Mixed Topics

MILAN – Targeting the Janus kinase (JAK) 1 and 2 pathways in vitiligo resulted in significant reduction of facial depigmentation after 24 weeks of treatment, in a phase 2b trial of topical ruxolitinib cream.

Kari Oakes/MDedge News

With all four doses of ruxolitinib in the cream formulation evaluated, significantly more patients with vitiligo had at least 50% facial repigmentation, compared with vehicle alone, said David Rosmarin, MD, speaking in a late-breaking abstracts session at the World Congress of Dermatology.

The highest response rate was seen with a higher dose: Among patients receiving ruxolitinib cream 1.5% once daily, 50% met the 50% clearing mark at 24 weeks, as did 45.5% of those with twice-daily 1.5% dosing of the 1.5% formulation. At 24 weeks, 3.1% of those receiving vehicle had 50% facial vitiligo resolution (P less than .0001, compared with vehicle for both doses).

Vitiligo affects about 3,000,000 people in the United States, and it is a plausible treatment target for the JAK inhibitor ruxolitinib, explained Dr. Rosmarin, a dermatologist at Tufts University, Boston. “Interferon-gamma, signaling through JAK1 and JAK2, is central to the pathogenesis of vitiligo,” he said. “Ruxolitinib is a potent inhibitor of JAK1 and JAK2, so it made sense to investigate it as a treatment for vitiligo.”

The 24-month randomized, double-blind, vehicle-controlled phase 2 study of ruxolitinib cream for vitiligo compared the vehicle to four different concentrations of ruxolitinib during the first phase of the study. For the first 24 weeks, patients were randomized to receive vehicle twice daily, or various doses of ruxolitinib ranging from 0.15% once daily to 1.5% twice daily.

At this point, the study’s primary endpoint was assessed, with investigators comparing the proportion of patients treated with ruxolitinib who had at least 50% improvement in facial repigmentation from baseline on the Facial Vitiligo Area Scoring Index (F-VASI50) compared with those who received vehicle. A secondary endpoint, also assessed at week 24, was the proportion of patients who were clear, or almost clear, of facial vitiligo; safety and tolerability were also assessed.

In addition to the F-VASI50 measure, Dr. Rosmarin and his coinvestigators also tracked 75% facial clearing (F-VASI75). Here, the 1.5% twice daily regimen topped the others, with 30% of those receiving that dose achieving F-VASI75, compared with almost 10%-17% of those on other doses.

Using another measure, More than one-third of patients using ruxolitinib (35.3%) had clear (no signs of vitiligo) or almost clear (only specks of depigmentation) facial skin at week 24, according to a clinician assessment tool. No patients on placebo had clear or almost clear facial skin at that point. “It is my hope that with continued use beyond week 24, more patients will meet this very stringent endpoint,” Dr. Rosmarin said.

The safety profile was good, with no serious treatment-related adverse events, and no application site reactions that reached clinical significance, although numerically more patients reported acne with ruxolitinib than with vehicle alone.


In the trial, patients aged 18-75 years with vitiligo were eligible if they had facial depigmentation that constituted at least half of their body surface area (BSA), as well as depigmentation of at least 3% of BSA on nonfacial areas. Patients were excluded if they had another dermatologic disease, infection, prior JAK inhibitor therapy, or recent use of biologic or experimental drugs, laser or light-based treatments, or immunomodulators. Of the 157 patients who were randomized, 18 patients (11.5%) had discontinued treatment by week 24, with 3 patients stopping for adverse events, 3 for protocol deviation or noncompliance, and 10 withdrawals. Two patients were lost to follow-up; all patients were included in analysis of the primary and secondary endpoints.

In the second year of the study, investigators rerandomized patients who had been receiving vehicle to an active arm of the study, and patients who had less than 25% improvement on a facial vitiligo scoring scale were rerandomized to one of the different doses. Twenty-eight weeks after rerandomization, all participants were given the opportunity to participate in a year-long open-label extension, receiving 1.5% ruxolitinib cream twice daily. Phototherapy was allowed in the extension arm, but not in the first year of the study.

Data beyond 24 weeks have not yet been reported, and the 2-year study plan acknowledged that “repigmentation takes a while,” Dr. Rosmarin said. He added that patients were allowed to use the study drug on body vitiligo as well, and many saw improvement there, although these results weren’t tracked in the study. “This isn’t a drug that’s meant just for the face,” he said.

Dr. Rosmarin and his coauthors reported financial arrangements with several pharmaceutical companies, including Incyte, which funded the study. An oral formulation of ruxolitinib (Jakafi), marketed by Incyte, was approved by the Food and Drug Administration in 2011, for myelofibrosis, and was recently approved for steroid-refractory acute graft-versus-host disease in adults and children aged 12 years and older.

[email protected]

MILAN – Targeting the Janus kinase (JAK) 1 and 2 pathways in vitiligo resulted in significant reduction of facial depigmentation after 24 weeks of treatment, in a phase 2b trial of topical ruxolitinib cream.

Kari Oakes/MDedge News

With all four doses of ruxolitinib in the cream formulation evaluated, significantly more patients with vitiligo had at least 50% facial repigmentation, compared with vehicle alone, said David Rosmarin, MD, speaking in a late-breaking abstracts session at the World Congress of Dermatology.

The highest response rate was seen with a higher dose: Among patients receiving ruxolitinib cream 1.5% once daily, 50% met the 50% clearing mark at 24 weeks, as did 45.5% of those with twice-daily 1.5% dosing of the 1.5% formulation. At 24 weeks, 3.1% of those receiving vehicle had 50% facial vitiligo resolution (P less than .0001, compared with vehicle for both doses).

Vitiligo affects about 3,000,000 people in the United States, and it is a plausible treatment target for the JAK inhibitor ruxolitinib, explained Dr. Rosmarin, a dermatologist at Tufts University, Boston. “Interferon-gamma, signaling through JAK1 and JAK2, is central to the pathogenesis of vitiligo,” he said. “Ruxolitinib is a potent inhibitor of JAK1 and JAK2, so it made sense to investigate it as a treatment for vitiligo.”

The 24-month randomized, double-blind, vehicle-controlled phase 2 study of ruxolitinib cream for vitiligo compared the vehicle to four different concentrations of ruxolitinib during the first phase of the study. For the first 24 weeks, patients were randomized to receive vehicle twice daily, or various doses of ruxolitinib ranging from 0.15% once daily to 1.5% twice daily.

At this point, the study’s primary endpoint was assessed, with investigators comparing the proportion of patients treated with ruxolitinib who had at least 50% improvement in facial repigmentation from baseline on the Facial Vitiligo Area Scoring Index (F-VASI50) compared with those who received vehicle. A secondary endpoint, also assessed at week 24, was the proportion of patients who were clear, or almost clear, of facial vitiligo; safety and tolerability were also assessed.

In addition to the F-VASI50 measure, Dr. Rosmarin and his coinvestigators also tracked 75% facial clearing (F-VASI75). Here, the 1.5% twice daily regimen topped the others, with 30% of those receiving that dose achieving F-VASI75, compared with almost 10%-17% of those on other doses.

Using another measure, More than one-third of patients using ruxolitinib (35.3%) had clear (no signs of vitiligo) or almost clear (only specks of depigmentation) facial skin at week 24, according to a clinician assessment tool. No patients on placebo had clear or almost clear facial skin at that point. “It is my hope that with continued use beyond week 24, more patients will meet this very stringent endpoint,” Dr. Rosmarin said.

The safety profile was good, with no serious treatment-related adverse events, and no application site reactions that reached clinical significance, although numerically more patients reported acne with ruxolitinib than with vehicle alone.


In the trial, patients aged 18-75 years with vitiligo were eligible if they had facial depigmentation that constituted at least half of their body surface area (BSA), as well as depigmentation of at least 3% of BSA on nonfacial areas. Patients were excluded if they had another dermatologic disease, infection, prior JAK inhibitor therapy, or recent use of biologic or experimental drugs, laser or light-based treatments, or immunomodulators. Of the 157 patients who were randomized, 18 patients (11.5%) had discontinued treatment by week 24, with 3 patients stopping for adverse events, 3 for protocol deviation or noncompliance, and 10 withdrawals. Two patients were lost to follow-up; all patients were included in analysis of the primary and secondary endpoints.

In the second year of the study, investigators rerandomized patients who had been receiving vehicle to an active arm of the study, and patients who had less than 25% improvement on a facial vitiligo scoring scale were rerandomized to one of the different doses. Twenty-eight weeks after rerandomization, all participants were given the opportunity to participate in a year-long open-label extension, receiving 1.5% ruxolitinib cream twice daily. Phototherapy was allowed in the extension arm, but not in the first year of the study.

Data beyond 24 weeks have not yet been reported, and the 2-year study plan acknowledged that “repigmentation takes a while,” Dr. Rosmarin said. He added that patients were allowed to use the study drug on body vitiligo as well, and many saw improvement there, although these results weren’t tracked in the study. “This isn’t a drug that’s meant just for the face,” he said.

Dr. Rosmarin and his coauthors reported financial arrangements with several pharmaceutical companies, including Incyte, which funded the study. An oral formulation of ruxolitinib (Jakafi), marketed by Incyte, was approved by the Food and Drug Administration in 2011, for myelofibrosis, and was recently approved for steroid-refractory acute graft-versus-host disease in adults and children aged 12 years and older.

[email protected]

MILAN – Targeting the Janus kinase (JAK) 1 and 2 pathways in vitiligo resulted in significant reduction of facial depigmentation after 24 weeks of treatment, in a phase 2b trial of topical ruxolitinib cream.

Kari Oakes/MDedge News

With all four doses of ruxolitinib in the cream formulation evaluated, significantly more patients with vitiligo had at least 50% facial repigmentation, compared with vehicle alone, said David Rosmarin, MD, speaking in a late-breaking abstracts session at the World Congress of Dermatology.

The highest response rate was seen with a higher dose: Among patients receiving ruxolitinib cream 1.5% once daily, 50% met the 50% clearing mark at 24 weeks, as did 45.5% of those with twice-daily 1.5% dosing of the 1.5% formulation. At 24 weeks, 3.1% of those receiving vehicle had 50% facial vitiligo resolution (P less than .0001, compared with vehicle for both doses).

Vitiligo affects about 3,000,000 people in the United States, and it is a plausible treatment target for the JAK inhibitor ruxolitinib, explained Dr. Rosmarin, a dermatologist at Tufts University, Boston. “Interferon-gamma, signaling through JAK1 and JAK2, is central to the pathogenesis of vitiligo,” he said. “Ruxolitinib is a potent inhibitor of JAK1 and JAK2, so it made sense to investigate it as a treatment for vitiligo.”

The 24-month randomized, double-blind, vehicle-controlled phase 2 study of ruxolitinib cream for vitiligo compared the vehicle to four different concentrations of ruxolitinib during the first phase of the study. For the first 24 weeks, patients were randomized to receive vehicle twice daily, or various doses of ruxolitinib ranging from 0.15% once daily to 1.5% twice daily.

At this point, the study’s primary endpoint was assessed, with investigators comparing the proportion of patients treated with ruxolitinib who had at least 50% improvement in facial repigmentation from baseline on the Facial Vitiligo Area Scoring Index (F-VASI50) compared with those who received vehicle. A secondary endpoint, also assessed at week 24, was the proportion of patients who were clear, or almost clear, of facial vitiligo; safety and tolerability were also assessed.

In addition to the F-VASI50 measure, Dr. Rosmarin and his coinvestigators also tracked 75% facial clearing (F-VASI75). Here, the 1.5% twice daily regimen topped the others, with 30% of those receiving that dose achieving F-VASI75, compared with almost 10%-17% of those on other doses.

Using another measure, More than one-third of patients using ruxolitinib (35.3%) had clear (no signs of vitiligo) or almost clear (only specks of depigmentation) facial skin at week 24, according to a clinician assessment tool. No patients on placebo had clear or almost clear facial skin at that point. “It is my hope that with continued use beyond week 24, more patients will meet this very stringent endpoint,” Dr. Rosmarin said.

The safety profile was good, with no serious treatment-related adverse events, and no application site reactions that reached clinical significance, although numerically more patients reported acne with ruxolitinib than with vehicle alone.


In the trial, patients aged 18-75 years with vitiligo were eligible if they had facial depigmentation that constituted at least half of their body surface area (BSA), as well as depigmentation of at least 3% of BSA on nonfacial areas. Patients were excluded if they had another dermatologic disease, infection, prior JAK inhibitor therapy, or recent use of biologic or experimental drugs, laser or light-based treatments, or immunomodulators. Of the 157 patients who were randomized, 18 patients (11.5%) had discontinued treatment by week 24, with 3 patients stopping for adverse events, 3 for protocol deviation or noncompliance, and 10 withdrawals. Two patients were lost to follow-up; all patients were included in analysis of the primary and secondary endpoints.

In the second year of the study, investigators rerandomized patients who had been receiving vehicle to an active arm of the study, and patients who had less than 25% improvement on a facial vitiligo scoring scale were rerandomized to one of the different doses. Twenty-eight weeks after rerandomization, all participants were given the opportunity to participate in a year-long open-label extension, receiving 1.5% ruxolitinib cream twice daily. Phototherapy was allowed in the extension arm, but not in the first year of the study.

Data beyond 24 weeks have not yet been reported, and the 2-year study plan acknowledged that “repigmentation takes a while,” Dr. Rosmarin said. He added that patients were allowed to use the study drug on body vitiligo as well, and many saw improvement there, although these results weren’t tracked in the study. “This isn’t a drug that’s meant just for the face,” he said.

Dr. Rosmarin and his coauthors reported financial arrangements with several pharmaceutical companies, including Incyte, which funded the study. An oral formulation of ruxolitinib (Jakafi), marketed by Incyte, was approved by the Food and Drug Administration in 2011, for myelofibrosis, and was recently approved for steroid-refractory acute graft-versus-host disease in adults and children aged 12 years and older.

[email protected]

To the Editor:

Granuloma annulare (GA) is a common dermatosis that usually presents with dermal papules and annular plaques in a symmetric distribution.¹ The etiology is unknown, but a delayed-type hypersensitivity reaction is the favored pathogenesis. Several systemic associations have been reported with generalized GA including diabetes mellitus, hyperlipidemia, autoimmune thyroiditis, rheumatoid arthritis, and lymphoproliferative malignancies, as well as other malignancies and viral infections such as human immunodeficiency virus and hepatitis C. Localized GA often is self-limiting, but generalized disease can be chronic and progressive. Although asymptomatic in most cases, the lesions can be cosmetically bothersome, and many patients desire treatment. There are few well-controlled studies of treatment, and most are limited to case reports and series. A review of GA treatment noted only 3 randomized studies: 2 relating to photodynamic therapy and 1 to cryosurgery. Well-accepted therapies, such as topical and intralesional corticosteroids, antimalarials, immunosuppressants, antibiotics, and phototherapy, are substantiated by lesser-quality evidence.¹ Phototherapy has been studied for the treatment of GA and other disorders with altered dermal matrix deposition for which there are limited effective treatment options. UV irradiation promotes degradation of structural components of the dermis and inhibition of collagen production.² Granuloma annulare generally is resistant to therapy. We report a case of generalized GA of long duration that responded well to phototherapy with narrowband UVB (NB-UVB).

A 60-year-old woman presented with generalized GA of 4 years’ duration that was confirmed on biopsy on 2 occasions (Figure 1). The lesions were asymptomatic but disfiguring and consisted of extensive pink, thin, annular plaques and papules on the torso, arms, and legs (Figure 2A). Apart from mild depression for which she was being treated with paroxetine and trazodone, she was otherwise healthy without evidence of thyroid disease, hyperlipidemia, or diabetes mellitus. Prior treatments for GA had included tapering courses of prednisone (up to 30 mg/d, tapered by 5 mg every 4 days) and betamethasone dipropionate cream 0.05%. She was started on NB-UVB therapy 5 times weekly in incremental doses with no adjuvant therapy. After 100 treatments, there was notable improvement with lesions becoming paler and flatter, with some involuting completely (Figure 2B). The frequency of treatment was reduced to 3 times weekly with continued improvement. An NB-UVB device was used containing 48 TL 100W/01-FS72 lamps with a mean irradiance of 2.9 mW/cm². Her starting dose was 90 mJ/cm². The cumulative dose after 100 treatments was 35,600 mJ/cm². Apart from occasional mild erythema, there were no adverse effects.

