program would face some challenges, Mr. Winter noted. Based on evidence, “it’s difficult to predict how physicians would respond if they were offered debt reduction in exchange for a commitment to practice primary care,” as financial considerations are not the only reason why physicians choose a specific career track.

Financing the program would also need to be considered. MedPAC staff recommended using a separate recommendation, one to end the Merit-based Incentive Payment System and use its $500 million put aside as MIPS bonuses to pay for any Medicare-based program.

Staff proposed a pilot program to “test the impact of different design choices on program operations, physician participation, and career choices,” he said. “Policymakers could use the results to improve the program and decide whether to expand it.”

MedPAC Vice Chairman Jon Christianson, PhD, suggested any program be tied to “physicians who practiced in areas where Medicare beneficiaries don’t have adequate access” to primary care doctors.

However, Mr. Winter noted that he is not aware of “any off-the-shelf system that identifies areas where there’s a problem, where there’s a shortage of clinicians for Medicare beneficiaries specifically. I am not sure how you would do that.”

MedPAC member Kathy Buto, former vice president of global health policy at Johnson & Johnson, questioned whether nurse practitioners and physician assistants should be included in the program, as they “are beginning to subspecialize and get out of primary care.” Mr. Winter said it is open for consideration.

MedPAC member Pat Wang, president and CEO of Healthfirst in New York, questioned whether a new program was needed or whether fixing of existing programs, “making them work better” is the way to go given the evidence that the effect of student debt on decision making is mixed.

She suggested that rather than targeting loan forgiveness, maybe the program should be structured more as a bonus payment rather than debt forgiveness as a means of incentivizing people who may not be concerned with debt forgiveness.

Ms. Buto added that questions of autonomy might also need to be addressed. “Physicians often feel like they don’t have control in Medicare, that they’re required to do a lot of things, and that they are subject to the fee schedule. If there were some way to grant more autonomy, control, and convey status that way, whether it has to do with greater flexibility in whatever, payment models and so on, that’s where I think you can begin to shift the status within primary care.”

MedPAC Chairman Francis Crosson, MD, recalled his time at Kaiser Permanente and noted their programs showed success because of the combination of a significant amount of money and time commitment (10 years).

The time commitment became an important part because after that long, physicians became a part of their communities and tended to stay.

“Two or 3 years, from my perspective and my experience, doesn’t work very well,” Dr. Crosson said. “But a significant period of time does, and a significant amount of money does seem to work.”

[email protected]

Hospitalists can have a role in helping patients choose and receive high-value care from the vast array of health care choices they face. Helping them use quality and cost reports is one way to do that, according to a recent editorial by Jeffrey T. Kullgren, MD, MS, MPH.

We know that if consumers used public reporting of quality and costs to choose facilities that generate the best health outcomes for the resources utilized, it might improve the overall value of health care spending. But most people choose health care services based on personal recommendations or the requirements of their insurance network. Even if they wanted to use reports of quality or cost, the information in these reports is meant for providers and would likely be unhelpful for consumers.

Research suggests that different presentation of the information could make a difference. “Simpler presentations of information in public reports may be more likely to help consumers choose higher-value providers and facilities,” Dr. Kullgren said.

He concluded that consumers may also need additional incentives, “such as financial incentives to encourage high-value choices or programs that educate consumers about how to use cost and quality information when seeking care,” he said.

There’s an opportunity for hospitalists to help consumers learn to use that information. “This strategy would approach consumerism as a teachable health behavior and could be particularly helpful for consumers with ongoing medical needs who face high cost sharing,” he wrote.

“Some hospitalists may be involved in the implementation of programs to publicly report quality and costs for their institutions,” he said. “Others may treat patients who have chosen hospitals based on publicly reported information, or patients who might be interested in using such information to choose sites of postdischarge outpatient care. In each of these cases, it is important for hospitalists to understand the opportunities and limits of such public reports so as to best help patients receive high-value care.” 

Reference

Kullgren JT. Helping consumers make high value health care choices: The devil is in the details. Health Serv Res. 2018;53(4). http://www.hsr.org/hsr/abstract.jsp?aid=53301961729.

Hospitalists can have a role in helping patients choose and receive high-value care from the vast array of health care choices they face. Helping them use quality and cost reports is one way to do that, according to a recent editorial by Jeffrey T. Kullgren, MD, MS, MPH.

We know that if consumers used public reporting of quality and costs to choose facilities that generate the best health outcomes for the resources utilized, it might improve the overall value of health care spending. But most people choose health care services based on personal recommendations or the requirements of their insurance network. Even if they wanted to use reports of quality or cost, the information in these reports is meant for providers and would likely be unhelpful for consumers.

Research suggests that different presentation of the information could make a difference. “Simpler presentations of information in public reports may be more likely to help consumers choose higher-value providers and facilities,” Dr. Kullgren said.

He concluded that consumers may also need additional incentives, “such as financial incentives to encourage high-value choices or programs that educate consumers about how to use cost and quality information when seeking care,” he said.

There’s an opportunity for hospitalists to help consumers learn to use that information. “This strategy would approach consumerism as a teachable health behavior and could be particularly helpful for consumers with ongoing medical needs who face high cost sharing,” he wrote.

“Some hospitalists may be involved in the implementation of programs to publicly report quality and costs for their institutions,” he said. “Others may treat patients who have chosen hospitals based on publicly reported information, or patients who might be interested in using such information to choose sites of postdischarge outpatient care. In each of these cases, it is important for hospitalists to understand the opportunities and limits of such public reports so as to best help patients receive high-value care.” 

Reference

Kullgren JT. Helping consumers make high value health care choices: The devil is in the details. Health Serv Res. 2018;53(4). http://www.hsr.org/hsr/abstract.jsp?aid=53301961729.

Hospitalists can have a role in helping patients choose and receive high-value care from the vast array of health care choices they face. Helping them use quality and cost reports is one way to do that, according to a recent editorial by Jeffrey T. Kullgren, MD, MS, MPH.

We know that if consumers used public reporting of quality and costs to choose facilities that generate the best health outcomes for the resources utilized, it might improve the overall value of health care spending. But most people choose health care services based on personal recommendations or the requirements of their insurance network. Even if they wanted to use reports of quality or cost, the information in these reports is meant for providers and would likely be unhelpful for consumers.

Research suggests that different presentation of the information could make a difference. “Simpler presentations of information in public reports may be more likely to help consumers choose higher-value providers and facilities,” Dr. Kullgren said.

He concluded that consumers may also need additional incentives, “such as financial incentives to encourage high-value choices or programs that educate consumers about how to use cost and quality information when seeking care,” he said.

There’s an opportunity for hospitalists to help consumers learn to use that information. “This strategy would approach consumerism as a teachable health behavior and could be particularly helpful for consumers with ongoing medical needs who face high cost sharing,” he wrote.

“Some hospitalists may be involved in the implementation of programs to publicly report quality and costs for their institutions,” he said. “Others may treat patients who have chosen hospitals based on publicly reported information, or patients who might be interested in using such information to choose sites of postdischarge outpatient care. In each of these cases, it is important for hospitalists to understand the opportunities and limits of such public reports so as to best help patients receive high-value care.” 

Reference

Kullgren JT. Helping consumers make high value health care choices: The devil is in the details. Health Serv Res. 2018;53(4). http://www.hsr.org/hsr/abstract.jsp?aid=53301961729.

The Diagnosis:  Primary Cutaneous Perivascular Epithelioid Cell Tumor  

Perivascular epithelioid cell tumors (PEComas) were first described in 1996.¹ They comprise a family of rare mesenchymal neoplasms that have a unique characteristic of staining positive for melanocytic and smooth muscle markers on immunohistochemistry.² These neoplasms have been described in many areas of the body including the uterus, bladder, heart, pancreas, and prostate. The majority of PEComas are extracutaneous, with only 8% of reported cases originating on the skin.³ A case of primary cutaneous PEComa (pcPEComa) was described in 2003.⁴ The primary cutaneous form is extremely rare.^3,5-7  

A broad deep shave biopsy was performed in our patient in an attempt to sample the entire lesion. Histopathologic examination of the nodule demonstrated a dermal neoplasm comprised of a diffuse proliferation of large polygonal cells with abundant clear cytoplasm, fine chromatin, and prominent nucleoli (Figure 1A). Higher-power magnification showed moderate nuclear pleomorphism and only rare mitotic figures (Figure 1B).

Immunohistochemical staining revealed positivity for myomelanocytic markers with positivity for human melanoma black 45 (HMB-45)(Figure 2) and desmin (not shown). Additionally, the tumor was positive for CD163 and negative for smooth muscle actin, cytokeratin, and S-100 protein.  