To the Editor:

Granuloma annulare (GA) is a common dermatosis that usually presents with dermal papules and annular plaques in a symmetric distribution.¹ The etiology is unknown, but a delayed-type hypersensitivity reaction is the favored pathogenesis. Several systemic associations have been reported with generalized GA including diabetes mellitus, hyperlipidemia, autoimmune thyroiditis, rheumatoid arthritis, and lymphoproliferative malignancies, as well as other malignancies and viral infections such as human immunodeficiency virus and hepatitis C. Localized GA often is self-limiting, but generalized disease can be chronic and progressive. Although asymptomatic in most cases, the lesions can be cosmetically bothersome, and many patients desire treatment. There are few well-controlled studies of treatment, and most are limited to case reports and series. A review of GA treatment noted only 3 randomized studies: 2 relating to photodynamic therapy and 1 to cryosurgery. Well-accepted therapies, such as topical and intralesional corticosteroids, antimalarials, immunosuppressants, antibiotics, and phototherapy, are substantiated by lesser-quality evidence.¹ Phototherapy has been studied for the treatment of GA and other disorders with altered dermal matrix deposition for which there are limited effective treatment options. UV irradiation promotes degradation of structural components of the dermis and inhibition of collagen production.² Granuloma annulare generally is resistant to therapy. We report a case of generalized GA of long duration that responded well to phototherapy with narrowband UVB (NB-UVB).

A 60-year-old woman presented with generalized GA of 4 years’ duration that was confirmed on biopsy on 2 occasions (Figure 1). The lesions were asymptomatic but disfiguring and consisted of extensive pink, thin, annular plaques and papules on the torso, arms, and legs (Figure 2A). Apart from mild depression for which she was being treated with paroxetine and trazodone, she was otherwise healthy without evidence of thyroid disease, hyperlipidemia, or diabetes mellitus. Prior treatments for GA had included tapering courses of prednisone (up to 30 mg/d, tapered by 5 mg every 4 days) and betamethasone dipropionate cream 0.05%. She was started on NB-UVB therapy 5 times weekly in incremental doses with no adjuvant therapy. After 100 treatments, there was notable improvement with lesions becoming paler and flatter, with some involuting completely (Figure 2B). The frequency of treatment was reduced to 3 times weekly with continued improvement. An NB-UVB device was used containing 48 TL 100W/01-FS72 lamps with a mean irradiance of 2.9 mW/cm². Her starting dose was 90 mJ/cm². The cumulative dose after 100 treatments was 35,600 mJ/cm². Apart from occasional mild erythema, there were no adverse effects.

To the Editor:

Granuloma annulare (GA) is a common dermatosis that usually presents with dermal papules and annular plaques in a symmetric distribution.¹ The etiology is unknown, but a delayed-type hypersensitivity reaction is the favored pathogenesis. Several systemic associations have been reported with generalized GA including diabetes mellitus, hyperlipidemia, autoimmune thyroiditis, rheumatoid arthritis, and lymphoproliferative malignancies, as well as other malignancies and viral infections such as human immunodeficiency virus and hepatitis C. Localized GA often is self-limiting, but generalized disease can be chronic and progressive. Although asymptomatic in most cases, the lesions can be cosmetically bothersome, and many patients desire treatment. There are few well-controlled studies of treatment, and most are limited to case reports and series. A review of GA treatment noted only 3 randomized studies: 2 relating to photodynamic therapy and 1 to cryosurgery. Well-accepted therapies, such as topical and intralesional corticosteroids, antimalarials, immunosuppressants, antibiotics, and phototherapy, are substantiated by lesser-quality evidence.¹ Phototherapy has been studied for the treatment of GA and other disorders with altered dermal matrix deposition for which there are limited effective treatment options. UV irradiation promotes degradation of structural components of the dermis and inhibition of collagen production.² Granuloma annulare generally is resistant to therapy. We report a case of generalized GA of long duration that responded well to phototherapy with narrowband UVB (NB-UVB).

A 60-year-old woman presented with generalized GA of 4 years’ duration that was confirmed on biopsy on 2 occasions (Figure 1). The lesions were asymptomatic but disfiguring and consisted of extensive pink, thin, annular plaques and papules on the torso, arms, and legs (Figure 2A). Apart from mild depression for which she was being treated with paroxetine and trazodone, she was otherwise healthy without evidence of thyroid disease, hyperlipidemia, or diabetes mellitus. Prior treatments for GA had included tapering courses of prednisone (up to 30 mg/d, tapered by 5 mg every 4 days) and betamethasone dipropionate cream 0.05%. She was started on NB-UVB therapy 5 times weekly in incremental doses with no adjuvant therapy. After 100 treatments, there was notable improvement with lesions becoming paler and flatter, with some involuting completely (Figure 2B). The frequency of treatment was reduced to 3 times weekly with continued improvement. An NB-UVB device was used containing 48 TL 100W/01-FS72 lamps with a mean irradiance of 2.9 mW/cm². Her starting dose was 90 mJ/cm². The cumulative dose after 100 treatments was 35,600 mJ/cm². Apart from occasional mild erythema, there were no adverse effects.

After 20 years on the rise, new cases of diagnosed diabetes mellitus (DM) in the US have declined by 35%, from 1.7 million in 2008 to 1.3 million in 2017, according to CDC researchers. Not only that: The number of people living with diagnosed DM in the US has remained stable for the past 8 years.

The findings represent the longest decline in new DM cases and the longest sustained plateau in existing cases. Between 1990 and 2009, the number of people living with diagnosed diabetes (DD) rose 4.4% per year, peaked at 8.2 per 100 adults, then leveled off at 8 per 100 in 2017. The trends were similar across age groups, racial and ethnic groups, and genders.

In part, the plateau may be due to the fact that people with DM are living longer, the researchers suggest, pointing to recent reports of a decline in cardiovascular and all-cause mortality in adults with DD.

But maybe the work to “stem the tide of type 2 diabetes” is finally having an effect, says Ann Albright, PhD, director of the CDC Division of Diabetes Translation. She stresses the importance of “putting science-proven programs into action,” citing the National Diabetes Prevention Program as a prime example. But she adds, “We must also increase access to affordable, healthier foods, and safe places to be active.”

The news about the decrease in new diabetes cases comes simultaneously with findings from the Restoring Insulin Secretion (RISE) Adult and Pediatric Medication Studies, which found that type 2 diabetes mellitus (T2DM) progression slows during treatment but resumes after treatment stops.

The research, funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was aimed at finding ways to preserve β-cell function. The adult study randomly assigned participants aged 20 to 65 years to receive long-acting insulin (glargine) for 3 months, followed by metformin for 9 months; liraglutide with metformin for 12 months; metformin alone for 12 months; or placebo. Participants’ β-cell function and blood glucose control improved on the treatments, with those in the liraglutide/metformin group showing the most improvement. But the improvements did not persist after treatment ended. “[T]reatment options were equally effective while people were actively on them,” says study chair Dr. Steven Kahn, from the VA Puget Sound Health Care System. “But people need to stay on treatment to maintain the benefits.”

The youth study (participants aged 10-19 years) study compared 3 months of insulin glargine, followed by metformin for 9 months, to metformin alone for 12 months. (Insulin glargine and metformin are the only FDA-approved drugs for young people with T2D )  β-cell function declined in the 2 pediatric treatment groups and even worsened after treatment ended. The studies support earlier evidence that T2DM affects young people differently and more aggressively than it does in adults, NIDDK Director Dr. Griffin Rodgers says.

Other research news is brighter for people at risk for type 1 diabetes mellitus (T1DM): An NIH-funded study found that treatment with teplizumab, an anti-CD3 monoclonal antibody, delayed clinical T1DM by ≥ 2 years.

Previous research had found that teplizumab slows the loss of β cells in people with recent-onset clinical T1DM, but the drug had not been tested in people without clinical disease. The researchers wanted to see whether early intervention would have a benefit for people at high risk. They compared a 14-day course of teplizumab with placebo in 76 participants aged 8 to 49 years who were relatives of people with T1DM, had at ≥ 2 types of DM-related autoantibodies, and had abnormal glucose tolerance.

During the trial, 72% of people on placebo developed clinical DM compared with 43% of those in the treatment group. The median time for the control participants to develop DM was just over 24 months vs 48 months in the teplizumab group. The effects of the drug were greatest in the first year after it was given, when 41% of the participants—mainly in the placebo group—developed clinical diabetes.

At-risk children and adolescents are known to progress to T1DM faster than adults, the researchers note. They say faster progression is associated with a highly active immune system, which may explain the impact of immune system-modulating drugs like teplizumab.

The study “illustrates how decades of research on the biology of T1D can lead to promising treatments that have a real impact on people’s lives,” NIDDK Director Rodgers says.

But the T1DM and T2DM studies, although highlighting areas of effectiveness, also underscore the continued need for new approaches to prevent and treat DM in young people.

Although the drop in new cases of T2DM are still unclear, the CDC researchers suggest that they are driven in part by increased awareness of DM prevention, changes in diet, changes in physical activity, and changes in diagnostic and screening practices. In other words, prevention also remains an urgent need.

After 20 years on the rise, new cases of diagnosed diabetes mellitus (DM) in the US have declined by 35%, from 1.7 million in 2008 to 1.3 million in 2017, according to CDC researchers. Not only that: The number of people living with diagnosed DM in the US has remained stable for the past 8 years.

The findings represent the longest decline in new DM cases and the longest sustained plateau in existing cases. Between 1990 and 2009, the number of people living with diagnosed diabetes (DD) rose 4.4% per year, peaked at 8.2 per 100 adults, then leveled off at 8 per 100 in 2017. The trends were similar across age groups, racial and ethnic groups, and genders.

In part, the plateau may be due to the fact that people with DM are living longer, the researchers suggest, pointing to recent reports of a decline in cardiovascular and all-cause mortality in adults with DD.

But maybe the work to “stem the tide of type 2 diabetes” is finally having an effect, says Ann Albright, PhD, director of the CDC Division of Diabetes Translation. She stresses the importance of “putting science-proven programs into action,” citing the National Diabetes Prevention Program as a prime example. But she adds, “We must also increase access to affordable, healthier foods, and safe places to be active.”

The news about the decrease in new diabetes cases comes simultaneously with findings from the Restoring Insulin Secretion (RISE) Adult and Pediatric Medication Studies, which found that type 2 diabetes mellitus (T2DM) progression slows during treatment but resumes after treatment stops.

The research, funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was aimed at finding ways to preserve β-cell function. The adult study randomly assigned participants aged 20 to 65 years to receive long-acting insulin (glargine) for 3 months, followed by metformin for 9 months; liraglutide with metformin for 12 months; metformin alone for 12 months; or placebo. Participants’ β-cell function and blood glucose control improved on the treatments, with those in the liraglutide/metformin group showing the most improvement. But the improvements did not persist after treatment ended. “[T]reatment options were equally effective while people were actively on them,” says study chair Dr. Steven Kahn, from the VA Puget Sound Health Care System. “But people need to stay on treatment to maintain the benefits.”

The youth study (participants aged 10-19 years) study compared 3 months of insulin glargine, followed by metformin for 9 months, to metformin alone for 12 months. (Insulin glargine and metformin are the only FDA-approved drugs for young people with T2D )  β-cell function declined in the 2 pediatric treatment groups and even worsened after treatment ended. The studies support earlier evidence that T2DM affects young people differently and more aggressively than it does in adults, NIDDK Director Dr. Griffin Rodgers says.

Other research news is brighter for people at risk for type 1 diabetes mellitus (T1DM): An NIH-funded study found that treatment with teplizumab, an anti-CD3 monoclonal antibody, delayed clinical T1DM by ≥ 2 years.

Previous research had found that teplizumab slows the loss of β cells in people with recent-onset clinical T1DM, but the drug had not been tested in people without clinical disease. The researchers wanted to see whether early intervention would have a benefit for people at high risk. They compared a 14-day course of teplizumab with placebo in 76 participants aged 8 to 49 years who were relatives of people with T1DM, had at ≥ 2 types of DM-related autoantibodies, and had abnormal glucose tolerance.

During the trial, 72% of people on placebo developed clinical DM compared with 43% of those in the treatment group. The median time for the control participants to develop DM was just over 24 months vs 48 months in the teplizumab group. The effects of the drug were greatest in the first year after it was given, when 41% of the participants—mainly in the placebo group—developed clinical diabetes.

At-risk children and adolescents are known to progress to T1DM faster than adults, the researchers note. They say faster progression is associated with a highly active immune system, which may explain the impact of immune system-modulating drugs like teplizumab.

The study “illustrates how decades of research on the biology of T1D can lead to promising treatments that have a real impact on people’s lives,” NIDDK Director Rodgers says.

But the T1DM and T2DM studies, although highlighting areas of effectiveness, also underscore the continued need for new approaches to prevent and treat DM in young people.

Although the drop in new cases of T2DM are still unclear, the CDC researchers suggest that they are driven in part by increased awareness of DM prevention, changes in diet, changes in physical activity, and changes in diagnostic and screening practices. In other words, prevention also remains an urgent need.

After 20 years on the rise, new cases of diagnosed diabetes mellitus (DM) in the US have declined by 35%, from 1.7 million in 2008 to 1.3 million in 2017, according to CDC researchers. Not only that: The number of people living with diagnosed DM in the US has remained stable for the past 8 years.

The findings represent the longest decline in new DM cases and the longest sustained plateau in existing cases. Between 1990 and 2009, the number of people living with diagnosed diabetes (DD) rose 4.4% per year, peaked at 8.2 per 100 adults, then leveled off at 8 per 100 in 2017. The trends were similar across age groups, racial and ethnic groups, and genders.

In part, the plateau may be due to the fact that people with DM are living longer, the researchers suggest, pointing to recent reports of a decline in cardiovascular and all-cause mortality in adults with DD.

But maybe the work to “stem the tide of type 2 diabetes” is finally having an effect, says Ann Albright, PhD, director of the CDC Division of Diabetes Translation. She stresses the importance of “putting science-proven programs into action,” citing the National Diabetes Prevention Program as a prime example. But she adds, “We must also increase access to affordable, healthier foods, and safe places to be active.”

The news about the decrease in new diabetes cases comes simultaneously with findings from the Restoring Insulin Secretion (RISE) Adult and Pediatric Medication Studies, which found that type 2 diabetes mellitus (T2DM) progression slows during treatment but resumes after treatment stops.

The research, funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was aimed at finding ways to preserve β-cell function. The adult study randomly assigned participants aged 20 to 65 years to receive long-acting insulin (glargine) for 3 months, followed by metformin for 9 months; liraglutide with metformin for 12 months; metformin alone for 12 months; or placebo. Participants’ β-cell function and blood glucose control improved on the treatments, with those in the liraglutide/metformin group showing the most improvement. But the improvements did not persist after treatment ended. “[T]reatment options were equally effective while people were actively on them,” says study chair Dr. Steven Kahn, from the VA Puget Sound Health Care System. “But people need to stay on treatment to maintain the benefits.”

The youth study (participants aged 10-19 years) study compared 3 months of insulin glargine, followed by metformin for 9 months, to metformin alone for 12 months. (Insulin glargine and metformin are the only FDA-approved drugs for young people with T2D )  β-cell function declined in the 2 pediatric treatment groups and even worsened after treatment ended. The studies support earlier evidence that T2DM affects young people differently and more aggressively than it does in adults, NIDDK Director Dr. Griffin Rodgers says.

Other research news is brighter for people at risk for type 1 diabetes mellitus (T1DM): An NIH-funded study found that treatment with teplizumab, an anti-CD3 monoclonal antibody, delayed clinical T1DM by ≥ 2 years.

Previous research had found that teplizumab slows the loss of β cells in people with recent-onset clinical T1DM, but the drug had not been tested in people without clinical disease. The researchers wanted to see whether early intervention would have a benefit for people at high risk. They compared a 14-day course of teplizumab with placebo in 76 participants aged 8 to 49 years who were relatives of people with T1DM, had at ≥ 2 types of DM-related autoantibodies, and had abnormal glucose tolerance.

During the trial, 72% of people on placebo developed clinical DM compared with 43% of those in the treatment group. The median time for the control participants to develop DM was just over 24 months vs 48 months in the teplizumab group. The effects of the drug were greatest in the first year after it was given, when 41% of the participants—mainly in the placebo group—developed clinical diabetes.

At-risk children and adolescents are known to progress to T1DM faster than adults, the researchers note. They say faster progression is associated with a highly active immune system, which may explain the impact of immune system-modulating drugs like teplizumab.

The study “illustrates how decades of research on the biology of T1D can lead to promising treatments that have a real impact on people’s lives,” NIDDK Director Rodgers says.

But the T1DM and T2DM studies, although highlighting areas of effectiveness, also underscore the continued need for new approaches to prevent and treat DM in young people.

Although the drop in new cases of T2DM are still unclear, the CDC researchers suggest that they are driven in part by increased awareness of DM prevention, changes in diet, changes in physical activity, and changes in diagnostic and screening practices. In other words, prevention also remains an urgent need.