Perivascular epithelioid cell tumors are characterized histologically as mesenchymal neoplasms containing large epithelioid to spindled cells with a slightly granular, vacuolated cytoplasm. These cells often are found in close proximity to vascular structures.^3,5,8 The hallmark of PEComas is the expression of both melanocytic and muscle markers.^3,8 A review of staining patterns of pcPEComas emphasized that immunophenotypes between visceral and primary cutaneous forms may vary considerably.^3,5,8 The most consistent and sensitive melanocytic marker is HMB-45 (88%-92% positive).^3,8 Positive Melan-A staining varies in the literature from 0% to 50% of cases.³ Our patient's neoplasm expressed the characteristic myomelanocytic immunophenotype with both HMB-45 and desmin positivity. 

Given the histologic characteristics, these lesions can be mistaken for melanocytic and other nonmelanocytic tumors with a clear cell morphology such as balloon cell nevus, hypomelanotic blue nevus, and melanoma.^2,3 A pigmented case of pcPEComa was reported in 2015 and was originally diagnosed as metastatic melanoma.⁶ Unlike pcPEComa, melanoma usually stains positive with S-100 protein in up to 99% of cases⁸ and is negative for muscle markers; however, a case series reported S-100 protein positivity in 38% of pcPEComas.³ Nonmelanocytic neoplasms in the histologic differential diagnosis include clear cell sarcoma and clear cell renal cell carcinoma, both of which show immunoreactivity for cytokeratin.⁹  

Histologic criteria exist for establishing malignancy potential for visceral PEComas but not for pcPEComas, though it has been suggested that the same malignancy criteria should be applied to pcPEComas.^3,9 Features associated with malignancy include size greater than 8 cm, mitotic activity greater than 1 mitosis per 50 high-power fields, infiltrative growth pattern, high nuclear grade, necrosis, and vascular invasion. Based on these criteria, fulfilling 2 or more features technically classifies the lesion as malignant, 1 feature classifies it as uncertain malignant potential, and a lack of these features renders the lesion benign.⁹  

The overwhelming majority of pcPEComas are considered benign. One case of pcPEComa was considered malignant with a high mitotic rate (5 mitoses per 10 high-power fields) and nuclear atypia.¹⁰ Further workup with thoracic computed tomography and positron emission tomography-computed tomography was negative for metastasis. Treatment with wide excision and radiotherapy was performed with no sign of recurrence at 24-month follow-up.¹⁰  

Although pcPEComas arising from the dermis seem to be benign overall, PEComas originating from the subcutaneous tissue may have greater malignancy potential. Two cases of subcutaneous PEComas presenting as nodules resulted in metastasis; one case had local nodal metastasis and another developed metastasis to the lungs months later.^10,11 

The Diagnosis:  Primary Cutaneous Perivascular Epithelioid Cell Tumor  

Perivascular epithelioid cell tumors (PEComas) were first described in 1996.¹ They comprise a family of rare mesenchymal neoplasms that have a unique characteristic of staining positive for melanocytic and smooth muscle markers on immunohistochemistry.² These neoplasms have been described in many areas of the body including the uterus, bladder, heart, pancreas, and prostate. The majority of PEComas are extracutaneous, with only 8% of reported cases originating on the skin.³ A case of primary cutaneous PEComa (pcPEComa) was described in 2003.⁴ The primary cutaneous form is extremely rare.^3,5-7  

A broad deep shave biopsy was performed in our patient in an attempt to sample the entire lesion. Histopathologic examination of the nodule demonstrated a dermal neoplasm comprised of a diffuse proliferation of large polygonal cells with abundant clear cytoplasm, fine chromatin, and prominent nucleoli (Figure 1A). Higher-power magnification showed moderate nuclear pleomorphism and only rare mitotic figures (Figure 1B).

Immunohistochemical staining revealed positivity for myomelanocytic markers with positivity for human melanoma black 45 (HMB-45)(Figure 2) and desmin (not shown). Additionally, the tumor was positive for CD163 and negative for smooth muscle actin, cytokeratin, and S-100 protein.  

Perivascular epithelioid cell tumors are characterized histologically as mesenchymal neoplasms containing large epithelioid to spindled cells with a slightly granular, vacuolated cytoplasm. These cells often are found in close proximity to vascular structures.^3,5,8 The hallmark of PEComas is the expression of both melanocytic and muscle markers.^3,8 A review of staining patterns of pcPEComas emphasized that immunophenotypes between visceral and primary cutaneous forms may vary considerably.^3,5,8 The most consistent and sensitive melanocytic marker is HMB-45 (88%-92% positive).^3,8 Positive Melan-A staining varies in the literature from 0% to 50% of cases.³ Our patient's neoplasm expressed the characteristic myomelanocytic immunophenotype with both HMB-45 and desmin positivity. 

Given the histologic characteristics, these lesions can be mistaken for melanocytic and other nonmelanocytic tumors with a clear cell morphology such as balloon cell nevus, hypomelanotic blue nevus, and melanoma.^2,3 A pigmented case of pcPEComa was reported in 2015 and was originally diagnosed as metastatic melanoma.⁶ Unlike pcPEComa, melanoma usually stains positive with S-100 protein in up to 99% of cases⁸ and is negative for muscle markers; however, a case series reported S-100 protein positivity in 38% of pcPEComas.³ Nonmelanocytic neoplasms in the histologic differential diagnosis include clear cell sarcoma and clear cell renal cell carcinoma, both of which show immunoreactivity for cytokeratin.⁹  

Histologic criteria exist for establishing malignancy potential for visceral PEComas but not for pcPEComas, though it has been suggested that the same malignancy criteria should be applied to pcPEComas.^3,9 Features associated with malignancy include size greater than 8 cm, mitotic activity greater than 1 mitosis per 50 high-power fields, infiltrative growth pattern, high nuclear grade, necrosis, and vascular invasion. Based on these criteria, fulfilling 2 or more features technically classifies the lesion as malignant, 1 feature classifies it as uncertain malignant potential, and a lack of these features renders the lesion benign.⁹  

The overwhelming majority of pcPEComas are considered benign. One case of pcPEComa was considered malignant with a high mitotic rate (5 mitoses per 10 high-power fields) and nuclear atypia.¹⁰ Further workup with thoracic computed tomography and positron emission tomography-computed tomography was negative for metastasis. Treatment with wide excision and radiotherapy was performed with no sign of recurrence at 24-month follow-up.¹⁰  

Although pcPEComas arising from the dermis seem to be benign overall, PEComas originating from the subcutaneous tissue may have greater malignancy potential. Two cases of subcutaneous PEComas presenting as nodules resulted in metastasis; one case had local nodal metastasis and another developed metastasis to the lungs months later.^10,11 

The Diagnosis:  Primary Cutaneous Perivascular Epithelioid Cell Tumor  

Perivascular epithelioid cell tumors (PEComas) were first described in 1996.¹ They comprise a family of rare mesenchymal neoplasms that have a unique characteristic of staining positive for melanocytic and smooth muscle markers on immunohistochemistry.² These neoplasms have been described in many areas of the body including the uterus, bladder, heart, pancreas, and prostate. The majority of PEComas are extracutaneous, with only 8% of reported cases originating on the skin.³ A case of primary cutaneous PEComa (pcPEComa) was described in 2003.⁴ The primary cutaneous form is extremely rare.^3,5-7  

A broad deep shave biopsy was performed in our patient in an attempt to sample the entire lesion. Histopathologic examination of the nodule demonstrated a dermal neoplasm comprised of a diffuse proliferation of large polygonal cells with abundant clear cytoplasm, fine chromatin, and prominent nucleoli (Figure 1A). Higher-power magnification showed moderate nuclear pleomorphism and only rare mitotic figures (Figure 1B).

Immunohistochemical staining revealed positivity for myomelanocytic markers with positivity for human melanoma black 45 (HMB-45)(Figure 2) and desmin (not shown). Additionally, the tumor was positive for CD163 and negative for smooth muscle actin, cytokeratin, and S-100 protein.  

Perivascular epithelioid cell tumors are characterized histologically as mesenchymal neoplasms containing large epithelioid to spindled cells with a slightly granular, vacuolated cytoplasm. These cells often are found in close proximity to vascular structures.^3,5,8 The hallmark of PEComas is the expression of both melanocytic and muscle markers.^3,8 A review of staining patterns of pcPEComas emphasized that immunophenotypes between visceral and primary cutaneous forms may vary considerably.^3,5,8 The most consistent and sensitive melanocytic marker is HMB-45 (88%-92% positive).^3,8 Positive Melan-A staining varies in the literature from 0% to 50% of cases.³ Our patient's neoplasm expressed the characteristic myomelanocytic immunophenotype with both HMB-45 and desmin positivity. 