Atypical vascular lesions (AVLs) are rare flesh-colored, erythematous, or violaceous macules, patches, papules, or plaques that may occur following adjuvant radiation in breast cancer patients who have undergone conservative lumpectomy.^1,2 They range in size from 1 mm to 6 cm and are most often confined to the radiation field. Presentation occurs 1 to 20 years following radiation, though the lesions most often present within 5 years.^1,2 Although generally considered benign, 2 of 29 cases of AVLs progressed to angiosarcoma over a 5-year follow-up period in a retrospective clinicopathologic study.¹

Atypical vascular lesions show considerable histologic and clinical overlap with radiation-induced angiosarcomas (RIAs), making differentiation between the two challenging.^3,4 Mentzel et al⁵ compared benign, atypical, and malignant postradiation vascular lesions with nonradiation-associated angiosarcomas and found that RIAs were highly variable histopathologically, ranging from well differentiated to poorly differentiated, with atypia ranging from mild to severe. Radiation-induced angiosarcomas could be distinguished from AVLs and nonradiation-associated angiosarcomas by their oncogene amplification and protein expression profiles. Most strikingly, they found amplification of the MYC oncogene by fluorescence in situ hybridization in the nucleus of almost all the RIA cells, which was not seen in AVLs or nonradiation-associated angiosarcomas. Similarly, they found positive nuclear staining for MYC protein by immunohistochemistry in the nucleus of almost all cases of RIA but not in AVL or nonradiation-associated angiosarcomas, making MYC staining a useful diagnostic marker.⁵ In contrast, a study by Patton et al¹ concluded that AVLs demonstrate morphologic patterns and clinical outcomes that suggest they are precursors of angiosarcoma rather than just markers of risk.

Atypical vascular lesions and RIAs usually follow a total radiation dose of 40 to 50 Gy, but RIAs typically are diagnosed later (approximately 10 years following exposure).^6,7 Although RIAs are rare, they are known to be aggressive and often high grade, with a median survival of less than 5 years.^6,7 Survival is poor even with radical surgical treatment.⁸ We present a patient with at least 29 AVLs following breast-conserving surgery and radiation and suggest the need for increased awareness of the elevated risk for RIA in patients with numerous benign AVLs.

Case Report

A 43-year-old woman with a history of breast cancer who underwent breast-conserving lumpectomy and adjuvant radiation presented to dermatology upon referral from surgical oncology for multiple lesions on the right breast (Figure 1). Seven years prior to presentation she was diagnosed with grade 3 poorly differentiated invasive ductal carcinoma with lobular features in the right breast that was positive for human epidermal growth factor receptor 2 but negative for estrogen or progesterone receptors. She was given neoadjuvant treatment with trastuzumab, docetaxel, and carboplatin prior to conservation lumpectomy with adjuvant radiation. She received a total dose of 50.4 Gy in 28 fractions of 1.8 Gy each over 1 month, with a final boost of 10 Gy in 5 fractions of 2 Gy, each with local skin irritation as the only concern posttreatment.

She initially presented to dermatology approximately 3 years after radiotherapy (5 years prior to current presentation) with lesions on the breast that had been present for 6 to 9 months. Physical examination showed 2 firm, painless, 4- to 5-mm papules on the right upper breast. The patient was reassured that the lesions were not suspicious for malignancy; however, 3 years later she presented to surgical oncology with 8 bluish papules or macules (all approximately 4 mm in diameter) on the right breast. These lesions were biopsied and examined by 2 institutions. Pathology of the initial punch biopsy favored a diagnosis of AVLs, though the possibility of RIA could not be ruled out without a complete excisional biopsy. Two excisional biopsies a month later were again consistent with AVLs. In all cases, the lesions were negative for MYC protein. The patient was again reassured but referred to dermatology for a second opinion.

At the current presentation, physical examination showed at least 29 subcutaneous nodules on the right breast ranging in color from pink to deep blue to flesh colored with others more superficially hyperpigmented, possibly secondary to prior biopsy, and measuring 2 to 8 mm in diameter. Histopathologic examination of the biopsy specimens showed a vascular proliferation extending from the dermis into the subcutaneous tissue comprised of dilated and cavernous vascular channels lined by a single layer of endothelial cells with minimal cytologic atypia (Figure 2). There were focal areas of anastomosing slitlike vascular spaces dissecting dermal collagen. No features of malignancy, such as nuclear crowding, multilayering, or increased mitotic activity, were evident. Immunohistochemical studies for MYC protein were negative. The overall morphologic features and immunoprofile were felt to be most consistent with postradiation AVLs.

Comment

Conservative breast cancer surgery and radiotherapy are becoming more prevalent for breast cancer treatment, thus the number of patients likely to present with AVLs has increased. These patients are at risk for transformation to RIAs.⁶ It is important for clinicians to be aware of the diagnosis of both AVLs and RIAs and their management given their more frequent presentation. In most cases, one or a few AVLs are present, and excision is the treatment of choice. In a retrospective study by Brenn and Fletcher³ examining 16 patients with AVLs and 26 patients with RIA, the majority of cases of AVL had a single lesion and the maximum number of AVLs was 4. One patient in their study had 30 AVLs (each 3–4 mm in diameter), and she was diagnosed with RIA.³ Our patient—with at least 29 identifiable AVL lesions—was felt to be at considerable risk for developing RIA, as the only other case reported with this many AVLs developed RIA.¹ Given the large number of lesions, it was neither feasible to excise each one individually nor monitor all of them for malignant transformation.

Our case demonstrates the important role dermatologists may play in orchestrating care by a multispecialty team including oncology, radiation oncology, surgery, and plastic surgery. In our patient, a close examination of the literature by the dermatology team led to recognition of the potentially elevated risk for malignant transformation. The dermatology team also brought the case for review at the tumor board.

Although future studies are required to determine the relationship between AVL burden and the risk for progression to RIA, it is clear that a multidisciplinary approach and careful consideration of the current literature can prevent unnecessary morbidity and mortality for patients with this increasingly common problem.

Atypical vascular lesions (AVLs) are rare flesh-colored, erythematous, or violaceous macules, patches, papules, or plaques that may occur following adjuvant radiation in breast cancer patients who have undergone conservative lumpectomy.^1,2 They range in size from 1 mm to 6 cm and are most often confined to the radiation field. Presentation occurs 1 to 20 years following radiation, though the lesions most often present within 5 years.^1,2 Although generally considered benign, 2 of 29 cases of AVLs progressed to angiosarcoma over a 5-year follow-up period in a retrospective clinicopathologic study.¹

Atypical vascular lesions show considerable histologic and clinical overlap with radiation-induced angiosarcomas (RIAs), making differentiation between the two challenging.^3,4 Mentzel et al⁵ compared benign, atypical, and malignant postradiation vascular lesions with nonradiation-associated angiosarcomas and found that RIAs were highly variable histopathologically, ranging from well differentiated to poorly differentiated, with atypia ranging from mild to severe. Radiation-induced angiosarcomas could be distinguished from AVLs and nonradiation-associated angiosarcomas by their oncogene amplification and protein expression profiles. Most strikingly, they found amplification of the MYC oncogene by fluorescence in situ hybridization in the nucleus of almost all the RIA cells, which was not seen in AVLs or nonradiation-associated angiosarcomas. Similarly, they found positive nuclear staining for MYC protein by immunohistochemistry in the nucleus of almost all cases of RIA but not in AVL or nonradiation-associated angiosarcomas, making MYC staining a useful diagnostic marker.⁵ In contrast, a study by Patton et al¹ concluded that AVLs demonstrate morphologic patterns and clinical outcomes that suggest they are precursors of angiosarcoma rather than just markers of risk.

Atypical vascular lesions and RIAs usually follow a total radiation dose of 40 to 50 Gy, but RIAs typically are diagnosed later (approximately 10 years following exposure).^6,7 Although RIAs are rare, they are known to be aggressive and often high grade, with a median survival of less than 5 years.^6,7 Survival is poor even with radical surgical treatment.⁸ We present a patient with at least 29 AVLs following breast-conserving surgery and radiation and suggest the need for increased awareness of the elevated risk for RIA in patients with numerous benign AVLs.

Case Report

A 43-year-old woman with a history of breast cancer who underwent breast-conserving lumpectomy and adjuvant radiation presented to dermatology upon referral from surgical oncology for multiple lesions on the right breast (Figure 1). Seven years prior to presentation she was diagnosed with grade 3 poorly differentiated invasive ductal carcinoma with lobular features in the right breast that was positive for human epidermal growth factor receptor 2 but negative for estrogen or progesterone receptors. She was given neoadjuvant treatment with trastuzumab, docetaxel, and carboplatin prior to conservation lumpectomy with adjuvant radiation. She received a total dose of 50.4 Gy in 28 fractions of 1.8 Gy each over 1 month, with a final boost of 10 Gy in 5 fractions of 2 Gy, each with local skin irritation as the only concern posttreatment.

She initially presented to dermatology approximately 3 years after radiotherapy (5 years prior to current presentation) with lesions on the breast that had been present for 6 to 9 months. Physical examination showed 2 firm, painless, 4- to 5-mm papules on the right upper breast. The patient was reassured that the lesions were not suspicious for malignancy; however, 3 years later she presented to surgical oncology with 8 bluish papules or macules (all approximately 4 mm in diameter) on the right breast. These lesions were biopsied and examined by 2 institutions. Pathology of the initial punch biopsy favored a diagnosis of AVLs, though the possibility of RIA could not be ruled out without a complete excisional biopsy. Two excisional biopsies a month later were again consistent with AVLs. In all cases, the lesions were negative for MYC protein. The patient was again reassured but referred to dermatology for a second opinion.

At the current presentation, physical examination showed at least 29 subcutaneous nodules on the right breast ranging in color from pink to deep blue to flesh colored with others more superficially hyperpigmented, possibly secondary to prior biopsy, and measuring 2 to 8 mm in diameter. Histopathologic examination of the biopsy specimens showed a vascular proliferation extending from the dermis into the subcutaneous tissue comprised of dilated and cavernous vascular channels lined by a single layer of endothelial cells with minimal cytologic atypia (Figure 2). There were focal areas of anastomosing slitlike vascular spaces dissecting dermal collagen. No features of malignancy, such as nuclear crowding, multilayering, or increased mitotic activity, were evident. Immunohistochemical studies for MYC protein were negative. The overall morphologic features and immunoprofile were felt to be most consistent with postradiation AVLs.

Comment

Conservative breast cancer surgery and radiotherapy are becoming more prevalent for breast cancer treatment, thus the number of patients likely to present with AVLs has increased. These patients are at risk for transformation to RIAs.⁶ It is important for clinicians to be aware of the diagnosis of both AVLs and RIAs and their management given their more frequent presentation. In most cases, one or a few AVLs are present, and excision is the treatment of choice. In a retrospective study by Brenn and Fletcher³ examining 16 patients with AVLs and 26 patients with RIA, the majority of cases of AVL had a single lesion and the maximum number of AVLs was 4. One patient in their study had 30 AVLs (each 3–4 mm in diameter), and she was diagnosed with RIA.³ Our patient—with at least 29 identifiable AVL lesions—was felt to be at considerable risk for developing RIA, as the only other case reported with this many AVLs developed RIA.¹ Given the large number of lesions, it was neither feasible to excise each one individually nor monitor all of them for malignant transformation.

Our case demonstrates the important role dermatologists may play in orchestrating care by a multispecialty team including oncology, radiation oncology, surgery, and plastic surgery. In our patient, a close examination of the literature by the dermatology team led to recognition of the potentially elevated risk for malignant transformation. The dermatology team also brought the case for review at the tumor board.

Although future studies are required to determine the relationship between AVL burden and the risk for progression to RIA, it is clear that a multidisciplinary approach and careful consideration of the current literature can prevent unnecessary morbidity and mortality for patients with this increasingly common problem.

Atypical vascular lesions (AVLs) are rare flesh-colored, erythematous, or violaceous macules, patches, papules, or plaques that may occur following adjuvant radiation in breast cancer patients who have undergone conservative lumpectomy.^1,2 They range in size from 1 mm to 6 cm and are most often confined to the radiation field. Presentation occurs 1 to 20 years following radiation, though the lesions most often present within 5 years.^1,2 Although generally considered benign, 2 of 29 cases of AVLs progressed to angiosarcoma over a 5-year follow-up period in a retrospective clinicopathologic study.¹

Atypical vascular lesions show considerable histologic and clinical overlap with radiation-induced angiosarcomas (RIAs), making differentiation between the two challenging.^3,4 Mentzel et al⁵ compared benign, atypical, and malignant postradiation vascular lesions with nonradiation-associated angiosarcomas and found that RIAs were highly variable histopathologically, ranging from well differentiated to poorly differentiated, with atypia ranging from mild to severe. Radiation-induced angiosarcomas could be distinguished from AVLs and nonradiation-associated angiosarcomas by their oncogene amplification and protein expression profiles. Most strikingly, they found amplification of the MYC oncogene by fluorescence in situ hybridization in the nucleus of almost all the RIA cells, which was not seen in AVLs or nonradiation-associated angiosarcomas. Similarly, they found positive nuclear staining for MYC protein by immunohistochemistry in the nucleus of almost all cases of RIA but not in AVL or nonradiation-associated angiosarcomas, making MYC staining a useful diagnostic marker.⁵ In contrast, a study by Patton et al¹ concluded that AVLs demonstrate morphologic patterns and clinical outcomes that suggest they are precursors of angiosarcoma rather than just markers of risk.

Atypical vascular lesions and RIAs usually follow a total radiation dose of 40 to 50 Gy, but RIAs typically are diagnosed later (approximately 10 years following exposure).^6,7 Although RIAs are rare, they are known to be aggressive and often high grade, with a median survival of less than 5 years.^6,7 Survival is poor even with radical surgical treatment.⁸ We present a patient with at least 29 AVLs following breast-conserving surgery and radiation and suggest the need for increased awareness of the elevated risk for RIA in patients with numerous benign AVLs.

Case Report

A 43-year-old woman with a history of breast cancer who underwent breast-conserving lumpectomy and adjuvant radiation presented to dermatology upon referral from surgical oncology for multiple lesions on the right breast (Figure 1). Seven years prior to presentation she was diagnosed with grade 3 poorly differentiated invasive ductal carcinoma with lobular features in the right breast that was positive for human epidermal growth factor receptor 2 but negative for estrogen or progesterone receptors. She was given neoadjuvant treatment with trastuzumab, docetaxel, and carboplatin prior to conservation lumpectomy with adjuvant radiation. She received a total dose of 50.4 Gy in 28 fractions of 1.8 Gy each over 1 month, with a final boost of 10 Gy in 5 fractions of 2 Gy, each with local skin irritation as the only concern posttreatment.

She initially presented to dermatology approximately 3 years after radiotherapy (5 years prior to current presentation) with lesions on the breast that had been present for 6 to 9 months. Physical examination showed 2 firm, painless, 4- to 5-mm papules on the right upper breast. The patient was reassured that the lesions were not suspicious for malignancy; however, 3 years later she presented to surgical oncology with 8 bluish papules or macules (all approximately 4 mm in diameter) on the right breast. These lesions were biopsied and examined by 2 institutions. Pathology of the initial punch biopsy favored a diagnosis of AVLs, though the possibility of RIA could not be ruled out without a complete excisional biopsy. Two excisional biopsies a month later were again consistent with AVLs. In all cases, the lesions were negative for MYC protein. The patient was again reassured but referred to dermatology for a second opinion.

At the current presentation, physical examination showed at least 29 subcutaneous nodules on the right breast ranging in color from pink to deep blue to flesh colored with others more superficially hyperpigmented, possibly secondary to prior biopsy, and measuring 2 to 8 mm in diameter. Histopathologic examination of the biopsy specimens showed a vascular proliferation extending from the dermis into the subcutaneous tissue comprised of dilated and cavernous vascular channels lined by a single layer of endothelial cells with minimal cytologic atypia (Figure 2). There were focal areas of anastomosing slitlike vascular spaces dissecting dermal collagen. No features of malignancy, such as nuclear crowding, multilayering, or increased mitotic activity, were evident. Immunohistochemical studies for MYC protein were negative. The overall morphologic features and immunoprofile were felt to be most consistent with postradiation AVLs.

Comment

Conservative breast cancer surgery and radiotherapy are becoming more prevalent for breast cancer treatment, thus the number of patients likely to present with AVLs has increased. These patients are at risk for transformation to RIAs.⁶ It is important for clinicians to be aware of the diagnosis of both AVLs and RIAs and their management given their more frequent presentation. In most cases, one or a few AVLs are present, and excision is the treatment of choice. In a retrospective study by Brenn and Fletcher³ examining 16 patients with AVLs and 26 patients with RIA, the majority of cases of AVL had a single lesion and the maximum number of AVLs was 4. One patient in their study had 30 AVLs (each 3–4 mm in diameter), and she was diagnosed with RIA.³ Our patient—with at least 29 identifiable AVL lesions—was felt to be at considerable risk for developing RIA, as the only other case reported with this many AVLs developed RIA.¹ Given the large number of lesions, it was neither feasible to excise each one individually nor monitor all of them for malignant transformation.