Given the histologic characteristics, these lesions can be mistaken for melanocytic and other nonmelanocytic tumors with a clear cell morphology such as balloon cell nevus, hypomelanotic blue nevus, and melanoma.^2,3 A pigmented case of pcPEComa was reported in 2015 and was originally diagnosed as metastatic melanoma.⁶ Unlike pcPEComa, melanoma usually stains positive with S-100 protein in up to 99% of cases⁸ and is negative for muscle markers; however, a case series reported S-100 protein positivity in 38% of pcPEComas.³ Nonmelanocytic neoplasms in the histologic differential diagnosis include clear cell sarcoma and clear cell renal cell carcinoma, both of which show immunoreactivity for cytokeratin.⁹  

Histologic criteria exist for establishing malignancy potential for visceral PEComas but not for pcPEComas, though it has been suggested that the same malignancy criteria should be applied to pcPEComas.^3,9 Features associated with malignancy include size greater than 8 cm, mitotic activity greater than 1 mitosis per 50 high-power fields, infiltrative growth pattern, high nuclear grade, necrosis, and vascular invasion. Based on these criteria, fulfilling 2 or more features technically classifies the lesion as malignant, 1 feature classifies it as uncertain malignant potential, and a lack of these features renders the lesion benign.⁹  

The overwhelming majority of pcPEComas are considered benign. One case of pcPEComa was considered malignant with a high mitotic rate (5 mitoses per 10 high-power fields) and nuclear atypia.¹⁰ Further workup with thoracic computed tomography and positron emission tomography-computed tomography was negative for metastasis. Treatment with wide excision and radiotherapy was performed with no sign of recurrence at 24-month follow-up.¹⁰  

Although pcPEComas arising from the dermis seem to be benign overall, PEComas originating from the subcutaneous tissue may have greater malignancy potential. Two cases of subcutaneous PEComas presenting as nodules resulted in metastasis; one case had local nodal metastasis and another developed metastasis to the lungs months later.^10,11 

As a second-year gastroenterology fellow, I designed a prospective, double-blind randomized, controlled trial for vitamin D repletion in patients with Crohn’s disease at a referral inflammatory bowel disease (IBD) center. I had the support of a dedicated research team, several mentors, and a 2-year time frame in which to complete this study. Intellectually curious and academically eager, I labored over a grant application that I did not receive. Under generous financial support from my department, I forged on and opened the trial for enrollment at the start of my advanced IBD fellowship year. However, we experienced recruitment challenges that ultimately led to the study’s premature termination. Through this journey, I gained invaluable experience that will continue to serve me – and, I hope, the reader – as I progress in my career. Below are some important insights gleaned from this experience that may benefit others interested in clinical trial design.

Know your “why” (personally and clinically)

Asked to reflect on their career path, experts tend to recount their “being in the right place at the right time” and having “good mentors.” While luck and good mentorship are necessary, I propose that doing your homework is equally as important. Before ambling down the path of an investigator-led trial, I urge a hard pause to reflect on your “why.” The personal “why” of “getting into fellowship,” “advancement in the department,” or “learning more about the principles of research,” are all valid. But I suggest a deeper dive is in order. Successful clinical trials require resources, a substantial time commitment, lots of sweat and maybe a few tears. In the ideal setting, your trial experience will serve as the foundation for a compelling personal narrative and might help launch a productive clinical research career. With stakes that high, asking the tough questions is critical.

The clinical “why” is just as critical. We press our attendings on why they used this drug or that clip, so don’t be afraid to ask whether this is a space in which others have succeeded. Or conversely, why is there such a large gap in the literature? I remember emailing the world’s expert about my topic because the published data were so murky. He had more questions than answers which, in retrospect, should have raised red flags about the ability to design a sound study. It is equally important to determine if patients are vested in the research question. A successful clinical trial hinges on subject participation, often outside their clinic visit. Patients with complex chronic diseases spend a lot of time navigating the health care system. Participating in a clinical trial needs to be meaningful to them if you want your patients to fully engage. Thoughtfully answering these questions on the front end – for yourself and the study in question – will improve both your experience and the ultimate outcome exponentially.

Identify your village (and listen to them)

Designing a clinical trial truly takes a village, and you need to identify the villagers early. As trainees, the value of mentorship is frequently underscored. But the importance of, and the nuance involved in managing, collaborating, and support cannot be overstated. Meet with a biostatistician to ensure your sample size calculations are correct. Work closely with the research pharmacist to ensure the medication formulation is available; decide on the manner of distribution so as not to inconvenience subjects; create a budget with an experienced manager. Seek out research coordinators often for assistance in creating case report forms, learning appropriate documentation, and crafting responses to Institutional Review Board concerns. Ask clinic personnel about arranging consent or follow-up visits around subjects’ clinic appointments. Present a draft of the protocol to your colleagues, as you will ultimately need them on board to recruit patients. And most importantly, listen to them ... all of them. Get your biases in check and write down all constructive criticism. Thoughtfully address each concern encountered to your satisfaction (and your mentor’s) and present to your village again. Rinse and repeat. Throw nothing under the rug, because if you do, it will eventually rear its head while you are in the throes of the study.

In retrospect, there were concerns raised by faculty and grant reviewers that I did not adequately address. First was the feasibility of screening, recruiting, and enrolling 80 patients during a busy clinical fellowship. While I took this criticism as a reflection of my personal commitment to the project, it was actually a call to consider the impact on clinical (and familial) responsibilities. But as I started enrolling patients, I realized there were logistic issues implied in this suggestion. I could not recruit subjects in Clinic A if I was assigned to see patients at the same time in Clinic B. Patients were not likely to come back another day for study-related discussions. Second, I designed eligibility criteria to make the data as clean as possible. Limiting the study to subjects with Crohn’s disease, in clinical and biochemical remission, without complications of their disease, who also have vitamin deficiency, may be an unrealistic recipe to recruit 80 people in a limited period of time. Finally, I designed laboratory follow-up schedules based on the pharmacokinetics of the drug alone, failing to consider the clinical milieu from which study subjects were recruited. Neglecting the fact that many patients obtain labs with their infusions, my study increased lab draw burden, heaped more patient reminders onto my plate – and more concerning – decreased overall study compliance. In short, trial design cannot be done in a vacuum or by just poring over published data. There are logistical and patient-related considerations that require early input from physicians and clinical staff in order for all the moving parts of a clinical trial to successfully work in harmony.
 

Create a timetable and follow it

Make a recruitment timetable very early on in the enrollment period. Set up biweekly meetings with mentors to discuss enrollment numbers and reflect on any unforeseen challenges. And be sure to celebrate the wins as well – not matter how small. In our study, falling behind on recruitment goals forced me to amend the stringent eligibility criteria and add additional manpower to help with reminders for laboratory follow-up and patient screening. These pivots caused study delays and cost resources. Ultimately, having a timetable forced me to take pause when it became clear I could not finish the study in the allotted time.

Know when to fold ’em

Knowing when to close a study is far easier said than done. The sunk cost fallacy says it is much harder to abandon a project after investing so many resources into it. For us, it was the recruitment timetable that gave us pause. Finishing trial accrual by the end of my advanced fellowship year was wholly unfeasible. When it became clear that nobody in the department could see it through to completion, I was propelled to terminate the study. If there is concern about termination, I suggest sending the protocol, recruitment numbers, and timeline to an outside colleague for a second, unbiased opinion. Review the already compiled data for any notable findings worthy of a smaller publication. It is said, we often learn more from our failures than our successes. The experience described herein – largely in part to my mentors, collaborators, and the patients who put their faith in me – translates to a lasting, invaluable win.

Mentor’s note

Clinical research is hard. Many trainees meet with me to “get involved” in clinical research, and the challenge as a mentor is to identify a project appropriate to the level of training and provide the infrastructure and resources to facilitate success for the motivated trainee. Trainees have various goals of their involvement in research – to foster a relationship in the hopes of receiving a strong letter of support, to facilitate getting into a competitive training program, and/or to publish. My goal as a mentor is to help my trainees reach their goals, but as a clinical researcher, I look for the trainee’s desire to engage with and learn the research process, with the ancillary potential for a letter, for acceptance to a program, or for publication.

This particular study, a randomized, controlled trial of vitamin D in patients with Crohn’s disease, involved an enormous undertaking by a very motivated trainee who took the project from its inception; to putting a thoughtful grant proposal together; to developing a full clinical trial protocol with its ancillary regulatory documents; and obtaining institutional review board approval, statistician input, pharmacy support, and buy-in from faculty and ancillary staff stakeholders. The study ultimately failed because of low enrollment – patients did not want to participate (for reasons elucidated above) – not because of poor design or execution of the myriad components of a prospective clinical trial. Low enrollment has led to the failure of many otherwise excellent studies, including several in our field of IBD.^1,2 As a mentor, it is rational to accept blame for the failure of a trainee project; how could I have better foreseen the outcome of this study? Could this have been prevented with more support, more oversight, or more “micromanagement,” to the potential detriment of fostering independence?

Ultimately, the value of clinical research to trainees is multifaceted. If the goal was a first-author publication with high clinical impact, this trial failed. But if the goal was to learn about the clinical trial process, this study was a resounding success. Ultimately, it behooves trainees and their mentors to engage in early, upfront conversations about research. What are the goals? What does success look like? What if the trial fails? By shifting the focus from the success of the project to the success of the mentorship and educational process, even failed projects are resounding successes, upon which future careers can be further developed.
 

References

1. Kan S et al. When subjects violate the research covenant: Lessons learned from a failed clinical trial of fecal microbiota transplantation. Am J Gastroenterol 2016;111:1508-10.

2. Dassopoulos T et al. Randomised clinical trial: Individualised vs.weight-based dosing of azathioprine in Crohn’s disease. Aliment Pharmacol Ther. 2014 Jan;39(2):163-75.

Dr. Cohen is an inflammatory bowel disease fellow, inflammatory bowel disease center, division of gastroenterology and hepatology, department of medicine, Cedars-Sinai Medical Center, Los Angeles. Dr. Melmed is director, inflammatory bowel disease clinical research and codirector, clinical inflammatory bowel disease, inflammatory bowel disease center, division of gastroenterology and hepatology, department of medicine, Cedars-Sinai Medical Center, Los Angeles.

As a second-year gastroenterology fellow, I designed a prospective, double-blind randomized, controlled trial for vitamin D repletion in patients with Crohn’s disease at a referral inflammatory bowel disease (IBD) center. I had the support of a dedicated research team, several mentors, and a 2-year time frame in which to complete this study. Intellectually curious and academically eager, I labored over a grant application that I did not receive. Under generous financial support from my department, I forged on and opened the trial for enrollment at the start of my advanced IBD fellowship year. However, we experienced recruitment challenges that ultimately led to the study’s premature termination. Through this journey, I gained invaluable experience that will continue to serve me – and, I hope, the reader – as I progress in my career. Below are some important insights gleaned from this experience that may benefit others interested in clinical trial design.

Know your “why” (personally and clinically)

Asked to reflect on their career path, experts tend to recount their “being in the right place at the right time” and having “good mentors.” While luck and good mentorship are necessary, I propose that doing your homework is equally as important. Before ambling down the path of an investigator-led trial, I urge a hard pause to reflect on your “why.” The personal “why” of “getting into fellowship,” “advancement in the department,” or “learning more about the principles of research,” are all valid. But I suggest a deeper dive is in order. Successful clinical trials require resources, a substantial time commitment, lots of sweat and maybe a few tears. In the ideal setting, your trial experience will serve as the foundation for a compelling personal narrative and might help launch a productive clinical research career. With stakes that high, asking the tough questions is critical.

The clinical “why” is just as critical. We press our attendings on why they used this drug or that clip, so don’t be afraid to ask whether this is a space in which others have succeeded. Or conversely, why is there such a large gap in the literature? I remember emailing the world’s expert about my topic because the published data were so murky. He had more questions than answers which, in retrospect, should have raised red flags about the ability to design a sound study. It is equally important to determine if patients are vested in the research question. A successful clinical trial hinges on subject participation, often outside their clinic visit. Patients with complex chronic diseases spend a lot of time navigating the health care system. Participating in a clinical trial needs to be meaningful to them if you want your patients to fully engage. Thoughtfully answering these questions on the front end – for yourself and the study in question – will improve both your experience and the ultimate outcome exponentially.

Identify your village (and listen to them)

Designing a clinical trial truly takes a village, and you need to identify the villagers early. As trainees, the value of mentorship is frequently underscored. But the importance of, and the nuance involved in managing, collaborating, and support cannot be overstated. Meet with a biostatistician to ensure your sample size calculations are correct. Work closely with the research pharmacist to ensure the medication formulation is available; decide on the manner of distribution so as not to inconvenience subjects; create a budget with an experienced manager. Seek out research coordinators often for assistance in creating case report forms, learning appropriate documentation, and crafting responses to Institutional Review Board concerns. Ask clinic personnel about arranging consent or follow-up visits around subjects’ clinic appointments. Present a draft of the protocol to your colleagues, as you will ultimately need them on board to recruit patients. And most importantly, listen to them ... all of them. Get your biases in check and write down all constructive criticism. Thoughtfully address each concern encountered to your satisfaction (and your mentor’s) and present to your village again. Rinse and repeat. Throw nothing under the rug, because if you do, it will eventually rear its head while you are in the throes of the study.

In retrospect, there were concerns raised by faculty and grant reviewers that I did not adequately address. First was the feasibility of screening, recruiting, and enrolling 80 patients during a busy clinical fellowship. While I took this criticism as a reflection of my personal commitment to the project, it was actually a call to consider the impact on clinical (and familial) responsibilities. But as I started enrolling patients, I realized there were logistic issues implied in this suggestion. I could not recruit subjects in Clinic A if I was assigned to see patients at the same time in Clinic B. Patients were not likely to come back another day for study-related discussions. Second, I designed eligibility criteria to make the data as clean as possible. Limiting the study to subjects with Crohn’s disease, in clinical and biochemical remission, without complications of their disease, who also have vitamin deficiency, may be an unrealistic recipe to recruit 80 people in a limited period of time. Finally, I designed laboratory follow-up schedules based on the pharmacokinetics of the drug alone, failing to consider the clinical milieu from which study subjects were recruited. Neglecting the fact that many patients obtain labs with their infusions, my study increased lab draw burden, heaped more patient reminders onto my plate – and more concerning – decreased overall study compliance. In short, trial design cannot be done in a vacuum or by just poring over published data. There are logistical and patient-related considerations that require early input from physicians and clinical staff in order for all the moving parts of a clinical trial to successfully work in harmony.
 

Create a timetable and follow it

Make a recruitment timetable very early on in the enrollment period. Set up biweekly meetings with mentors to discuss enrollment numbers and reflect on any unforeseen challenges. And be sure to celebrate the wins as well – not matter how small. In our study, falling behind on recruitment goals forced me to amend the stringent eligibility criteria and add additional manpower to help with reminders for laboratory follow-up and patient screening. These pivots caused study delays and cost resources. Ultimately, having a timetable forced me to take pause when it became clear I could not finish the study in the allotted time.

Know when to fold ’em

Knowing when to close a study is far easier said than done. The sunk cost fallacy says it is much harder to abandon a project after investing so many resources into it. For us, it was the recruitment timetable that gave us pause. Finishing trial accrual by the end of my advanced fellowship year was wholly unfeasible. When it became clear that nobody in the department could see it through to completion, I was propelled to terminate the study. If there is concern about termination, I suggest sending the protocol, recruitment numbers, and timeline to an outside colleague for a second, unbiased opinion. Review the already compiled data for any notable findings worthy of a smaller publication. It is said, we often learn more from our failures than our successes. The experience described herein – largely in part to my mentors, collaborators, and the patients who put their faith in me – translates to a lasting, invaluable win.

Mentor’s note

Clinical research is hard. Many trainees meet with me to “get involved” in clinical research, and the challenge as a mentor is to identify a project appropriate to the level of training and provide the infrastructure and resources to facilitate success for the motivated trainee. Trainees have various goals of their involvement in research – to foster a relationship in the hopes of receiving a strong letter of support, to facilitate getting into a competitive training program, and/or to publish. My goal as a mentor is to help my trainees reach their goals, but as a clinical researcher, I look for the trainee’s desire to engage with and learn the research process, with the ancillary potential for a letter, for acceptance to a program, or for publication.

This particular study, a randomized, controlled trial of vitamin D in patients with Crohn’s disease, involved an enormous undertaking by a very motivated trainee who took the project from its inception; to putting a thoughtful grant proposal together; to developing a full clinical trial protocol with its ancillary regulatory documents; and obtaining institutional review board approval, statistician input, pharmacy support, and buy-in from faculty and ancillary staff stakeholders. The study ultimately failed because of low enrollment – patients did not want to participate (for reasons elucidated above) – not because of poor design or execution of the myriad components of a prospective clinical trial. Low enrollment has led to the failure of many otherwise excellent studies, including several in our field of IBD.^1,2 As a mentor, it is rational to accept blame for the failure of a trainee project; how could I have better foreseen the outcome of this study? Could this have been prevented with more support, more oversight, or more “micromanagement,” to the potential detriment of fostering independence?