Our case demonstrates the important role dermatologists may play in orchestrating care by a multispecialty team including oncology, radiation oncology, surgery, and plastic surgery. In our patient, a close examination of the literature by the dermatology team led to recognition of the potentially elevated risk for malignant transformation. The dermatology team also brought the case for review at the tumor board.

Although future studies are required to determine the relationship between AVL burden and the risk for progression to RIA, it is clear that a multidisciplinary approach and careful consideration of the current literature can prevent unnecessary morbidity and mortality for patients with this increasingly common problem.

“So you want to be a gastroenterologist? What do you really want to do?” This is not an uncommon question that a trainee is faced with when progressing through residency and gastroenterology fellowship.

The list of possibilities includes general gastroenterology, advanced endoscopy, transplant hepatology, and neurogastroenterology and motility. From there, each subspecialty can be broken down further into organ system or a specific procedure of interest. Another necessary question is whether to pursue a career in academics or private practice. When it comes to the decision to proceed with a fellowship in neurogastroenterology and motility, there are two pathways that can be taken. The first is for the resident who is interested in gaining experience in gastroenterology prior to starting a general gastroenterology fellowship (there are two programs that currently allow for this pathway). The other track is for those who have completed a general gastroenterology fellowship and are looking to enhance their academic careers by pursuing additional training in neurogastroenterology and motility.

There is currently a need for gastroenterologists interested in neurogastroenterology and motility. Among the most common diagnoses in an ambulatory setting, based on International Classification of Disease (ICD) coding, are abdominal pain, gastroesophageal reflux disease, constipation, nausea and vomiting, irritable bowel syndrome, functional dyspepsia, and dysphagia.^1,2 While many fellows are exposed to a wide range of motility patients during general gastroenterology fellowship, there is typically not a sufficient amount of training to attain “level 2” proficiency.^2,3 In an effort to help standardize training there are recommended thresholds established and advanced training in neurogastroenterology and motility can help fellows to attain that proficiency.^2,3 The extra year can also help you prepare to run a motility lab, train nurses, establish lab protocols and quality standards, and manage referrals, which are important skills as a neurogastroenterology and motility specialist.
 

Types of programs

There are several different types of motility programs available. As mentioned previously, some programs afford individuals an opportunity to gain additional experience in gastroenterology before progressing to general gastroenterology fellowship. There are two programs that offer a 1-year fellowship in neurogastroenterology and motility, both prior to or after a general gastroenterology fellowship. Four programs offer 1-year neurogastroenterology and motility fellowships only after a general gastroenterology fellowship. While the neurogastroenterology and motility fellowships cover esophageal motility, there are four programs that specifically focus solely on the esophagus (Table 1).

Where to find programs

Currently, there is not a singular list of neurogastroenterology and motility programs available for review as you might find with an Accreditation Council for Graduate Medical Education (ACGME) residency or fellowship. At present, the best way to identify the available programs is to search online. Motivation to select a specific program may be related to individual preference and can include geography and department expertise; this ultimately helps to create a focused list. With regard to the ANMS 1-month Clinical Training Program, the list of available programs is available on the society’s website and is for fellows currently in training who wish to incorporate neurogastroenterology and motility into their general GI fellowship.

How to apply

Advanced training in neurogastroenterology and motility is currently a non-ACGME pathway and does not offer a match process for its applicants. After identifying a program of interest, one can find specific instructions on how to apply at the programs’ websites. Typically the process involves reaching out to the program director, writing a letter of interest or personal statement, providing letters of recommendation, and interviewing. Each program has some variability in what is required and attention should be paid to the criteria listed on the specific website.

My experience

I was fortunate to have substantial exposure to esophageal motility in my general gastroenterology fellowship. Gaining this experience was invaluable and laid the foundation for my interest in neurogastroenterology and motility, and, specifically, esophageal dysmotility. My interest in neurogastroenterology and motility then collided with my desire to pursue a career in academics. Knowing the general trajectory for my future career, I began exploring the possibility of undergoing an additional 1-year fellowship early in my second year of GI fellowship. I worked closely with my program director to help define my future goals and to identify available places that would help me attain those goals. While I continued to have an interest in the esophagus, additional training in neurogastroenterology and motility would broaden my understanding and enhance my ability to manage complex patients and perform research at a tertiary care center. I investigated the different neurogastroenterology and motility fellowship programs online and followed the online application instructions. Utilizing national gastroenterology society conferences as networking opportunities, I was able to meet with the program director of my current neurogastroenterology and motility fellowship. In my third year of general gastroenterology fellowship I formally interviewed with the motility group at Johns Hopkins and was later accepted into the neurogastroenterology and motility fellowship program.

Now, nearing the end of my 1-year neurogastroenterology and motility fellowship, I reflect on my extremely positive experience. Throughout the course of the year I have been able to work with multiple GI providers — each with their own area of expertise within the field. There has been a profound exposure to a wide variety of patients with a spectrum of motility conditions covering the entire GI tract. There has been ample opportunity to read motility studies with the guidance and support of the motility faculty to further enhance my skills. The additional year has broadened my exposure to, and the management of, the biopsychosocial aspect of this specific patient population. In line with that, I have had the ability to grow with regard to my use of pharmacology and recognize which symptom might benefit from a particular neuromodulator. An emphasis was also placed on learning the gut-brain axis, and, through multidisciplinary clinics, I worked closely with other disciplines such as psychiatry and GI clinical psychology. Furthermore, the additional year has allowed me to be involved in several research projects within neurogastroenterology and motility that will undoubtedly enhance my future career.

 

Conclusion

Deciding to pursue an additional year in neurogastroenterology and motility has been one that has helped to give a solid direction to my budding career. It has left me confident in managing this diverse and complex patient population and has helped prepare me for a career in academic gastroenterology. For those who are interested in academic neurogastroenterology and motility, an additional fellowship can help define you as a gastroenterologist and help you to pursue the career of your dreams.

Dr. Sloan is a clinical instructor in the division of gastroenterology at Johns Hopkins in Baltimore.

References

1. Peery A. et al. Burden of gastrointestinal, liver, and pancreatic disease in the United States. Gastroenterology 2015;149:1731-41.e3.

2. Rao S., Parkman H. Advanced training in neurogastroenterology and gastrointestinal motility. Gastroenterology 2015;148:881-5.

3. American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association (AGA) Institute, and American Society for Gastrointestinal Endoscopy. The gastroenterology core curriculum, third edition. Gastroenterology 2007;132:2012-18.

“So you want to be a gastroenterologist? What do you really want to do?” This is not an uncommon question that a trainee is faced with when progressing through residency and gastroenterology fellowship.

The list of possibilities includes general gastroenterology, advanced endoscopy, transplant hepatology, and neurogastroenterology and motility. From there, each subspecialty can be broken down further into organ system or a specific procedure of interest. Another necessary question is whether to pursue a career in academics or private practice. When it comes to the decision to proceed with a fellowship in neurogastroenterology and motility, there are two pathways that can be taken. The first is for the resident who is interested in gaining experience in gastroenterology prior to starting a general gastroenterology fellowship (there are two programs that currently allow for this pathway). The other track is for those who have completed a general gastroenterology fellowship and are looking to enhance their academic careers by pursuing additional training in neurogastroenterology and motility.

There is currently a need for gastroenterologists interested in neurogastroenterology and motility. Among the most common diagnoses in an ambulatory setting, based on International Classification of Disease (ICD) coding, are abdominal pain, gastroesophageal reflux disease, constipation, nausea and vomiting, irritable bowel syndrome, functional dyspepsia, and dysphagia.^1,2 While many fellows are exposed to a wide range of motility patients during general gastroenterology fellowship, there is typically not a sufficient amount of training to attain “level 2” proficiency.^2,3 In an effort to help standardize training there are recommended thresholds established and advanced training in neurogastroenterology and motility can help fellows to attain that proficiency.^2,3 The extra year can also help you prepare to run a motility lab, train nurses, establish lab protocols and quality standards, and manage referrals, which are important skills as a neurogastroenterology and motility specialist.
 

Types of programs

There are several different types of motility programs available. As mentioned previously, some programs afford individuals an opportunity to gain additional experience in gastroenterology before progressing to general gastroenterology fellowship. There are two programs that offer a 1-year fellowship in neurogastroenterology and motility, both prior to or after a general gastroenterology fellowship. Four programs offer 1-year neurogastroenterology and motility fellowships only after a general gastroenterology fellowship. While the neurogastroenterology and motility fellowships cover esophageal motility, there are four programs that specifically focus solely on the esophagus (Table 1).

Where to find programs

Currently, there is not a singular list of neurogastroenterology and motility programs available for review as you might find with an Accreditation Council for Graduate Medical Education (ACGME) residency or fellowship. At present, the best way to identify the available programs is to search online. Motivation to select a specific program may be related to individual preference and can include geography and department expertise; this ultimately helps to create a focused list. With regard to the ANMS 1-month Clinical Training Program, the list of available programs is available on the society’s website and is for fellows currently in training who wish to incorporate neurogastroenterology and motility into their general GI fellowship.

How to apply

Advanced training in neurogastroenterology and motility is currently a non-ACGME pathway and does not offer a match process for its applicants. After identifying a program of interest, one can find specific instructions on how to apply at the programs’ websites. Typically the process involves reaching out to the program director, writing a letter of interest or personal statement, providing letters of recommendation, and interviewing. Each program has some variability in what is required and attention should be paid to the criteria listed on the specific website.

My experience

I was fortunate to have substantial exposure to esophageal motility in my general gastroenterology fellowship. Gaining this experience was invaluable and laid the foundation for my interest in neurogastroenterology and motility, and, specifically, esophageal dysmotility. My interest in neurogastroenterology and motility then collided with my desire to pursue a career in academics. Knowing the general trajectory for my future career, I began exploring the possibility of undergoing an additional 1-year fellowship early in my second year of GI fellowship. I worked closely with my program director to help define my future goals and to identify available places that would help me attain those goals. While I continued to have an interest in the esophagus, additional training in neurogastroenterology and motility would broaden my understanding and enhance my ability to manage complex patients and perform research at a tertiary care center. I investigated the different neurogastroenterology and motility fellowship programs online and followed the online application instructions. Utilizing national gastroenterology society conferences as networking opportunities, I was able to meet with the program director of my current neurogastroenterology and motility fellowship. In my third year of general gastroenterology fellowship I formally interviewed with the motility group at Johns Hopkins and was later accepted into the neurogastroenterology and motility fellowship program.

Now, nearing the end of my 1-year neurogastroenterology and motility fellowship, I reflect on my extremely positive experience. Throughout the course of the year I have been able to work with multiple GI providers — each with their own area of expertise within the field. There has been a profound exposure to a wide variety of patients with a spectrum of motility conditions covering the entire GI tract. There has been ample opportunity to read motility studies with the guidance and support of the motility faculty to further enhance my skills. The additional year has broadened my exposure to, and the management of, the biopsychosocial aspect of this specific patient population. In line with that, I have had the ability to grow with regard to my use of pharmacology and recognize which symptom might benefit from a particular neuromodulator. An emphasis was also placed on learning the gut-brain axis, and, through multidisciplinary clinics, I worked closely with other disciplines such as psychiatry and GI clinical psychology. Furthermore, the additional year has allowed me to be involved in several research projects within neurogastroenterology and motility that will undoubtedly enhance my future career.

 

Conclusion

Deciding to pursue an additional year in neurogastroenterology and motility has been one that has helped to give a solid direction to my budding career. It has left me confident in managing this diverse and complex patient population and has helped prepare me for a career in academic gastroenterology. For those who are interested in academic neurogastroenterology and motility, an additional fellowship can help define you as a gastroenterologist and help you to pursue the career of your dreams.

Dr. Sloan is a clinical instructor in the division of gastroenterology at Johns Hopkins in Baltimore.

References

1. Peery A. et al. Burden of gastrointestinal, liver, and pancreatic disease in the United States. Gastroenterology 2015;149:1731-41.e3.

2. Rao S., Parkman H. Advanced training in neurogastroenterology and gastrointestinal motility. Gastroenterology 2015;148:881-5.

3. American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association (AGA) Institute, and American Society for Gastrointestinal Endoscopy. The gastroenterology core curriculum, third edition. Gastroenterology 2007;132:2012-18.

“So you want to be a gastroenterologist? What do you really want to do?” This is not an uncommon question that a trainee is faced with when progressing through residency and gastroenterology fellowship.

The list of possibilities includes general gastroenterology, advanced endoscopy, transplant hepatology, and neurogastroenterology and motility. From there, each subspecialty can be broken down further into organ system or a specific procedure of interest. Another necessary question is whether to pursue a career in academics or private practice. When it comes to the decision to proceed with a fellowship in neurogastroenterology and motility, there are two pathways that can be taken. The first is for the resident who is interested in gaining experience in gastroenterology prior to starting a general gastroenterology fellowship (there are two programs that currently allow for this pathway). The other track is for those who have completed a general gastroenterology fellowship and are looking to enhance their academic careers by pursuing additional training in neurogastroenterology and motility.

There is currently a need for gastroenterologists interested in neurogastroenterology and motility. Among the most common diagnoses in an ambulatory setting, based on International Classification of Disease (ICD) coding, are abdominal pain, gastroesophageal reflux disease, constipation, nausea and vomiting, irritable bowel syndrome, functional dyspepsia, and dysphagia.^1,2 While many fellows are exposed to a wide range of motility patients during general gastroenterology fellowship, there is typically not a sufficient amount of training to attain “level 2” proficiency.^2,3 In an effort to help standardize training there are recommended thresholds established and advanced training in neurogastroenterology and motility can help fellows to attain that proficiency.^2,3 The extra year can also help you prepare to run a motility lab, train nurses, establish lab protocols and quality standards, and manage referrals, which are important skills as a neurogastroenterology and motility specialist.
 

Types of programs

There are several different types of motility programs available. As mentioned previously, some programs afford individuals an opportunity to gain additional experience in gastroenterology before progressing to general gastroenterology fellowship. There are two programs that offer a 1-year fellowship in neurogastroenterology and motility, both prior to or after a general gastroenterology fellowship. Four programs offer 1-year neurogastroenterology and motility fellowships only after a general gastroenterology fellowship. While the neurogastroenterology and motility fellowships cover esophageal motility, there are four programs that specifically focus solely on the esophagus (Table 1).

Where to find programs

Currently, there is not a singular list of neurogastroenterology and motility programs available for review as you might find with an Accreditation Council for Graduate Medical Education (ACGME) residency or fellowship. At present, the best way to identify the available programs is to search online. Motivation to select a specific program may be related to individual preference and can include geography and department expertise; this ultimately helps to create a focused list. With regard to the ANMS 1-month Clinical Training Program, the list of available programs is available on the society’s website and is for fellows currently in training who wish to incorporate neurogastroenterology and motility into their general GI fellowship.

How to apply

Advanced training in neurogastroenterology and motility is currently a non-ACGME pathway and does not offer a match process for its applicants. After identifying a program of interest, one can find specific instructions on how to apply at the programs’ websites. Typically the process involves reaching out to the program director, writing a letter of interest or personal statement, providing letters of recommendation, and interviewing. Each program has some variability in what is required and attention should be paid to the criteria listed on the specific website.

My experience

I was fortunate to have substantial exposure to esophageal motility in my general gastroenterology fellowship. Gaining this experience was invaluable and laid the foundation for my interest in neurogastroenterology and motility, and, specifically, esophageal dysmotility. My interest in neurogastroenterology and motility then collided with my desire to pursue a career in academics. Knowing the general trajectory for my future career, I began exploring the possibility of undergoing an additional 1-year fellowship early in my second year of GI fellowship. I worked closely with my program director to help define my future goals and to identify available places that would help me attain those goals. While I continued to have an interest in the esophagus, additional training in neurogastroenterology and motility would broaden my understanding and enhance my ability to manage complex patients and perform research at a tertiary care center. I investigated the different neurogastroenterology and motility fellowship programs online and followed the online application instructions. Utilizing national gastroenterology society conferences as networking opportunities, I was able to meet with the program director of my current neurogastroenterology and motility fellowship. In my third year of general gastroenterology fellowship I formally interviewed with the motility group at Johns Hopkins and was later accepted into the neurogastroenterology and motility fellowship program.