Ultimately, the value of clinical research to trainees is multifaceted. If the goal was a first-author publication with high clinical impact, this trial failed. But if the goal was to learn about the clinical trial process, this study was a resounding success. Ultimately, it behooves trainees and their mentors to engage in early, upfront conversations about research. What are the goals? What does success look like? What if the trial fails? By shifting the focus from the success of the project to the success of the mentorship and educational process, even failed projects are resounding successes, upon which future careers can be further developed.
 

References

1. Kan S et al. When subjects violate the research covenant: Lessons learned from a failed clinical trial of fecal microbiota transplantation. Am J Gastroenterol 2016;111:1508-10.

2. Dassopoulos T et al. Randomised clinical trial: Individualised vs.weight-based dosing of azathioprine in Crohn’s disease. Aliment Pharmacol Ther. 2014 Jan;39(2):163-75.

Dr. Cohen is an inflammatory bowel disease fellow, inflammatory bowel disease center, division of gastroenterology and hepatology, department of medicine, Cedars-Sinai Medical Center, Los Angeles. Dr. Melmed is director, inflammatory bowel disease clinical research and codirector, clinical inflammatory bowel disease, inflammatory bowel disease center, division of gastroenterology and hepatology, department of medicine, Cedars-Sinai Medical Center, Los Angeles.

As a second-year gastroenterology fellow, I designed a prospective, double-blind randomized, controlled trial for vitamin D repletion in patients with Crohn’s disease at a referral inflammatory bowel disease (IBD) center. I had the support of a dedicated research team, several mentors, and a 2-year time frame in which to complete this study. Intellectually curious and academically eager, I labored over a grant application that I did not receive. Under generous financial support from my department, I forged on and opened the trial for enrollment at the start of my advanced IBD fellowship year. However, we experienced recruitment challenges that ultimately led to the study’s premature termination. Through this journey, I gained invaluable experience that will continue to serve me – and, I hope, the reader – as I progress in my career. Below are some important insights gleaned from this experience that may benefit others interested in clinical trial design.

Know your “why” (personally and clinically)

Asked to reflect on their career path, experts tend to recount their “being in the right place at the right time” and having “good mentors.” While luck and good mentorship are necessary, I propose that doing your homework is equally as important. Before ambling down the path of an investigator-led trial, I urge a hard pause to reflect on your “why.” The personal “why” of “getting into fellowship,” “advancement in the department,” or “learning more about the principles of research,” are all valid. But I suggest a deeper dive is in order. Successful clinical trials require resources, a substantial time commitment, lots of sweat and maybe a few tears. In the ideal setting, your trial experience will serve as the foundation for a compelling personal narrative and might help launch a productive clinical research career. With stakes that high, asking the tough questions is critical.

The clinical “why” is just as critical. We press our attendings on why they used this drug or that clip, so don’t be afraid to ask whether this is a space in which others have succeeded. Or conversely, why is there such a large gap in the literature? I remember emailing the world’s expert about my topic because the published data were so murky. He had more questions than answers which, in retrospect, should have raised red flags about the ability to design a sound study. It is equally important to determine if patients are vested in the research question. A successful clinical trial hinges on subject participation, often outside their clinic visit. Patients with complex chronic diseases spend a lot of time navigating the health care system. Participating in a clinical trial needs to be meaningful to them if you want your patients to fully engage. Thoughtfully answering these questions on the front end – for yourself and the study in question – will improve both your experience and the ultimate outcome exponentially.

Identify your village (and listen to them)

Designing a clinical trial truly takes a village, and you need to identify the villagers early. As trainees, the value of mentorship is frequently underscored. But the importance of, and the nuance involved in managing, collaborating, and support cannot be overstated. Meet with a biostatistician to ensure your sample size calculations are correct. Work closely with the research pharmacist to ensure the medication formulation is available; decide on the manner of distribution so as not to inconvenience subjects; create a budget with an experienced manager. Seek out research coordinators often for assistance in creating case report forms, learning appropriate documentation, and crafting responses to Institutional Review Board concerns. Ask clinic personnel about arranging consent or follow-up visits around subjects’ clinic appointments. Present a draft of the protocol to your colleagues, as you will ultimately need them on board to recruit patients. And most importantly, listen to them ... all of them. Get your biases in check and write down all constructive criticism. Thoughtfully address each concern encountered to your satisfaction (and your mentor’s) and present to your village again. Rinse and repeat. Throw nothing under the rug, because if you do, it will eventually rear its head while you are in the throes of the study.

In retrospect, there were concerns raised by faculty and grant reviewers that I did not adequately address. First was the feasibility of screening, recruiting, and enrolling 80 patients during a busy clinical fellowship. While I took this criticism as a reflection of my personal commitment to the project, it was actually a call to consider the impact on clinical (and familial) responsibilities. But as I started enrolling patients, I realized there were logistic issues implied in this suggestion. I could not recruit subjects in Clinic A if I was assigned to see patients at the same time in Clinic B. Patients were not likely to come back another day for study-related discussions. Second, I designed eligibility criteria to make the data as clean as possible. Limiting the study to subjects with Crohn’s disease, in clinical and biochemical remission, without complications of their disease, who also have vitamin deficiency, may be an unrealistic recipe to recruit 80 people in a limited period of time. Finally, I designed laboratory follow-up schedules based on the pharmacokinetics of the drug alone, failing to consider the clinical milieu from which study subjects were recruited. Neglecting the fact that many patients obtain labs with their infusions, my study increased lab draw burden, heaped more patient reminders onto my plate – and more concerning – decreased overall study compliance. In short, trial design cannot be done in a vacuum or by just poring over published data. There are logistical and patient-related considerations that require early input from physicians and clinical staff in order for all the moving parts of a clinical trial to successfully work in harmony.
 

Create a timetable and follow it

Make a recruitment timetable very early on in the enrollment period. Set up biweekly meetings with mentors to discuss enrollment numbers and reflect on any unforeseen challenges. And be sure to celebrate the wins as well – not matter how small. In our study, falling behind on recruitment goals forced me to amend the stringent eligibility criteria and add additional manpower to help with reminders for laboratory follow-up and patient screening. These pivots caused study delays and cost resources. Ultimately, having a timetable forced me to take pause when it became clear I could not finish the study in the allotted time.

Know when to fold ’em

Knowing when to close a study is far easier said than done. The sunk cost fallacy says it is much harder to abandon a project after investing so many resources into it. For us, it was the recruitment timetable that gave us pause. Finishing trial accrual by the end of my advanced fellowship year was wholly unfeasible. When it became clear that nobody in the department could see it through to completion, I was propelled to terminate the study. If there is concern about termination, I suggest sending the protocol, recruitment numbers, and timeline to an outside colleague for a second, unbiased opinion. Review the already compiled data for any notable findings worthy of a smaller publication. It is said, we often learn more from our failures than our successes. The experience described herein – largely in part to my mentors, collaborators, and the patients who put their faith in me – translates to a lasting, invaluable win.

Mentor’s note

Clinical research is hard. Many trainees meet with me to “get involved” in clinical research, and the challenge as a mentor is to identify a project appropriate to the level of training and provide the infrastructure and resources to facilitate success for the motivated trainee. Trainees have various goals of their involvement in research – to foster a relationship in the hopes of receiving a strong letter of support, to facilitate getting into a competitive training program, and/or to publish. My goal as a mentor is to help my trainees reach their goals, but as a clinical researcher, I look for the trainee’s desire to engage with and learn the research process, with the ancillary potential for a letter, for acceptance to a program, or for publication.

This particular study, a randomized, controlled trial of vitamin D in patients with Crohn’s disease, involved an enormous undertaking by a very motivated trainee who took the project from its inception; to putting a thoughtful grant proposal together; to developing a full clinical trial protocol with its ancillary regulatory documents; and obtaining institutional review board approval, statistician input, pharmacy support, and buy-in from faculty and ancillary staff stakeholders. The study ultimately failed because of low enrollment – patients did not want to participate (for reasons elucidated above) – not because of poor design or execution of the myriad components of a prospective clinical trial. Low enrollment has led to the failure of many otherwise excellent studies, including several in our field of IBD.^1,2 As a mentor, it is rational to accept blame for the failure of a trainee project; how could I have better foreseen the outcome of this study? Could this have been prevented with more support, more oversight, or more “micromanagement,” to the potential detriment of fostering independence?