Now, nearing the end of my 1-year neurogastroenterology and motility fellowship, I reflect on my extremely positive experience. Throughout the course of the year I have been able to work with multiple GI providers — each with their own area of expertise within the field. There has been a profound exposure to a wide variety of patients with a spectrum of motility conditions covering the entire GI tract. There has been ample opportunity to read motility studies with the guidance and support of the motility faculty to further enhance my skills. The additional year has broadened my exposure to, and the management of, the biopsychosocial aspect of this specific patient population. In line with that, I have had the ability to grow with regard to my use of pharmacology and recognize which symptom might benefit from a particular neuromodulator. An emphasis was also placed on learning the gut-brain axis, and, through multidisciplinary clinics, I worked closely with other disciplines such as psychiatry and GI clinical psychology. Furthermore, the additional year has allowed me to be involved in several research projects within neurogastroenterology and motility that will undoubtedly enhance my future career.

 

Conclusion

Deciding to pursue an additional year in neurogastroenterology and motility has been one that has helped to give a solid direction to my budding career. It has left me confident in managing this diverse and complex patient population and has helped prepare me for a career in academic gastroenterology. For those who are interested in academic neurogastroenterology and motility, an additional fellowship can help define you as a gastroenterologist and help you to pursue the career of your dreams.

Dr. Sloan is a clinical instructor in the division of gastroenterology at Johns Hopkins in Baltimore.

References

1. Peery A. et al. Burden of gastrointestinal, liver, and pancreatic disease in the United States. Gastroenterology 2015;149:1731-41.e3.

2. Rao S., Parkman H. Advanced training in neurogastroenterology and gastrointestinal motility. Gastroenterology 2015;148:881-5.

3. American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association (AGA) Institute, and American Society for Gastrointestinal Endoscopy. The gastroenterology core curriculum, third edition. Gastroenterology 2007;132:2012-18.

As a first-year gastroenterology fellow, banding my first patient with a variceal bleed was an exciting – but also stress-provoking – event. What if I banded incorrectly and caused more bleeding? With a successful band, a patient’s hemorrhagic shock is now controlled, hemodynamics improved, and euphoria takes over. Now, in my third year of a gastroenterology fellowship but my first year of the American Gastroenterological Association (AGA) Editorial Fellowship, preparing to present the first manuscript that I handled to the Board of Editors at our weekly meeting has now induced the same excitement and need for the same level of dedication. Have I researched the foundational literature that this current manuscript was built on? What is the trajectory of this research and will this project be interesting to our readers and lead to breakthroughs in the field?

Gastroenterology is the premier flagship journal of the AGA and, in this Editorial Fellowship, I was selected to spend a fully immersive 1-year experience working on all aspects of this journal. In its second year of inception, I echo Dr. Eric Shah’s insight into the transformative and immersive nature of this fellowship.¹ In this role, I have made three developments, and each one has left me with a valuable lesson.

Mentorship

My first development was as a direct mentee under the leadership of the two editors in chief Richard Peek, MD, and Douglas Corley, MD, and associate editor John Inadomi, MD. In this role, I reviewed submitted manuscripts regarding outcome data of oncologic studies in the fields of colon, esophageal, and gastric cancer. I served as a reviewer for submitted manuscripts and discussed the impact, novelty, and decision for publication with the Board of Editors. In our weekly meetings, the associate editors discussed manuscripts that needed further review prior to acceptance, revision, or rejection. A few themes underpinned the discussion of these manuscripts:

• Is this science reproducible and is there scientific rigor for study design, validity, and analysis?
• How does this manuscript add to the current state of the literature?
• What is the trajectory of this research field?
• How will this manuscript lead to breakthroughs in this field?
• Are the advancements in this manuscript likely to lead to paradigm shifts in the field in its approach, design, or findings?

I also was fortunate to meet leaders in the field, including working daily in person with multiple members of the Board of Editors at Vanderbilt University Medical Center, Nashville, Tenn., as well as visiting professors, including Dr. Corley, Linda Rabeneck, MD, and T. Jake Liang, MD, who not only spoke on their scientific inquiries but also about their transitional path from gastroenterology fellows to pioneers in their respective fields. From these lessons, I have learned the scientific rigor of manuscript review for Gastroenterology and how to approach modern challenges in our field to directly improve patient care.
 

AGA’s commitment to early-career investigators

The Editorial Fellowship allowed me to expand a traditional third-year gastroenterology fellowship to dive deep into the intense path to get a manuscript published in Gastroenterology. Whereas 1 year prior, I had found dilating a complete esophageal stricture difficult, I now found myself learning to master clinical trial design, applying modern techniques of artificial intelligence, understanding organoid development, and navigating the impact of the microbiome. I was fortunate to be selected for Vanderbilt’s Master’s in Science in Clinical Investigation, which allowed me to apply my education not only to my own research but also to synergistically understand and deconstruct new submissions ranging from modern statistics with Bayesian modeling to analysis of large genetic data. All of this was built in the supportive framework of my mentoring committee.

As a fellow, I am inspired to see the multicenter, international collaboration to answer important questions in our field. Leveraging large databases and the expertise of multiple investigators, breakthroughs were made because of the collaborative nature of the science. This also was felt in the review process, where experts generously reviewed manuscripts to enhance the quality of the submission in order to advance knowledge in the field. Reading hundreds of these reviews this year has allowed me to refocus my current research studies and improve the way I write my current reviews. In the spirit of reproducible science and challenging the precision of study design, I was impressed by the time, effort, and dedication reviewers from our field spent to help improve the literature. Dr. Peek and Dr. Corley, our editors in chief, committed their time in discussing my innovations and critiques and displayed their level of interest in the opinions of early-career investigators and fostering the next generation of scientists and practitioners. In this lesson, I was invigorated by the depth of AGA opportunities for fellows and junior faculty in education, research, and involvement.
 

Self-reflection

Having the honor and privilege to review manuscripts upon submission also increased my critical view of my current practices. I now question the level of evidence for which current patient care practices are based, which allows me to better understand the research areas that need increased attention to improve the quality of our guidelines and evidence. For motivated fellows interested in a path of academic medicine, I would strongly advise applying for this prestigious fellowship. In no other training process could I have learned such a breadth of scientific skills and directly apply them to my patient care, my research, and my role as an educator. Furthermore, I was able to contribute to the reviewing and editing process, which allowed me to directly contribute to the field at an early stage of my career. In this final lesson, I exit this impactful Editorial Fellowship in self-reflection. I leave this fellowship humbled – by you – the reader who continues to learn to improve your patient care, the scientist as she works tirelessly to answer questions and contribute to the literature, the gastroenterology community for their willingness to teach and mentor fellows and early-career investigators and practitioners, and the patients who remind us that we all have a shared mission to advance scientific knowledge to improve patient care.

Dr. Naik is a gastroenterology fellow in the department of gastroenterology and hepatology at Vanderbilt University Medical Center in Nashville, Tenn.

Reference

1. Shah ED. Skills acquired during my 1-year AGA Editorial Fellowship. Gastroenterology. 2018;154(6):1563.

As a first-year gastroenterology fellow, banding my first patient with a variceal bleed was an exciting – but also stress-provoking – event. What if I banded incorrectly and caused more bleeding? With a successful band, a patient’s hemorrhagic shock is now controlled, hemodynamics improved, and euphoria takes over. Now, in my third year of a gastroenterology fellowship but my first year of the American Gastroenterological Association (AGA) Editorial Fellowship, preparing to present the first manuscript that I handled to the Board of Editors at our weekly meeting has now induced the same excitement and need for the same level of dedication. Have I researched the foundational literature that this current manuscript was built on? What is the trajectory of this research and will this project be interesting to our readers and lead to breakthroughs in the field?

Gastroenterology is the premier flagship journal of the AGA and, in this Editorial Fellowship, I was selected to spend a fully immersive 1-year experience working on all aspects of this journal. In its second year of inception, I echo Dr. Eric Shah’s insight into the transformative and immersive nature of this fellowship.¹ In this role, I have made three developments, and each one has left me with a valuable lesson.

Mentorship

My first development was as a direct mentee under the leadership of the two editors in chief Richard Peek, MD, and Douglas Corley, MD, and associate editor John Inadomi, MD. In this role, I reviewed submitted manuscripts regarding outcome data of oncologic studies in the fields of colon, esophageal, and gastric cancer. I served as a reviewer for submitted manuscripts and discussed the impact, novelty, and decision for publication with the Board of Editors. In our weekly meetings, the associate editors discussed manuscripts that needed further review prior to acceptance, revision, or rejection. A few themes underpinned the discussion of these manuscripts:

• Is this science reproducible and is there scientific rigor for study design, validity, and analysis?
• How does this manuscript add to the current state of the literature?
• What is the trajectory of this research field?
• How will this manuscript lead to breakthroughs in this field?
• Are the advancements in this manuscript likely to lead to paradigm shifts in the field in its approach, design, or findings?

I also was fortunate to meet leaders in the field, including working daily in person with multiple members of the Board of Editors at Vanderbilt University Medical Center, Nashville, Tenn., as well as visiting professors, including Dr. Corley, Linda Rabeneck, MD, and T. Jake Liang, MD, who not only spoke on their scientific inquiries but also about their transitional path from gastroenterology fellows to pioneers in their respective fields. From these lessons, I have learned the scientific rigor of manuscript review for Gastroenterology and how to approach modern challenges in our field to directly improve patient care.
 

AGA’s commitment to early-career investigators

The Editorial Fellowship allowed me to expand a traditional third-year gastroenterology fellowship to dive deep into the intense path to get a manuscript published in Gastroenterology. Whereas 1 year prior, I had found dilating a complete esophageal stricture difficult, I now found myself learning to master clinical trial design, applying modern techniques of artificial intelligence, understanding organoid development, and navigating the impact of the microbiome. I was fortunate to be selected for Vanderbilt’s Master’s in Science in Clinical Investigation, which allowed me to apply my education not only to my own research but also to synergistically understand and deconstruct new submissions ranging from modern statistics with Bayesian modeling to analysis of large genetic data. All of this was built in the supportive framework of my mentoring committee.

As a fellow, I am inspired to see the multicenter, international collaboration to answer important questions in our field. Leveraging large databases and the expertise of multiple investigators, breakthroughs were made because of the collaborative nature of the science. This also was felt in the review process, where experts generously reviewed manuscripts to enhance the quality of the submission in order to advance knowledge in the field. Reading hundreds of these reviews this year has allowed me to refocus my current research studies and improve the way I write my current reviews. In the spirit of reproducible science and challenging the precision of study design, I was impressed by the time, effort, and dedication reviewers from our field spent to help improve the literature. Dr. Peek and Dr. Corley, our editors in chief, committed their time in discussing my innovations and critiques and displayed their level of interest in the opinions of early-career investigators and fostering the next generation of scientists and practitioners. In this lesson, I was invigorated by the depth of AGA opportunities for fellows and junior faculty in education, research, and involvement.
 

Self-reflection

Having the honor and privilege to review manuscripts upon submission also increased my critical view of my current practices. I now question the level of evidence for which current patient care practices are based, which allows me to better understand the research areas that need increased attention to improve the quality of our guidelines and evidence. For motivated fellows interested in a path of academic medicine, I would strongly advise applying for this prestigious fellowship. In no other training process could I have learned such a breadth of scientific skills and directly apply them to my patient care, my research, and my role as an educator. Furthermore, I was able to contribute to the reviewing and editing process, which allowed me to directly contribute to the field at an early stage of my career. In this final lesson, I exit this impactful Editorial Fellowship in self-reflection. I leave this fellowship humbled – by you – the reader who continues to learn to improve your patient care, the scientist as she works tirelessly to answer questions and contribute to the literature, the gastroenterology community for their willingness to teach and mentor fellows and early-career investigators and practitioners, and the patients who remind us that we all have a shared mission to advance scientific knowledge to improve patient care.

Dr. Naik is a gastroenterology fellow in the department of gastroenterology and hepatology at Vanderbilt University Medical Center in Nashville, Tenn.

Reference

1. Shah ED. Skills acquired during my 1-year AGA Editorial Fellowship. Gastroenterology. 2018;154(6):1563.

As a first-year gastroenterology fellow, banding my first patient with a variceal bleed was an exciting – but also stress-provoking – event. What if I banded incorrectly and caused more bleeding? With a successful band, a patient’s hemorrhagic shock is now controlled, hemodynamics improved, and euphoria takes over. Now, in my third year of a gastroenterology fellowship but my first year of the American Gastroenterological Association (AGA) Editorial Fellowship, preparing to present the first manuscript that I handled to the Board of Editors at our weekly meeting has now induced the same excitement and need for the same level of dedication. Have I researched the foundational literature that this current manuscript was built on? What is the trajectory of this research and will this project be interesting to our readers and lead to breakthroughs in the field?

Gastroenterology is the premier flagship journal of the AGA and, in this Editorial Fellowship, I was selected to spend a fully immersive 1-year experience working on all aspects of this journal. In its second year of inception, I echo Dr. Eric Shah’s insight into the transformative and immersive nature of this fellowship.¹ In this role, I have made three developments, and each one has left me with a valuable lesson.

Mentorship

My first development was as a direct mentee under the leadership of the two editors in chief Richard Peek, MD, and Douglas Corley, MD, and associate editor John Inadomi, MD. In this role, I reviewed submitted manuscripts regarding outcome data of oncologic studies in the fields of colon, esophageal, and gastric cancer. I served as a reviewer for submitted manuscripts and discussed the impact, novelty, and decision for publication with the Board of Editors. In our weekly meetings, the associate editors discussed manuscripts that needed further review prior to acceptance, revision, or rejection. A few themes underpinned the discussion of these manuscripts:

• Is this science reproducible and is there scientific rigor for study design, validity, and analysis?
• How does this manuscript add to the current state of the literature?
• What is the trajectory of this research field?
• How will this manuscript lead to breakthroughs in this field?
• Are the advancements in this manuscript likely to lead to paradigm shifts in the field in its approach, design, or findings?

I also was fortunate to meet leaders in the field, including working daily in person with multiple members of the Board of Editors at Vanderbilt University Medical Center, Nashville, Tenn., as well as visiting professors, including Dr. Corley, Linda Rabeneck, MD, and T. Jake Liang, MD, who not only spoke on their scientific inquiries but also about their transitional path from gastroenterology fellows to pioneers in their respective fields. From these lessons, I have learned the scientific rigor of manuscript review for Gastroenterology and how to approach modern challenges in our field to directly improve patient care.
 

AGA’s commitment to early-career investigators

The Editorial Fellowship allowed me to expand a traditional third-year gastroenterology fellowship to dive deep into the intense path to get a manuscript published in Gastroenterology. Whereas 1 year prior, I had found dilating a complete esophageal stricture difficult, I now found myself learning to master clinical trial design, applying modern techniques of artificial intelligence, understanding organoid development, and navigating the impact of the microbiome. I was fortunate to be selected for Vanderbilt’s Master’s in Science in Clinical Investigation, which allowed me to apply my education not only to my own research but also to synergistically understand and deconstruct new submissions ranging from modern statistics with Bayesian modeling to analysis of large genetic data. All of this was built in the supportive framework of my mentoring committee.

As a fellow, I am inspired to see the multicenter, international collaboration to answer important questions in our field. Leveraging large databases and the expertise of multiple investigators, breakthroughs were made because of the collaborative nature of the science. This also was felt in the review process, where experts generously reviewed manuscripts to enhance the quality of the submission in order to advance knowledge in the field. Reading hundreds of these reviews this year has allowed me to refocus my current research studies and improve the way I write my current reviews. In the spirit of reproducible science and challenging the precision of study design, I was impressed by the time, effort, and dedication reviewers from our field spent to help improve the literature. Dr. Peek and Dr. Corley, our editors in chief, committed their time in discussing my innovations and critiques and displayed their level of interest in the opinions of early-career investigators and fostering the next generation of scientists and practitioners. In this lesson, I was invigorated by the depth of AGA opportunities for fellows and junior faculty in education, research, and involvement.
 

Self-reflection

Having the honor and privilege to review manuscripts upon submission also increased my critical view of my current practices. I now question the level of evidence for which current patient care practices are based, which allows me to better understand the research areas that need increased attention to improve the quality of our guidelines and evidence. For motivated fellows interested in a path of academic medicine, I would strongly advise applying for this prestigious fellowship. In no other training process could I have learned such a breadth of scientific skills and directly apply them to my patient care, my research, and my role as an educator. Furthermore, I was able to contribute to the reviewing and editing process, which allowed me to directly contribute to the field at an early stage of my career. In this final lesson, I exit this impactful Editorial Fellowship in self-reflection. I leave this fellowship humbled – by you – the reader who continues to learn to improve your patient care, the scientist as she works tirelessly to answer questions and contribute to the literature, the gastroenterology community for their willingness to teach and mentor fellows and early-career investigators and practitioners, and the patients who remind us that we all have a shared mission to advance scientific knowledge to improve patient care.

Dr. Naik is a gastroenterology fellow in the department of gastroenterology and hepatology at Vanderbilt University Medical Center in Nashville, Tenn.

Reference

1. Shah ED. Skills acquired during my 1-year AGA Editorial Fellowship. Gastroenterology. 2018;154(6):1563.

As medical professionals, you may have encountered patients with serious illnesses and asked yourself the following questions: What if I was in that situation? Where will my assets go when I die? What will happen to my loved ones, and will they be taken care of? Who would handle my affairs if I became ill? These important questions can only be addressed through effective estate planning.

Everyone needs an estate plan regardless of age, health, and financial or family situation. An effective estate plan provides for the orderly management and disposition of your assets upon your death. In addition, as medical professionals may appreciate, an effective estate plan appoints individuals to manage your financial affairs and make health care decisions for you in the event that you become physically or mentally incapacitated.

The most common estate planning tool is a will, which dictates how your assets pass at death. In addition, a will identifies the personal representative of your estate (that is, the person who will see that your assets pass in accordance with your wishes) and, in many states, identifies the guardian of any minor children. Although a court will make the ultimate determination of who is appointed as the guardian, courts typically give significant weight to the person named in a will.

If you die “intestate,” meaning that you died without a valid will, your assets will be distributed in accordance with your state’s intestacy statutes, and any interested person (as opposed to the individual of your choice) may be appointed as the personal representative of your estate. Therefore, to ensure that your property goes to the individuals of your choice and that your final affairs are handled by the person you trust, a will is essential.

In many states, a revocable living trust can be equally beneficial. Like a will, a revocable living trust will dictate how your property passes at death and appoints a trustee to see that the property is distributed in accordance with your wishes. Revocable living trusts can be great tools for incapacity planning and, unlike a will, are not required to be recorded, so the trust agreement can remain private. The assets that are held in a revocable living trust also avoid the often lengthy and expensive probate process, which generally includes the preparation and filing of a petition to open the estate, an inventory identifying the assets of the estate, and an accounting that details all assets received and distributed, followed by the payment of fees based upon the value of the probate estate.

In many situations, leaving assets to young, disabled, or troubled children would result in catastrophic consequences, such as disqualification for government benefits, dissipation of assets for inappropriate uses, or attachment by creditors. Further, for wealthy individuals, outright distributions to spouses could lead to unnecessary estate tax. Wills and revocable trusts can protect against these issues by requiring that, at death, the decedent’s assets are held in further trust for these individuals.

There are various types of trusts that can help ensure that your assets are used for the benefit of your loved one while avoiding any unintended consequences, some of which include the following:

• Special needs trusts, which allow the trustee to use the trust funds for the benefit of the disabled beneficiary without disqualifying the beneficiary from important government benefits.
• Spendthrift trusts, which can protect the trust assets from claims of creditors or property division in a divorce action.
• Marital trusts, which can be used to reduce taxes and ensure that property will be distributed pursuant to your wishes upon the death of your spouse.
• Dynasty trusts, which can be used to protect assets for many generations and, in doing so, reduce the amount of federal and state transfer taxes.

Whether you use a will or revocable living trust, it is critical to coordinate the beneficiary designations of assets such as retirement accounts and life insurance policies, as well as any other account that passes by beneficiary designation. These beneficiary designations trump the provisions of your will and revocable living trust. Likewise, property owned jointly with another person as joint tenants with the right of survivorship, or with a spouse as tenants by the entirety, will pass directly to the joint owner and not pursuant to the terms of your will or revocable trust.

An effective estate plan involves not just planning for death, but also for your incapacity. A durable power of attorney allows you to select an agent or agents to manage your property during your lifetime. The power of attorney can become effective immediately so that the agent can act on your behalf upon execution of the document or the power of attorney can become effective only if and when you become incapacitated.

A durable power of attorney for health care (or advance health care directive) permits you to appoint an agent to make health care decisions on your behalf in the event that you cannot make your own decisions. In addition, should you become permanently unconscious or in a terminal condition, it permits you to appoint an agent who can withhold or withdraw life-sustaining treatment. With a living will, you can express in writing the circumstances under which you do or do not want artificial life-sustaining measures.

With respect to these powers of attorney, the persons that you appoint as your agents should be people that you trust. It is also important to have conversations with your designated agents to ensure that they understand their responsibilities and your wishes. Without these powers of attorney, in the event of your incapacitation, a court will appoint a guardian. The guardian may not be the person you would have appointed, and it will result in annual, and burdensome, court filings.

As busy medical professionals, it may be difficult to find time to develop an estate plan and you may believe that there is plenty of time to do it in the future. It is important to begin thinking about your estate-planning goals and to speak with an attorney to help develop and draft your estate-planning documents. If you already have estate-planning documents, it is important to review those documents periodically to ensure that your estate-planning objectives have remained the same and, if they have changed, to update your documents.

No one knows what the future will hold, so it is important to consult with a local attorney to establish or review your estate plan now. If you do, you will be comforted by the fact that you and your loved ones will be taken care of in accordance with your wishes if you are unable to do so in the future.
 

Mr. D’Emilio is a managing member and Mr. Riley is an associate at McCollom D’Emilio Smith Uebler, Wilmington, Del.

As medical professionals, you may have encountered patients with serious illnesses and asked yourself the following questions: What if I was in that situation? Where will my assets go when I die? What will happen to my loved ones, and will they be taken care of? Who would handle my affairs if I became ill? These important questions can only be addressed through effective estate planning.

Everyone needs an estate plan regardless of age, health, and financial or family situation. An effective estate plan provides for the orderly management and disposition of your assets upon your death. In addition, as medical professionals may appreciate, an effective estate plan appoints individuals to manage your financial affairs and make health care decisions for you in the event that you become physically or mentally incapacitated.

The most common estate planning tool is a will, which dictates how your assets pass at death. In addition, a will identifies the personal representative of your estate (that is, the person who will see that your assets pass in accordance with your wishes) and, in many states, identifies the guardian of any minor children. Although a court will make the ultimate determination of who is appointed as the guardian, courts typically give significant weight to the person named in a will.

If you die “intestate,” meaning that you died without a valid will, your assets will be distributed in accordance with your state’s intestacy statutes, and any interested person (as opposed to the individual of your choice) may be appointed as the personal representative of your estate. Therefore, to ensure that your property goes to the individuals of your choice and that your final affairs are handled by the person you trust, a will is essential.

In many states, a revocable living trust can be equally beneficial. Like a will, a revocable living trust will dictate how your property passes at death and appoints a trustee to see that the property is distributed in accordance with your wishes. Revocable living trusts can be great tools for incapacity planning and, unlike a will, are not required to be recorded, so the trust agreement can remain private. The assets that are held in a revocable living trust also avoid the often lengthy and expensive probate process, which generally includes the preparation and filing of a petition to open the estate, an inventory identifying the assets of the estate, and an accounting that details all assets received and distributed, followed by the payment of fees based upon the value of the probate estate.

In many situations, leaving assets to young, disabled, or troubled children would result in catastrophic consequences, such as disqualification for government benefits, dissipation of assets for inappropriate uses, or attachment by creditors. Further, for wealthy individuals, outright distributions to spouses could lead to unnecessary estate tax. Wills and revocable trusts can protect against these issues by requiring that, at death, the decedent’s assets are held in further trust for these individuals.

There are various types of trusts that can help ensure that your assets are used for the benefit of your loved one while avoiding any unintended consequences, some of which include the following:

• Special needs trusts, which allow the trustee to use the trust funds for the benefit of the disabled beneficiary without disqualifying the beneficiary from important government benefits.
• Spendthrift trusts, which can protect the trust assets from claims of creditors or property division in a divorce action.
• Marital trusts, which can be used to reduce taxes and ensure that property will be distributed pursuant to your wishes upon the death of your spouse.
• Dynasty trusts, which can be used to protect assets for many generations and, in doing so, reduce the amount of federal and state transfer taxes.

Whether you use a will or revocable living trust, it is critical to coordinate the beneficiary designations of assets such as retirement accounts and life insurance policies, as well as any other account that passes by beneficiary designation. These beneficiary designations trump the provisions of your will and revocable living trust. Likewise, property owned jointly with another person as joint tenants with the right of survivorship, or with a spouse as tenants by the entirety, will pass directly to the joint owner and not pursuant to the terms of your will or revocable trust.

An effective estate plan involves not just planning for death, but also for your incapacity. A durable power of attorney allows you to select an agent or agents to manage your property during your lifetime. The power of attorney can become effective immediately so that the agent can act on your behalf upon execution of the document or the power of attorney can become effective only if and when you become incapacitated.

A durable power of attorney for health care (or advance health care directive) permits you to appoint an agent to make health care decisions on your behalf in the event that you cannot make your own decisions. In addition, should you become permanently unconscious or in a terminal condition, it permits you to appoint an agent who can withhold or withdraw life-sustaining treatment. With a living will, you can express in writing the circumstances under which you do or do not want artificial life-sustaining measures.

With respect to these powers of attorney, the persons that you appoint as your agents should be people that you trust. It is also important to have conversations with your designated agents to ensure that they understand their responsibilities and your wishes. Without these powers of attorney, in the event of your incapacitation, a court will appoint a guardian. The guardian may not be the person you would have appointed, and it will result in annual, and burdensome, court filings.

As busy medical professionals, it may be difficult to find time to develop an estate plan and you may believe that there is plenty of time to do it in the future. It is important to begin thinking about your estate-planning goals and to speak with an attorney to help develop and draft your estate-planning documents. If you already have estate-planning documents, it is important to review those documents periodically to ensure that your estate-planning objectives have remained the same and, if they have changed, to update your documents.

No one knows what the future will hold, so it is important to consult with a local attorney to establish or review your estate plan now. If you do, you will be comforted by the fact that you and your loved ones will be taken care of in accordance with your wishes if you are unable to do so in the future.
 

Mr. D’Emilio is a managing member and Mr. Riley is an associate at McCollom D’Emilio Smith Uebler, Wilmington, Del.

As medical professionals, you may have encountered patients with serious illnesses and asked yourself the following questions: What if I was in that situation? Where will my assets go when I die? What will happen to my loved ones, and will they be taken care of? Who would handle my affairs if I became ill? These important questions can only be addressed through effective estate planning.

Everyone needs an estate plan regardless of age, health, and financial or family situation. An effective estate plan provides for the orderly management and disposition of your assets upon your death. In addition, as medical professionals may appreciate, an effective estate plan appoints individuals to manage your financial affairs and make health care decisions for you in the event that you become physically or mentally incapacitated.

The most common estate planning tool is a will, which dictates how your assets pass at death. In addition, a will identifies the personal representative of your estate (that is, the person who will see that your assets pass in accordance with your wishes) and, in many states, identifies the guardian of any minor children. Although a court will make the ultimate determination of who is appointed as the guardian, courts typically give significant weight to the person named in a will.

If you die “intestate,” meaning that you died without a valid will, your assets will be distributed in accordance with your state’s intestacy statutes, and any interested person (as opposed to the individual of your choice) may be appointed as the personal representative of your estate. Therefore, to ensure that your property goes to the individuals of your choice and that your final affairs are handled by the person you trust, a will is essential.

In many states, a revocable living trust can be equally beneficial. Like a will, a revocable living trust will dictate how your property passes at death and appoints a trustee to see that the property is distributed in accordance with your wishes. Revocable living trusts can be great tools for incapacity planning and, unlike a will, are not required to be recorded, so the trust agreement can remain private. The assets that are held in a revocable living trust also avoid the often lengthy and expensive probate process, which generally includes the preparation and filing of a petition to open the estate, an inventory identifying the assets of the estate, and an accounting that details all assets received and distributed, followed by the payment of fees based upon the value of the probate estate.

In many situations, leaving assets to young, disabled, or troubled children would result in catastrophic consequences, such as disqualification for government benefits, dissipation of assets for inappropriate uses, or attachment by creditors. Further, for wealthy individuals, outright distributions to spouses could lead to unnecessary estate tax. Wills and revocable trusts can protect against these issues by requiring that, at death, the decedent’s assets are held in further trust for these individuals.

There are various types of trusts that can help ensure that your assets are used for the benefit of your loved one while avoiding any unintended consequences, some of which include the following:

• Special needs trusts, which allow the trustee to use the trust funds for the benefit of the disabled beneficiary without disqualifying the beneficiary from important government benefits.
• Spendthrift trusts, which can protect the trust assets from claims of creditors or property division in a divorce action.
• Marital trusts, which can be used to reduce taxes and ensure that property will be distributed pursuant to your wishes upon the death of your spouse.
• Dynasty trusts, which can be used to protect assets for many generations and, in doing so, reduce the amount of federal and state transfer taxes.

Whether you use a will or revocable living trust, it is critical to coordinate the beneficiary designations of assets such as retirement accounts and life insurance policies, as well as any other account that passes by beneficiary designation. These beneficiary designations trump the provisions of your will and revocable living trust. Likewise, property owned jointly with another person as joint tenants with the right of survivorship, or with a spouse as tenants by the entirety, will pass directly to the joint owner and not pursuant to the terms of your will or revocable trust.

An effective estate plan involves not just planning for death, but also for your incapacity. A durable power of attorney allows you to select an agent or agents to manage your property during your lifetime. The power of attorney can become effective immediately so that the agent can act on your behalf upon execution of the document or the power of attorney can become effective only if and when you become incapacitated.

A durable power of attorney for health care (or advance health care directive) permits you to appoint an agent to make health care decisions on your behalf in the event that you cannot make your own decisions. In addition, should you become permanently unconscious or in a terminal condition, it permits you to appoint an agent who can withhold or withdraw life-sustaining treatment. With a living will, you can express in writing the circumstances under which you do or do not want artificial life-sustaining measures.

With respect to these powers of attorney, the persons that you appoint as your agents should be people that you trust. It is also important to have conversations with your designated agents to ensure that they understand their responsibilities and your wishes. Without these powers of attorney, in the event of your incapacitation, a court will appoint a guardian. The guardian may not be the person you would have appointed, and it will result in annual, and burdensome, court filings.

As busy medical professionals, it may be difficult to find time to develop an estate plan and you may believe that there is plenty of time to do it in the future. It is important to begin thinking about your estate-planning goals and to speak with an attorney to help develop and draft your estate-planning documents. If you already have estate-planning documents, it is important to review those documents periodically to ensure that your estate-planning objectives have remained the same and, if they have changed, to update your documents.

No one knows what the future will hold, so it is important to consult with a local attorney to establish or review your estate plan now. If you do, you will be comforted by the fact that you and your loved ones will be taken care of in accordance with your wishes if you are unable to do so in the future.
 

Mr. D’Emilio is a managing member and Mr. Riley is an associate at McCollom D’Emilio Smith Uebler, Wilmington, Del.

Clinical question: Is physician burnout associated with more patient safety issues, low professionalism, or poor patient satisfaction?

Background: Burnout is common among physicians and has a negative effect on their personal lives. It is unclear whether physician burnout is associated with poor outcomes for patients.

Study design: Meta-analysis.

Setting: Forty-seven published studies from 19 countries assessing inpatient and outpatient physicians and the relationship between physician burnout and patient care.

Synopsis: After a systematic review of the published literature, 47 studies were included to pool data from 42,473 physicians. Study subjects included residents, early-career and late-career physicians, and both hospital and outpatient physicians. All studies used validated measures of physician burnout.

Burnout was associated with a two-fold increased risk of physician-reported safety incidents (odds ratio, 1.96; 95% confidence interval, 1.59-2.40), low professionalism (OR, 2.31; 95% CI, 1.87-2.85), and likelihood of low patient-reported satisfaction (OR, 2.28; 95% CI, 1.42-3.68). There were no significant differences in these results based on country of origin of the study. Early-career physicians were more likely to have burnout associated with low professionalism than were late-career physicians.

Of the components of burnout, depersonalization was most strongly associated with these negative outcomes. Interestingly, the increased risk of patient safety incidents was associated with physician-reported, but not health care system–reported, patient safety outcomes. This raises concerns that the health care systems may not be capturing “near misses” in their metrics.

Bottom line: Physician burnout doubles the risk of being involved in a patient safety incident, low professionalism, and poor patient satisfaction.

Citation: Panagioti M et al. Association between physician burnout and patient safety, professionalism, and patient satisfaction. JAMA Intern Med. 2018;178(10):1317-30.
 

Dr. Gabriel is assistant professor of medicine and director of Pre-operative Medicine and Medicine Consult Service in the division of hospital medicine at Mount Sinai Hospital, New York.

Clinical question: Is physician burnout associated with more patient safety issues, low professionalism, or poor patient satisfaction?