Ultimately, the value of clinical research to trainees is multifaceted. If the goal was a first-author publication with high clinical impact, this trial failed. But if the goal was to learn about the clinical trial process, this study was a resounding success. Ultimately, it behooves trainees and their mentors to engage in early, upfront conversations about research. What are the goals? What does success look like? What if the trial fails? By shifting the focus from the success of the project to the success of the mentorship and educational process, even failed projects are resounding successes, upon which future careers can be further developed.
 

References

1. Kan S et al. When subjects violate the research covenant: Lessons learned from a failed clinical trial of fecal microbiota transplantation. Am J Gastroenterol 2016;111:1508-10.

2. Dassopoulos T et al. Randomised clinical trial: Individualised vs.weight-based dosing of azathioprine in Crohn’s disease. Aliment Pharmacol Ther. 2014 Jan;39(2):163-75.

Dr. Cohen is an inflammatory bowel disease fellow, inflammatory bowel disease center, division of gastroenterology and hepatology, department of medicine, Cedars-Sinai Medical Center, Los Angeles. Dr. Melmed is director, inflammatory bowel disease clinical research and codirector, clinical inflammatory bowel disease, inflammatory bowel disease center, division of gastroenterology and hepatology, department of medicine, Cedars-Sinai Medical Center, Los Angeles.

A 38-year-old man is admitted to the hospital with a painful, swollen left leg. This was not the first instance of this kind for him. He had been admitted for the same problem 3 months earlier. During the earlier admission, he was diagnosed with cellulitis and treated with intravenous cefazolin for 4 days, then discharged on cephalexin with resolution of his swelling and pain. Today, his blood pressure is 120/70, pulse is 90, temperature is 38.2°C, his left leg is edematous from the mid-calf to the ankle, and he has erythema and warmth over the calf. His white blood cell count is 13,000, and a diagnosis of cellulitis is made. Which of the following treatments is most likely to shorten his hospital stay?

Concheiro and colleagues did a retrospective study of 122 cases of cellulitis and found tinea pedis in 33% of the cases.⁶ Muller et al. studied the importance of toe web microorganisms and erysipelas and found that the presence of interdigital tinea pedis was correlated with recurrent infection.⁷ Treatment of tinea pedis is an easily modifiable risk factor in patients with recurrent cellulitis.

Pearls: Consider adding a short course of steroids in patients with more severe erysipelas/cellulitis, as it can decrease hospital stay and IV antibiotics.

Look for tinea pedis and treat if present in patients who have erysipelas/cellulitis.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Arch Intern Med. 2008 May 26;168(10):1034-46.

2. Scand J Infect Dis 1997;29(4):377-82.

3. Scand J Infect Dis. 1998;30(2):206-7.

4. Isr Med Assoc J. 2018 Mar;20(3):137-40.

5. J Dtsch Dermatol Ges. 2004 Feb;2(2):89-95.

6. Actas Dermosifiliogr. 2009 Dec;100(10):888-94.

7. J Dtsch Dermatol Ges. 2014 Aug;12(8):691-5.

A 38-year-old man is admitted to the hospital with a painful, swollen left leg. This was not the first instance of this kind for him. He had been admitted for the same problem 3 months earlier. During the earlier admission, he was diagnosed with cellulitis and treated with intravenous cefazolin for 4 days, then discharged on cephalexin with resolution of his swelling and pain. Today, his blood pressure is 120/70, pulse is 90, temperature is 38.2°C, his left leg is edematous from the mid-calf to the ankle, and he has erythema and warmth over the calf. His white blood cell count is 13,000, and a diagnosis of cellulitis is made. Which of the following treatments is most likely to shorten his hospital stay?

Concheiro and colleagues did a retrospective study of 122 cases of cellulitis and found tinea pedis in 33% of the cases.⁶ Muller et al. studied the importance of toe web microorganisms and erysipelas and found that the presence of interdigital tinea pedis was correlated with recurrent infection.⁷ Treatment of tinea pedis is an easily modifiable risk factor in patients with recurrent cellulitis.

Pearls: Consider adding a short course of steroids in patients with more severe erysipelas/cellulitis, as it can decrease hospital stay and IV antibiotics.

Look for tinea pedis and treat if present in patients who have erysipelas/cellulitis.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Arch Intern Med. 2008 May 26;168(10):1034-46.

2. Scand J Infect Dis 1997;29(4):377-82.

3. Scand J Infect Dis. 1998;30(2):206-7.

4. Isr Med Assoc J. 2018 Mar;20(3):137-40.

5. J Dtsch Dermatol Ges. 2004 Feb;2(2):89-95.

6. Actas Dermosifiliogr. 2009 Dec;100(10):888-94.

7. J Dtsch Dermatol Ges. 2014 Aug;12(8):691-5.

A 38-year-old man is admitted to the hospital with a painful, swollen left leg. This was not the first instance of this kind for him. He had been admitted for the same problem 3 months earlier. During the earlier admission, he was diagnosed with cellulitis and treated with intravenous cefazolin for 4 days, then discharged on cephalexin with resolution of his swelling and pain. Today, his blood pressure is 120/70, pulse is 90, temperature is 38.2°C, his left leg is edematous from the mid-calf to the ankle, and he has erythema and warmth over the calf. His white blood cell count is 13,000, and a diagnosis of cellulitis is made. Which of the following treatments is most likely to shorten his hospital stay?

Concheiro and colleagues did a retrospective study of 122 cases of cellulitis and found tinea pedis in 33% of the cases.⁶ Muller et al. studied the importance of toe web microorganisms and erysipelas and found that the presence of interdigital tinea pedis was correlated with recurrent infection.⁷ Treatment of tinea pedis is an easily modifiable risk factor in patients with recurrent cellulitis.

Pearls: Consider adding a short course of steroids in patients with more severe erysipelas/cellulitis, as it can decrease hospital stay and IV antibiotics.

Look for tinea pedis and treat if present in patients who have erysipelas/cellulitis.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Arch Intern Med. 2008 May 26;168(10):1034-46.

2. Scand J Infect Dis 1997;29(4):377-82.

3. Scand J Infect Dis. 1998;30(2):206-7.

4. Isr Med Assoc J. 2018 Mar;20(3):137-40.

5. J Dtsch Dermatol Ges. 2004 Feb;2(2):89-95.

6. Actas Dermosifiliogr. 2009 Dec;100(10):888-94.

7. J Dtsch Dermatol Ges. 2014 Aug;12(8):691-5.

Starting April 1, 2019, intravenous artesunate will become the first-line treatment for malaria in the United States, following the discontinuation of quinidine, the only Food and Drug Administration–approved intravenous drug for severe malaria treatment.

Although artesunate is not approved or commercially available in the United States, it is recommended by the World Health Organization. The Centers for Disease Control and Prevention have made the drug available through an expanded use investigational new drug protocol, an FDA regulatory mechanism. Clinicians can obtain the medication through the CDC’s Malaria Hotline (770-488-7788); artesunate will be stocked at 10 quarantine stations and will be released to hospitals free of charge, according to a CDC announcement.

Clinical trials have illustrated that intravenous artesunate is safe, well tolerated, and can be administered even to infants, children, and pregnant women in the second and third trimester.

About 1,700 cases of malaria are reported in the United States per year, 300 of which are classified as severe. The CDC believes the supply of artesunate obtained will be sufficient to treat all cases of severe malaria in the country, according to a CDC press release.

[email protected]

Starting April 1, 2019, intravenous artesunate will become the first-line treatment for malaria in the United States, following the discontinuation of quinidine, the only Food and Drug Administration–approved intravenous drug for severe malaria treatment.

Although artesunate is not approved or commercially available in the United States, it is recommended by the World Health Organization. The Centers for Disease Control and Prevention have made the drug available through an expanded use investigational new drug protocol, an FDA regulatory mechanism. Clinicians can obtain the medication through the CDC’s Malaria Hotline (770-488-7788); artesunate will be stocked at 10 quarantine stations and will be released to hospitals free of charge, according to a CDC announcement.

Clinical trials have illustrated that intravenous artesunate is safe, well tolerated, and can be administered even to infants, children, and pregnant women in the second and third trimester.

About 1,700 cases of malaria are reported in the United States per year, 300 of which are classified as severe. The CDC believes the supply of artesunate obtained will be sufficient to treat all cases of severe malaria in the country, according to a CDC press release.