Background: Burnout is common among physicians and has a negative effect on their personal lives. It is unclear whether physician burnout is associated with poor outcomes for patients.

Study design: Meta-analysis.

Setting: Forty-seven published studies from 19 countries assessing inpatient and outpatient physicians and the relationship between physician burnout and patient care.

Synopsis: After a systematic review of the published literature, 47 studies were included to pool data from 42,473 physicians. Study subjects included residents, early-career and late-career physicians, and both hospital and outpatient physicians. All studies used validated measures of physician burnout.

Burnout was associated with a two-fold increased risk of physician-reported safety incidents (odds ratio, 1.96; 95% confidence interval, 1.59-2.40), low professionalism (OR, 2.31; 95% CI, 1.87-2.85), and likelihood of low patient-reported satisfaction (OR, 2.28; 95% CI, 1.42-3.68). There were no significant differences in these results based on country of origin of the study. Early-career physicians were more likely to have burnout associated with low professionalism than were late-career physicians.

Of the components of burnout, depersonalization was most strongly associated with these negative outcomes. Interestingly, the increased risk of patient safety incidents was associated with physician-reported, but not health care system–reported, patient safety outcomes. This raises concerns that the health care systems may not be capturing “near misses” in their metrics.

Bottom line: Physician burnout doubles the risk of being involved in a patient safety incident, low professionalism, and poor patient satisfaction.

Citation: Panagioti M et al. Association between physician burnout and patient safety, professionalism, and patient satisfaction. JAMA Intern Med. 2018;178(10):1317-30.
 

Dr. Gabriel is assistant professor of medicine and director of Pre-operative Medicine and Medicine Consult Service in the division of hospital medicine at Mount Sinai Hospital, New York.

Clinical question: Is physician burnout associated with more patient safety issues, low professionalism, or poor patient satisfaction?

Background: Burnout is common among physicians and has a negative effect on their personal lives. It is unclear whether physician burnout is associated with poor outcomes for patients.

Study design: Meta-analysis.

Setting: Forty-seven published studies from 19 countries assessing inpatient and outpatient physicians and the relationship between physician burnout and patient care.

Synopsis: After a systematic review of the published literature, 47 studies were included to pool data from 42,473 physicians. Study subjects included residents, early-career and late-career physicians, and both hospital and outpatient physicians. All studies used validated measures of physician burnout.

Burnout was associated with a two-fold increased risk of physician-reported safety incidents (odds ratio, 1.96; 95% confidence interval, 1.59-2.40), low professionalism (OR, 2.31; 95% CI, 1.87-2.85), and likelihood of low patient-reported satisfaction (OR, 2.28; 95% CI, 1.42-3.68). There were no significant differences in these results based on country of origin of the study. Early-career physicians were more likely to have burnout associated with low professionalism than were late-career physicians.

Of the components of burnout, depersonalization was most strongly associated with these negative outcomes. Interestingly, the increased risk of patient safety incidents was associated with physician-reported, but not health care system–reported, patient safety outcomes. This raises concerns that the health care systems may not be capturing “near misses” in their metrics.

Bottom line: Physician burnout doubles the risk of being involved in a patient safety incident, low professionalism, and poor patient satisfaction.

Citation: Panagioti M et al. Association between physician burnout and patient safety, professionalism, and patient satisfaction. JAMA Intern Med. 2018;178(10):1317-30.
 

Dr. Gabriel is assistant professor of medicine and director of Pre-operative Medicine and Medicine Consult Service in the division of hospital medicine at Mount Sinai Hospital, New York.

The treatment of psoriasis in patients with HIV infection represents a clinical challenge.^1,2 Up to 3% of patients with HIV infection are estimated to have psoriasis. Although this prevalence is similar to the general population, psoriatic disease in patients with HIV tends to be more severe, refractory, and more difficult to treat.^3-5 Additionally, up to half of patients with comorbid HIV and psoriasis also have substantial psoriatic arthritis (PsA).^1,6 

Drug treatments for psoriasis and PsA often are immunosuppressive; as such, the treatment of psoriasis in this patient population requires careful consideration of the potential risks and benefits of treatment as well as fastidious monitoring for the emergence of potentially adverse treatment effects.¹ A careful diagnostic process to determine the severity of HIV-associated psoriasis and to select the appropriate treatment relative to the patient’s immunologic status is of critical importance.³ 

Presentation of Psoriasis in Patients With HIV Infection

The presentation and severity of psoriasis in patients with HIV infection is highly variable and is often related to the degree of immune suppression experienced by the patient.^3,7 In some individuals, psoriasis may be the first outward manifestation of HIV, whereas in others, it only manifests after HIV has progressed to AIDS.⁷ 

Recognition of the atypical presentations of psoriasis that are frequently seen in patients with HIV infection can help to facilitate early diagnosis and treatment to improve patient outcomes.^3,8 Psoriasis vulgaris, for example, typically presents as erythematous plaques with silvery-white scales on extensor surfaces of the body such as the knees and elbows. However, in patients with HIV, psoriasis vulgaris may present with scales that appear thick and oyster shell–like instead of silvery-white; these lesions also may occur on flexural areas rather than extensor surfaces.⁸ Similarly, the sudden onset of widespread psoriasis in otherwise healthy persons should trigger suspicion for HIV infection and recommendations for appropriate testing, even when no risk factors are present.⁸ 

Guttate, inverse, and erythrodermic psoriasis are the most common subtypes in patients with HIV infection, though all clinical subtypes may occur. Overlapping of psoriasis subtypes often occurs in individuals with HIV infection and should serve as a red flag to recommend screening for HIV.^5,8 Acral involvement, frequently with pustules and occasionally with severe destructive nail changes, is commonly seen in patients with HIV-associated psoriasis.^7,9 In cases involving severe psoriatic exacerbations among individuals with AIDS, there is a heightened risk of developing systemic infections, including superinfection of Staphylococcus aureus, which is a rare occurrence in immunocompetent patients with psoriasis.^7,10,11 

Therapeutic Options

Because the clinical course of psoriasis in patients with HIV infection is frequently progressive and refractory to treatment, traditional first- and second-line therapies (Table) including topical agents, phototherapy, and oral retinoids may be unable to achieve lasting control of both skin and joint manifestations.¹ 

Topical Therapy

As in the general population, targeted therapies such as topical agents are recommended as first-line treatment of mild HIV-associated psoriasis.¹² Topical corticosteroids, calcipotriol, tazarotene, and formulations combining 2 of these medications form the cornerstone of topical therapies for mild psoriasis in patients with HIV infection. These agents have the advantage of possessing limited and localized effects, making it unlikely for them to increase immunosuppression in patients with HIV infection. They generally can be safely used in patients with HIV infection, and their side-effect profile in patients with HIV infection is similar to the general population.¹² However, calcipotriol is the least desirable for use in patients with hypertriglyceridemia, which can be a side effect of antiretroviral drugs.⁴ 

UV Phototherapy

Topical therapy is limited by its lack of potency; limited field coverage; and the inconvenience of application, particularly in patients with more widespread disease.¹² Therefore, UV phototherapy is preferred as first-line treatment of moderate to severe psoriasis. UV phototherapy has been shown to inhibit cell proliferation and inflammation and result in clinical improvement of HIV-associated psoriasis; moreover, most of the reports in the literature support it as an option that will not increase immunocompromise in patients with HIV infection.¹² 

Caution is warranted, however, regarding the immunomodulatory effects of UV therapies, which may result in an increased risk for skin cancer and diminished resistance to infection, which can be of particular concern in immunocompromised patients who are already at risk.^7,13,14 In patients who are candidates for phototherapy, HIV serology and close monitoring of viral load and CD4 lymphocyte count before treatment, at monthly interludes throughout treatment, and 3 months following the cessation of treatment have been recommended.^7,15 Careful consideration of the risk-benefit ratio of phototherapy for individual patients, including the patient’s stage of HIV disease, the degree of discomfort, disfigurement, and disability caused by the psoriasis (or other dermatologic condition), as well as the availability of alternative treatment options is essential.^7,16 

Systemic Agents

In patients who are intolerant of or unresponsive to antiretroviral therapy, topical therapies, and phototherapy, traditional systemic agents may be considered,¹² including acitretin, methotrexate, and cyclosporine. However, updated guidelines indicate that methotrexate and cyclosporine should be avoided in this population given the risk for increased immunosuppression with these agents.^4,17 

Oral retinoids, such as acitretin, continue to be important options for second-line psoriasis treatment in patients with comorbid HIV infection, either as monotherapy or in association with phototherapy.³ Acitretin has the notable benefit of not causing or worsening immune compromise; however, its use is less than desirable in patients with hypertriglyceridemia, which can be a side effect of antiretroviral drugs.^4,12 Providers also must be aware of the possible association between acitretin (and other antiretrovirals) and pancreatitis, remaining vigilant in monitoring patients for this adverse effect.³ 

Biologics

The relatively recent addition of cytokine-suppressive biologic agents to the treatment armamentarium has transformed the management of psoriasis in otherwise healthy individuals. These agents have been shown to possess an excellent safety and efficacy profile.¹² However, their use in patients with HIV infection has been mired in concerns regarding a potential increase in the risk for opportunistic infections, sepsis, and HIV disease progression in this patient population.^7,12 

Case reports have detailed the safe treatment of recalcitrant HIV-associated psoriasis with tumor necrosis factor (TNF) blockers, such as etanercept.^7,12 In most of these case reports, no harm to CD4 lymphocyte counts, serum viral loads, overall immune status, and susceptibility to infection have been noted; on the contrary, CD4 count increased in most patients following treatment with biologic agents.¹² Because patients with HIV infection tend to be excluded from clinical trials, anecdotal evidence derived from case reports and case series often provides clinically relevant information and often forms the basis for treatment recommendations in this patient population.¹² Indeed, in the wake of positive case reports, TNF-α inhibitors are now recommended for highly selected patients with refractory chronic psoriatic disease, including those with incapacitating joint pain.^7,18 

When TNF-α inhibitors are used in patients with HIV infection and psoriasis, optimal antiretroviral therapy and exceedingly close monitoring of clinical and laboratory parameters are of the utmost importance; Pneumocystis jiroveci prophylaxis also is recommended in patients with low CD4 counts.^7,18 

In 2014, the oral phosphodiesterase 4 inhibitor apremilast was approved for the treatment of moderate to severe plaque psoriasis and PsA. Recent case reports have described its successful use in patients with HIV infection and psoriasis, including the case reported herein, with no reports of opportunistic infections.^4,19 Furthermore, HIV infection is not listed as a contraindication on its label.²⁰

Apremilast is thought to increase intracellular cyclic adenosine monophosphate, thereby helping to attain improved homeostasis between proinflammatory and anti-inflammatory mediators.^4,19 Several of the proinflammatory mediators that are indirectly targeted by apremilast, including TNF-α and IL-23, are explicitly inhibited by other biologics. It is this equilibrium between proinflammatory and anti-inflammatory mediators that most markedly differentiates apremilast from most other available biologic therapies for psoriasis, which typically have a specific proinflammatory target.^4,21 As with other systemic therapies, close monitoring of CD4 levels and viral loads, as well as use of relevant prophylactic agents, is essential when apremilast is used in the setting of HIV infection, making coordination with infectious disease specialists essential.¹⁹ 

Bottom Line

Management of psoriasis in patients with HIV infection represents a clinical challenge. Case reports suggest a role for apremilast as an adjuvant to first-line therapy such as UV phototherapy in the setting of HIV infection in a patient with moderate to severe psoriasis, but close monitoring of CD4 count and viral load in these patients is needed in collaboration with infectious disease specialists. Updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population are needed. 

The treatment of psoriasis in patients with HIV infection represents a clinical challenge.^1,2 Up to 3% of patients with HIV infection are estimated to have psoriasis. Although this prevalence is similar to the general population, psoriatic disease in patients with HIV tends to be more severe, refractory, and more difficult to treat.^3-5 Additionally, up to half of patients with comorbid HIV and psoriasis also have substantial psoriatic arthritis (PsA).^1,6 

Drug treatments for psoriasis and PsA often are immunosuppressive; as such, the treatment of psoriasis in this patient population requires careful consideration of the potential risks and benefits of treatment as well as fastidious monitoring for the emergence of potentially adverse treatment effects.¹ A careful diagnostic process to determine the severity of HIV-associated psoriasis and to select the appropriate treatment relative to the patient’s immunologic status is of critical importance.³ 

Presentation of Psoriasis in Patients With HIV Infection

The presentation and severity of psoriasis in patients with HIV infection is highly variable and is often related to the degree of immune suppression experienced by the patient.^3,7 In some individuals, psoriasis may be the first outward manifestation of HIV, whereas in others, it only manifests after HIV has progressed to AIDS.⁷ 

Recognition of the atypical presentations of psoriasis that are frequently seen in patients with HIV infection can help to facilitate early diagnosis and treatment to improve patient outcomes.^3,8 Psoriasis vulgaris, for example, typically presents as erythematous plaques with silvery-white scales on extensor surfaces of the body such as the knees and elbows. However, in patients with HIV, psoriasis vulgaris may present with scales that appear thick and oyster shell–like instead of silvery-white; these lesions also may occur on flexural areas rather than extensor surfaces.⁸ Similarly, the sudden onset of widespread psoriasis in otherwise healthy persons should trigger suspicion for HIV infection and recommendations for appropriate testing, even when no risk factors are present.⁸ 

Guttate, inverse, and erythrodermic psoriasis are the most common subtypes in patients with HIV infection, though all clinical subtypes may occur. Overlapping of psoriasis subtypes often occurs in individuals with HIV infection and should serve as a red flag to recommend screening for HIV.^5,8 Acral involvement, frequently with pustules and occasionally with severe destructive nail changes, is commonly seen in patients with HIV-associated psoriasis.^7,9 In cases involving severe psoriatic exacerbations among individuals with AIDS, there is a heightened risk of developing systemic infections, including superinfection of Staphylococcus aureus, which is a rare occurrence in immunocompetent patients with psoriasis.^7,10,11 

Therapeutic Options

Because the clinical course of psoriasis in patients with HIV infection is frequently progressive and refractory to treatment, traditional first- and second-line therapies (Table) including topical agents, phototherapy, and oral retinoids may be unable to achieve lasting control of both skin and joint manifestations.¹ 

Topical Therapy

As in the general population, targeted therapies such as topical agents are recommended as first-line treatment of mild HIV-associated psoriasis.¹² Topical corticosteroids, calcipotriol, tazarotene, and formulations combining 2 of these medications form the cornerstone of topical therapies for mild psoriasis in patients with HIV infection. These agents have the advantage of possessing limited and localized effects, making it unlikely for them to increase immunosuppression in patients with HIV infection. They generally can be safely used in patients with HIV infection, and their side-effect profile in patients with HIV infection is similar to the general population.¹² However, calcipotriol is the least desirable for use in patients with hypertriglyceridemia, which can be a side effect of antiretroviral drugs.⁴ 

UV Phototherapy

Topical therapy is limited by its lack of potency; limited field coverage; and the inconvenience of application, particularly in patients with more widespread disease.¹² Therefore, UV phototherapy is preferred as first-line treatment of moderate to severe psoriasis. UV phototherapy has been shown to inhibit cell proliferation and inflammation and result in clinical improvement of HIV-associated psoriasis; moreover, most of the reports in the literature support it as an option that will not increase immunocompromise in patients with HIV infection.¹² 

Caution is warranted, however, regarding the immunomodulatory effects of UV therapies, which may result in an increased risk for skin cancer and diminished resistance to infection, which can be of particular concern in immunocompromised patients who are already at risk.^7,13,14 In patients who are candidates for phototherapy, HIV serology and close monitoring of viral load and CD4 lymphocyte count before treatment, at monthly interludes throughout treatment, and 3 months following the cessation of treatment have been recommended.^7,15 Careful consideration of the risk-benefit ratio of phototherapy for individual patients, including the patient’s stage of HIV disease, the degree of discomfort, disfigurement, and disability caused by the psoriasis (or other dermatologic condition), as well as the availability of alternative treatment options is essential.^7,16 

Systemic Agents

In patients who are intolerant of or unresponsive to antiretroviral therapy, topical therapies, and phototherapy, traditional systemic agents may be considered,¹² including acitretin, methotrexate, and cyclosporine. However, updated guidelines indicate that methotrexate and cyclosporine should be avoided in this population given the risk for increased immunosuppression with these agents.^4,17 

Oral retinoids, such as acitretin, continue to be important options for second-line psoriasis treatment in patients with comorbid HIV infection, either as monotherapy or in association with phototherapy.³ Acitretin has the notable benefit of not causing or worsening immune compromise; however, its use is less than desirable in patients with hypertriglyceridemia, which can be a side effect of antiretroviral drugs.^4,12 Providers also must be aware of the possible association between acitretin (and other antiretrovirals) and pancreatitis, remaining vigilant in monitoring patients for this adverse effect.³ 