[email protected]

Starting April 1, 2019, intravenous artesunate will become the first-line treatment for malaria in the United States, following the discontinuation of quinidine, the only Food and Drug Administration–approved intravenous drug for severe malaria treatment.

Although artesunate is not approved or commercially available in the United States, it is recommended by the World Health Organization. The Centers for Disease Control and Prevention have made the drug available through an expanded use investigational new drug protocol, an FDA regulatory mechanism. Clinicians can obtain the medication through the CDC’s Malaria Hotline (770-488-7788); artesunate will be stocked at 10 quarantine stations and will be released to hospitals free of charge, according to a CDC announcement.

Clinical trials have illustrated that intravenous artesunate is safe, well tolerated, and can be administered even to infants, children, and pregnant women in the second and third trimester.

About 1,700 cases of malaria are reported in the United States per year, 300 of which are classified as severe. The CDC believes the supply of artesunate obtained will be sufficient to treat all cases of severe malaria in the country, according to a CDC press release.

[email protected]

Two psychiatrists are suing the American Board of Psychiatry and Neurology (ABPN) over its maintenance of certification program, contending that the board has created a monopoly over the MOC market and that its process violates antitrust laws.

The lawsuit, filed March 6 in U.S. District Court for the Northern District of Illinois, alleges that the board is illegally tying its initial certification product to its MOC product, and that ABPN is using anticompetitive actions to prevent and limit competition from new MOC providers. The suit is filed as a class action on behalf of all psychiatrists and neurologists required by ABPN to buy MOC to maintain their certifications. The plaintiffs seek damages and injunctive relief arising from the alleged violations.

In an interview, ABPN President and CEO Larry R. Faulkner, MD, said the legal challenge has no merit.

“This lawsuit will be both costly and disruptive to efforts by the ABPN to provide useful information to the physicians we serve and to foster the provision of high-quality specialty physician services,” Dr. Faulkner said. “The ABPN intends to defend itself vigorously and anticipates that, like other similar cases previously filed against the American Board of Medical Specialties and other member boards, this lawsuit will be dismissed.”

Plaintiff Emily Lazarou, MD, an Odessa, Fla.-based psychiatrist, did not return messages seeking comment. The other plaintiff, Aafaque Akhter, MD, a psychiatrist based in Norton, Mass., declined to comment at the advice of his attorneys. In a LinkedIn post, Dr. Akhter wrote that he filed the class action to put an end to MOC.

“This moneymaking operation has to be abolished,” he wrote in the post. “MOC has to go.

The 35-page complaint against the ABPN contends that the organization’s antitrust and monopolistic actions have resulted in overly burdensome conditions for physicians forced to buy MOC, and that the board’s requirements constrain the supply of psychiatrists and neurologists, thereby harming competition. The ABPN has made tens of millions of dollars in MOC revenue from psychiatrists and neurologists, the suit alleges, while physicians face countless hours away from their practice and families in order to meet MOC demands, to the physicians’ financial detriment. The challenge also asserts that ABPN’s grandfather clause – which exempts from MOC physicians who received initial certifications prior to Oct. 1, 1994 – discriminates against younger physicians, women, and persons of color, all of whom are underrepresented in the group of psychiatrists and neurologists grandfathered by ABPN.

The lawsuit details how MOC has personally and professionally affected the plaintiffs. In 2017, Dr. Lazarou, a forensic psychiatrist who also practices telepsychiatry, asked the ABPN in advance for a private room during her upcoming 10-year MOC examination. At the time, Dr. Lazarou was nursing her twin newborns and needed the private room to pump, according to the lawsuit. The suit alleges that ABPN would not make an accommodation for Dr. Lazarou to pump at the testing site; however, as a professional courtesy, board officials allowed her to travel to a test center farther away that had private rooms. Because the distance required Dr. Lazarou to be away from her newborns for an extended period, she did not take the MOC examination, and her ABPN certification lapsed, according to the suit. Because of the lapse, she is no longer able to practice telepsychiatry, which has resulted in a loss of income and to the detriment of patients who need telepsychiatric care, she claims in the lawsuit.

The ABPN lawsuit comes on the heels of a similar class action filed last year by a group of internists against the American Board of Internal Medicine (ABIM) over its MOC process. That lawsuit, filed Dec. 6 in Pennsylvania district court, contends that the ABIM is charging inflated monopoly prices for maintaining certification and that the organization is violating antitrust laws. In a motion filed March 18, attorneys for the ABIM asked the court to dismiss the suit for failure to state a valid claim. A third lawsuit that levies similar allegations against the Board of Radiology was filed in late February. All three lawsuits are being funded by the advocacy organization Practicing Physicians of America, through a GoFundMe campaign.

Richard Rosin, MD, a geriatric psychiatrist based in Vancouver, said in an interview that he welcomes and applauds the lawsuit against ABPN. He hopes that the legal challenge will put a spotlight on the board’s activities and compel administrators to answer questions about the MOC process that have gone unanswered in the past.

“At the end of the day, I hope that the case wins, because diplomates have been forced to expend their time, effort, and money on a product that has scant evidence that it improves practice,” Dr. Mathew said in an interview. “Unnecessary administrative burdens of this nature that do not improve patient care contribute to physician burnout, which is a nationwide epidemic.”

Dr. Mathew hopes to see monetary damages awarded as well as injunctive relief that would enable competition in the MOC market, he said. Such relief would prevent insurance companies and other stakeholders from only recognizing and requiring recertification with ABPN.*

“This would allow physicians the flexibility to recertify with boards like the National Board of Physicians and Surgeons,” he said.

The ABPN, meanwhile, defended its recertification, calling it a credential that is valued by patients, families, and medical organizations as an indicator that physicians have pursued “a meaningful program of lifelong learning sufficient to maintain the competence to provide quality patient care.” In recent years, the board has made improvements to its MOC requirements based on constructive feedback from diplomates and consistent with the evolving standards of the American Board of Medical Specialties, Dr. Faulkner said in the interview.

“Relevant options have been provided for the documentation of self-assessment and performance improvement, and they have been well received by diplomates,” he said. “The ABPN is also in the process of implementing an optional, article-based Pilot Project as an alternative to its secure continuing certification examination. Almost 15,000 ABPN diplomates have enrolled to date in the Pilot Project, and initial feedback from those diplomates has also been very favorable.”

*Correction, 4/5/19: Due to an editing error, an earlier version of this article omitted the word "only" from this sentence.

[email protected]

Two psychiatrists are suing the American Board of Psychiatry and Neurology (ABPN) over its maintenance of certification program, contending that the board has created a monopoly over the MOC market and that its process violates antitrust laws.

The lawsuit, filed March 6 in U.S. District Court for the Northern District of Illinois, alleges that the board is illegally tying its initial certification product to its MOC product, and that ABPN is using anticompetitive actions to prevent and limit competition from new MOC providers. The suit is filed as a class action on behalf of all psychiatrists and neurologists required by ABPN to buy MOC to maintain their certifications. The plaintiffs seek damages and injunctive relief arising from the alleged violations.

In an interview, ABPN President and CEO Larry R. Faulkner, MD, said the legal challenge has no merit.

“This lawsuit will be both costly and disruptive to efforts by the ABPN to provide useful information to the physicians we serve and to foster the provision of high-quality specialty physician services,” Dr. Faulkner said. “The ABPN intends to defend itself vigorously and anticipates that, like other similar cases previously filed against the American Board of Medical Specialties and other member boards, this lawsuit will be dismissed.”

Plaintiff Emily Lazarou, MD, an Odessa, Fla.-based psychiatrist, did not return messages seeking comment. The other plaintiff, Aafaque Akhter, MD, a psychiatrist based in Norton, Mass., declined to comment at the advice of his attorneys. In a LinkedIn post, Dr. Akhter wrote that he filed the class action to put an end to MOC.

“This moneymaking operation has to be abolished,” he wrote in the post. “MOC has to go.

The 35-page complaint against the ABPN contends that the organization’s antitrust and monopolistic actions have resulted in overly burdensome conditions for physicians forced to buy MOC, and that the board’s requirements constrain the supply of psychiatrists and neurologists, thereby harming competition. The ABPN has made tens of millions of dollars in MOC revenue from psychiatrists and neurologists, the suit alleges, while physicians face countless hours away from their practice and families in order to meet MOC demands, to the physicians’ financial detriment. The challenge also asserts that ABPN’s grandfather clause – which exempts from MOC physicians who received initial certifications prior to Oct. 1, 1994 – discriminates against younger physicians, women, and persons of color, all of whom are underrepresented in the group of psychiatrists and neurologists grandfathered by ABPN.

The lawsuit details how MOC has personally and professionally affected the plaintiffs. In 2017, Dr. Lazarou, a forensic psychiatrist who also practices telepsychiatry, asked the ABPN in advance for a private room during her upcoming 10-year MOC examination. At the time, Dr. Lazarou was nursing her twin newborns and needed the private room to pump, according to the lawsuit. The suit alleges that ABPN would not make an accommodation for Dr. Lazarou to pump at the testing site; however, as a professional courtesy, board officials allowed her to travel to a test center farther away that had private rooms. Because the distance required Dr. Lazarou to be away from her newborns for an extended period, she did not take the MOC examination, and her ABPN certification lapsed, according to the suit. Because of the lapse, she is no longer able to practice telepsychiatry, which has resulted in a loss of income and to the detriment of patients who need telepsychiatric care, she claims in the lawsuit.

The ABPN lawsuit comes on the heels of a similar class action filed last year by a group of internists against the American Board of Internal Medicine (ABIM) over its MOC process. That lawsuit, filed Dec. 6 in Pennsylvania district court, contends that the ABIM is charging inflated monopoly prices for maintaining certification and that the organization is violating antitrust laws. In a motion filed March 18, attorneys for the ABIM asked the court to dismiss the suit for failure to state a valid claim. A third lawsuit that levies similar allegations against the Board of Radiology was filed in late February. All three lawsuits are being funded by the advocacy organization Practicing Physicians of America, through a GoFundMe campaign.

Richard Rosin, MD, a geriatric psychiatrist based in Vancouver, said in an interview that he welcomes and applauds the lawsuit against ABPN. He hopes that the legal challenge will put a spotlight on the board’s activities and compel administrators to answer questions about the MOC process that have gone unanswered in the past.

“At the end of the day, I hope that the case wins, because diplomates have been forced to expend their time, effort, and money on a product that has scant evidence that it improves practice,” Dr. Mathew said in an interview. “Unnecessary administrative burdens of this nature that do not improve patient care contribute to physician burnout, which is a nationwide epidemic.”

Dr. Mathew hopes to see monetary damages awarded as well as injunctive relief that would enable competition in the MOC market, he said. Such relief would prevent insurance companies and other stakeholders from only recognizing and requiring recertification with ABPN.*

“This would allow physicians the flexibility to recertify with boards like the National Board of Physicians and Surgeons,” he said.

The ABPN, meanwhile, defended its recertification, calling it a credential that is valued by patients, families, and medical organizations as an indicator that physicians have pursued “a meaningful program of lifelong learning sufficient to maintain the competence to provide quality patient care.” In recent years, the board has made improvements to its MOC requirements based on constructive feedback from diplomates and consistent with the evolving standards of the American Board of Medical Specialties, Dr. Faulkner said in the interview.

“Relevant options have been provided for the documentation of self-assessment and performance improvement, and they have been well received by diplomates,” he said. “The ABPN is also in the process of implementing an optional, article-based Pilot Project as an alternative to its secure continuing certification examination. Almost 15,000 ABPN diplomates have enrolled to date in the Pilot Project, and initial feedback from those diplomates has also been very favorable.”

*Correction, 4/5/19: Due to an editing error, an earlier version of this article omitted the word "only" from this sentence.

[email protected]

Two psychiatrists are suing the American Board of Psychiatry and Neurology (ABPN) over its maintenance of certification program, contending that the board has created a monopoly over the MOC market and that its process violates antitrust laws.

The lawsuit, filed March 6 in U.S. District Court for the Northern District of Illinois, alleges that the board is illegally tying its initial certification product to its MOC product, and that ABPN is using anticompetitive actions to prevent and limit competition from new MOC providers. The suit is filed as a class action on behalf of all psychiatrists and neurologists required by ABPN to buy MOC to maintain their certifications. The plaintiffs seek damages and injunctive relief arising from the alleged violations.

In an interview, ABPN President and CEO Larry R. Faulkner, MD, said the legal challenge has no merit.

“This lawsuit will be both costly and disruptive to efforts by the ABPN to provide useful information to the physicians we serve and to foster the provision of high-quality specialty physician services,” Dr. Faulkner said. “The ABPN intends to defend itself vigorously and anticipates that, like other similar cases previously filed against the American Board of Medical Specialties and other member boards, this lawsuit will be dismissed.”

Plaintiff Emily Lazarou, MD, an Odessa, Fla.-based psychiatrist, did not return messages seeking comment. The other plaintiff, Aafaque Akhter, MD, a psychiatrist based in Norton, Mass., declined to comment at the advice of his attorneys. In a LinkedIn post, Dr. Akhter wrote that he filed the class action to put an end to MOC.

“This moneymaking operation has to be abolished,” he wrote in the post. “MOC has to go.

The 35-page complaint against the ABPN contends that the organization’s antitrust and monopolistic actions have resulted in overly burdensome conditions for physicians forced to buy MOC, and that the board’s requirements constrain the supply of psychiatrists and neurologists, thereby harming competition. The ABPN has made tens of millions of dollars in MOC revenue from psychiatrists and neurologists, the suit alleges, while physicians face countless hours away from their practice and families in order to meet MOC demands, to the physicians’ financial detriment. The challenge also asserts that ABPN’s grandfather clause – which exempts from MOC physicians who received initial certifications prior to Oct. 1, 1994 – discriminates against younger physicians, women, and persons of color, all of whom are underrepresented in the group of psychiatrists and neurologists grandfathered by ABPN.

The lawsuit details how MOC has personally and professionally affected the plaintiffs. In 2017, Dr. Lazarou, a forensic psychiatrist who also practices telepsychiatry, asked the ABPN in advance for a private room during her upcoming 10-year MOC examination. At the time, Dr. Lazarou was nursing her twin newborns and needed the private room to pump, according to the lawsuit. The suit alleges that ABPN would not make an accommodation for Dr. Lazarou to pump at the testing site; however, as a professional courtesy, board officials allowed her to travel to a test center farther away that had private rooms. Because the distance required Dr. Lazarou to be away from her newborns for an extended period, she did not take the MOC examination, and her ABPN certification lapsed, according to the suit. Because of the lapse, she is no longer able to practice telepsychiatry, which has resulted in a loss of income and to the detriment of patients who need telepsychiatric care, she claims in the lawsuit.

The ABPN lawsuit comes on the heels of a similar class action filed last year by a group of internists against the American Board of Internal Medicine (ABIM) over its MOC process. That lawsuit, filed Dec. 6 in Pennsylvania district court, contends that the ABIM is charging inflated monopoly prices for maintaining certification and that the organization is violating antitrust laws. In a motion filed March 18, attorneys for the ABIM asked the court to dismiss the suit for failure to state a valid claim. A third lawsuit that levies similar allegations against the Board of Radiology was filed in late February. All three lawsuits are being funded by the advocacy organization Practicing Physicians of America, through a GoFundMe campaign.

Richard Rosin, MD, a geriatric psychiatrist based in Vancouver, said in an interview that he welcomes and applauds the lawsuit against ABPN. He hopes that the legal challenge will put a spotlight on the board’s activities and compel administrators to answer questions about the MOC process that have gone unanswered in the past.

“At the end of the day, I hope that the case wins, because diplomates have been forced to expend their time, effort, and money on a product that has scant evidence that it improves practice,” Dr. Mathew said in an interview. “Unnecessary administrative burdens of this nature that do not improve patient care contribute to physician burnout, which is a nationwide epidemic.”

Dr. Mathew hopes to see monetary damages awarded as well as injunctive relief that would enable competition in the MOC market, he said. Such relief would prevent insurance companies and other stakeholders from only recognizing and requiring recertification with ABPN.*

“This would allow physicians the flexibility to recertify with boards like the National Board of Physicians and Surgeons,” he said.

The ABPN, meanwhile, defended its recertification, calling it a credential that is valued by patients, families, and medical organizations as an indicator that physicians have pursued “a meaningful program of lifelong learning sufficient to maintain the competence to provide quality patient care.” In recent years, the board has made improvements to its MOC requirements based on constructive feedback from diplomates and consistent with the evolving standards of the American Board of Medical Specialties, Dr. Faulkner said in the interview.

“Relevant options have been provided for the documentation of self-assessment and performance improvement, and they have been well received by diplomates,” he said. “The ABPN is also in the process of implementing an optional, article-based Pilot Project as an alternative to its secure continuing certification examination. Almost 15,000 ABPN diplomates have enrolled to date in the Pilot Project, and initial feedback from those diplomates has also been very favorable.”

*Correction, 4/5/19: Due to an editing error, an earlier version of this article omitted the word "only" from this sentence.

[email protected]