Biologics

The relatively recent addition of cytokine-suppressive biologic agents to the treatment armamentarium has transformed the management of psoriasis in otherwise healthy individuals. These agents have been shown to possess an excellent safety and efficacy profile.¹² However, their use in patients with HIV infection has been mired in concerns regarding a potential increase in the risk for opportunistic infections, sepsis, and HIV disease progression in this patient population.^7,12 

Case reports have detailed the safe treatment of recalcitrant HIV-associated psoriasis with tumor necrosis factor (TNF) blockers, such as etanercept.^7,12 In most of these case reports, no harm to CD4 lymphocyte counts, serum viral loads, overall immune status, and susceptibility to infection have been noted; on the contrary, CD4 count increased in most patients following treatment with biologic agents.¹² Because patients with HIV infection tend to be excluded from clinical trials, anecdotal evidence derived from case reports and case series often provides clinically relevant information and often forms the basis for treatment recommendations in this patient population.¹² Indeed, in the wake of positive case reports, TNF-α inhibitors are now recommended for highly selected patients with refractory chronic psoriatic disease, including those with incapacitating joint pain.^7,18 

When TNF-α inhibitors are used in patients with HIV infection and psoriasis, optimal antiretroviral therapy and exceedingly close monitoring of clinical and laboratory parameters are of the utmost importance; Pneumocystis jiroveci prophylaxis also is recommended in patients with low CD4 counts.^7,18 

In 2014, the oral phosphodiesterase 4 inhibitor apremilast was approved for the treatment of moderate to severe plaque psoriasis and PsA. Recent case reports have described its successful use in patients with HIV infection and psoriasis, including the case reported herein, with no reports of opportunistic infections.^4,19 Furthermore, HIV infection is not listed as a contraindication on its label.²⁰

Apremilast is thought to increase intracellular cyclic adenosine monophosphate, thereby helping to attain improved homeostasis between proinflammatory and anti-inflammatory mediators.^4,19 Several of the proinflammatory mediators that are indirectly targeted by apremilast, including TNF-α and IL-23, are explicitly inhibited by other biologics. It is this equilibrium between proinflammatory and anti-inflammatory mediators that most markedly differentiates apremilast from most other available biologic therapies for psoriasis, which typically have a specific proinflammatory target.^4,21 As with other systemic therapies, close monitoring of CD4 levels and viral loads, as well as use of relevant prophylactic agents, is essential when apremilast is used in the setting of HIV infection, making coordination with infectious disease specialists essential.¹⁹ 

Bottom Line

Management of psoriasis in patients with HIV infection represents a clinical challenge. Case reports suggest a role for apremilast as an adjuvant to first-line therapy such as UV phototherapy in the setting of HIV infection in a patient with moderate to severe psoriasis, but close monitoring of CD4 count and viral load in these patients is needed in collaboration with infectious disease specialists. Updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population are needed. 

The treatment of psoriasis in patients with HIV infection represents a clinical challenge.^1,2 Up to 3% of patients with HIV infection are estimated to have psoriasis. Although this prevalence is similar to the general population, psoriatic disease in patients with HIV tends to be more severe, refractory, and more difficult to treat.^3-5 Additionally, up to half of patients with comorbid HIV and psoriasis also have substantial psoriatic arthritis (PsA).^1,6 

Drug treatments for psoriasis and PsA often are immunosuppressive; as such, the treatment of psoriasis in this patient population requires careful consideration of the potential risks and benefits of treatment as well as fastidious monitoring for the emergence of potentially adverse treatment effects.¹ A careful diagnostic process to determine the severity of HIV-associated psoriasis and to select the appropriate treatment relative to the patient’s immunologic status is of critical importance.³ 

Presentation of Psoriasis in Patients With HIV Infection

The presentation and severity of psoriasis in patients with HIV infection is highly variable and is often related to the degree of immune suppression experienced by the patient.^3,7 In some individuals, psoriasis may be the first outward manifestation of HIV, whereas in others, it only manifests after HIV has progressed to AIDS.⁷ 

Recognition of the atypical presentations of psoriasis that are frequently seen in patients with HIV infection can help to facilitate early diagnosis and treatment to improve patient outcomes.^3,8 Psoriasis vulgaris, for example, typically presents as erythematous plaques with silvery-white scales on extensor surfaces of the body such as the knees and elbows. However, in patients with HIV, psoriasis vulgaris may present with scales that appear thick and oyster shell–like instead of silvery-white; these lesions also may occur on flexural areas rather than extensor surfaces.⁸ Similarly, the sudden onset of widespread psoriasis in otherwise healthy persons should trigger suspicion for HIV infection and recommendations for appropriate testing, even when no risk factors are present.⁸ 

Guttate, inverse, and erythrodermic psoriasis are the most common subtypes in patients with HIV infection, though all clinical subtypes may occur. Overlapping of psoriasis subtypes often occurs in individuals with HIV infection and should serve as a red flag to recommend screening for HIV.^5,8 Acral involvement, frequently with pustules and occasionally with severe destructive nail changes, is commonly seen in patients with HIV-associated psoriasis.^7,9 In cases involving severe psoriatic exacerbations among individuals with AIDS, there is a heightened risk of developing systemic infections, including superinfection of Staphylococcus aureus, which is a rare occurrence in immunocompetent patients with psoriasis.^7,10,11 

Therapeutic Options

Because the clinical course of psoriasis in patients with HIV infection is frequently progressive and refractory to treatment, traditional first- and second-line therapies (Table) including topical agents, phototherapy, and oral retinoids may be unable to achieve lasting control of both skin and joint manifestations.¹ 

Topical Therapy

As in the general population, targeted therapies such as topical agents are recommended as first-line treatment of mild HIV-associated psoriasis.¹² Topical corticosteroids, calcipotriol, tazarotene, and formulations combining 2 of these medications form the cornerstone of topical therapies for mild psoriasis in patients with HIV infection. These agents have the advantage of possessing limited and localized effects, making it unlikely for them to increase immunosuppression in patients with HIV infection. They generally can be safely used in patients with HIV infection, and their side-effect profile in patients with HIV infection is similar to the general population.¹² However, calcipotriol is the least desirable for use in patients with hypertriglyceridemia, which can be a side effect of antiretroviral drugs.⁴ 

UV Phototherapy

Topical therapy is limited by its lack of potency; limited field coverage; and the inconvenience of application, particularly in patients with more widespread disease.¹² Therefore, UV phototherapy is preferred as first-line treatment of moderate to severe psoriasis. UV phototherapy has been shown to inhibit cell proliferation and inflammation and result in clinical improvement of HIV-associated psoriasis; moreover, most of the reports in the literature support it as an option that will not increase immunocompromise in patients with HIV infection.¹² 

Caution is warranted, however, regarding the immunomodulatory effects of UV therapies, which may result in an increased risk for skin cancer and diminished resistance to infection, which can be of particular concern in immunocompromised patients who are already at risk.^7,13,14 In patients who are candidates for phototherapy, HIV serology and close monitoring of viral load and CD4 lymphocyte count before treatment, at monthly interludes throughout treatment, and 3 months following the cessation of treatment have been recommended.^7,15 Careful consideration of the risk-benefit ratio of phototherapy for individual patients, including the patient’s stage of HIV disease, the degree of discomfort, disfigurement, and disability caused by the psoriasis (or other dermatologic condition), as well as the availability of alternative treatment options is essential.^7,16 

Systemic Agents

In patients who are intolerant of or unresponsive to antiretroviral therapy, topical therapies, and phototherapy, traditional systemic agents may be considered,¹² including acitretin, methotrexate, and cyclosporine. However, updated guidelines indicate that methotrexate and cyclosporine should be avoided in this population given the risk for increased immunosuppression with these agents.^4,17 

Oral retinoids, such as acitretin, continue to be important options for second-line psoriasis treatment in patients with comorbid HIV infection, either as monotherapy or in association with phototherapy.³ Acitretin has the notable benefit of not causing or worsening immune compromise; however, its use is less than desirable in patients with hypertriglyceridemia, which can be a side effect of antiretroviral drugs.^4,12 Providers also must be aware of the possible association between acitretin (and other antiretrovirals) and pancreatitis, remaining vigilant in monitoring patients for this adverse effect.³ 

Biologics

The relatively recent addition of cytokine-suppressive biologic agents to the treatment armamentarium has transformed the management of psoriasis in otherwise healthy individuals. These agents have been shown to possess an excellent safety and efficacy profile.¹² However, their use in patients with HIV infection has been mired in concerns regarding a potential increase in the risk for opportunistic infections, sepsis, and HIV disease progression in this patient population.^7,12 

Case reports have detailed the safe treatment of recalcitrant HIV-associated psoriasis with tumor necrosis factor (TNF) blockers, such as etanercept.^7,12 In most of these case reports, no harm to CD4 lymphocyte counts, serum viral loads, overall immune status, and susceptibility to infection have been noted; on the contrary, CD4 count increased in most patients following treatment with biologic agents.¹² Because patients with HIV infection tend to be excluded from clinical trials, anecdotal evidence derived from case reports and case series often provides clinically relevant information and often forms the basis for treatment recommendations in this patient population.¹² Indeed, in the wake of positive case reports, TNF-α inhibitors are now recommended for highly selected patients with refractory chronic psoriatic disease, including those with incapacitating joint pain.^7,18 

When TNF-α inhibitors are used in patients with HIV infection and psoriasis, optimal antiretroviral therapy and exceedingly close monitoring of clinical and laboratory parameters are of the utmost importance; Pneumocystis jiroveci prophylaxis also is recommended in patients with low CD4 counts.^7,18 

In 2014, the oral phosphodiesterase 4 inhibitor apremilast was approved for the treatment of moderate to severe plaque psoriasis and PsA. Recent case reports have described its successful use in patients with HIV infection and psoriasis, including the case reported herein, with no reports of opportunistic infections.^4,19 Furthermore, HIV infection is not listed as a contraindication on its label.²⁰

Apremilast is thought to increase intracellular cyclic adenosine monophosphate, thereby helping to attain improved homeostasis between proinflammatory and anti-inflammatory mediators.^4,19 Several of the proinflammatory mediators that are indirectly targeted by apremilast, including TNF-α and IL-23, are explicitly inhibited by other biologics. It is this equilibrium between proinflammatory and anti-inflammatory mediators that most markedly differentiates apremilast from most other available biologic therapies for psoriasis, which typically have a specific proinflammatory target.^4,21 As with other systemic therapies, close monitoring of CD4 levels and viral loads, as well as use of relevant prophylactic agents, is essential when apremilast is used in the setting of HIV infection, making coordination with infectious disease specialists essential.¹⁹ 

Bottom Line

Management of psoriasis in patients with HIV infection represents a clinical challenge. Case reports suggest a role for apremilast as an adjuvant to first-line therapy such as UV phototherapy in the setting of HIV infection in a patient with moderate to severe psoriasis, but close monitoring of CD4 count and viral load in these patients is needed in collaboration with infectious disease specialists. Updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population are needed. 

There are no benefits from vitamin D supplementation in reducing the risk of major adverse cardiovascular events or all-cause mortality, according to a meta-analysis published in JAMA Cardiology.

copyright istock/Thinkstock

Researchers analyzed data from 83,291 patients enrolled in 21 randomized, placebo-controlled clinical trials of at least 1 year of vitamin D supplementation.

They found the incidence of major adverse cardiovascular events ­was the same among patients taking vitamin D supplements and those taking placebo (risk ratio, 1; P = .85). Even stratifying by age, sex, postmenopausal status, pretreatment vitamin D levels, vitamin D dosage and formulation, chronic kidney disease, or excluding studies that used vitamin D analogues made no significant difference.

However, there was the suggestion of reduced incidence of major adverse cardiovascular events with vitamin D supplementation in individuals of advanced age, but the authors wrote that the finding should be interpreted with caution.

The analysis found no benefit from vitamin D supplementation on the secondary endpoints of MI, stroke, cardiovascular mortality, or all-cause mortality risk.


Mahmoud Barbarawi, MD, from the Hurley Medical Center at Michigan State University, East Lansing, and coauthors commented that previous observational studies have found significant associations between low vitamin D levels and cardiovascular events and all-cause mortality.

“However, observational studies are susceptible to uncontrolled confounding by outdoor physical activity, nutritional status, and prevalent chronic disease, which may influence serum 25-hydroxyvitamin D levels,” they wrote.

This updated analysis extended earlier clinical trial findings and added in some more-recent randomized trial outcomes, including the massive VITAL trial, which showed that neither daily vitamin D nor omega-3 fatty acids reduce cancer or cardiovascular event risk (N Engl J Med. 2019;380[1]:33-44).

Still, the authors noted that most of the trials included in the analysis had not prespecified cardiovascular disease as the primary endpoint and were underpowered to detect an effect on cardiovascular events. They also pointed out that few trials included data on heart failure, and a previous meta-analysis had suggested a potential benefit of supplementation in reducing the risk of this condition.

“Additional trials of higher-dose vitamin D supplementation, perhaps targeting members of older age groups and with attention to other [cardiovascular disease] endpoints such as heart failure, are of interest,” they wrote.

One author reported receiving funding from the National Institutes of Health and in-kind support from the pharmaceutical sector for a vitamin D study. No other disclosures were reported.

SOURCE: Barbarawi M et al. JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1870.

There are no benefits from vitamin D supplementation in reducing the risk of major adverse cardiovascular events or all-cause mortality, according to a meta-analysis published in JAMA Cardiology.

copyright istock/Thinkstock

Researchers analyzed data from 83,291 patients enrolled in 21 randomized, placebo-controlled clinical trials of at least 1 year of vitamin D supplementation.

They found the incidence of major adverse cardiovascular events ­was the same among patients taking vitamin D supplements and those taking placebo (risk ratio, 1; P = .85). Even stratifying by age, sex, postmenopausal status, pretreatment vitamin D levels, vitamin D dosage and formulation, chronic kidney disease, or excluding studies that used vitamin D analogues made no significant difference.

However, there was the suggestion of reduced incidence of major adverse cardiovascular events with vitamin D supplementation in individuals of advanced age, but the authors wrote that the finding should be interpreted with caution.

The analysis found no benefit from vitamin D supplementation on the secondary endpoints of MI, stroke, cardiovascular mortality, or all-cause mortality risk.


Mahmoud Barbarawi, MD, from the Hurley Medical Center at Michigan State University, East Lansing, and coauthors commented that previous observational studies have found significant associations between low vitamin D levels and cardiovascular events and all-cause mortality.

“However, observational studies are susceptible to uncontrolled confounding by outdoor physical activity, nutritional status, and prevalent chronic disease, which may influence serum 25-hydroxyvitamin D levels,” they wrote.

This updated analysis extended earlier clinical trial findings and added in some more-recent randomized trial outcomes, including the massive VITAL trial, which showed that neither daily vitamin D nor omega-3 fatty acids reduce cancer or cardiovascular event risk (N Engl J Med. 2019;380[1]:33-44).

Still, the authors noted that most of the trials included in the analysis had not prespecified cardiovascular disease as the primary endpoint and were underpowered to detect an effect on cardiovascular events. They also pointed out that few trials included data on heart failure, and a previous meta-analysis had suggested a potential benefit of supplementation in reducing the risk of this condition.

“Additional trials of higher-dose vitamin D supplementation, perhaps targeting members of older age groups and with attention to other [cardiovascular disease] endpoints such as heart failure, are of interest,” they wrote.

One author reported receiving funding from the National Institutes of Health and in-kind support from the pharmaceutical sector for a vitamin D study. No other disclosures were reported.

SOURCE: Barbarawi M et al. JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1870.

There are no benefits from vitamin D supplementation in reducing the risk of major adverse cardiovascular events or all-cause mortality, according to a meta-analysis published in JAMA Cardiology.

copyright istock/Thinkstock

Researchers analyzed data from 83,291 patients enrolled in 21 randomized, placebo-controlled clinical trials of at least 1 year of vitamin D supplementation.

They found the incidence of major adverse cardiovascular events ­was the same among patients taking vitamin D supplements and those taking placebo (risk ratio, 1; P = .85). Even stratifying by age, sex, postmenopausal status, pretreatment vitamin D levels, vitamin D dosage and formulation, chronic kidney disease, or excluding studies that used vitamin D analogues made no significant difference.

However, there was the suggestion of reduced incidence of major adverse cardiovascular events with vitamin D supplementation in individuals of advanced age, but the authors wrote that the finding should be interpreted with caution.

The analysis found no benefit from vitamin D supplementation on the secondary endpoints of MI, stroke, cardiovascular mortality, or all-cause mortality risk.


Mahmoud Barbarawi, MD, from the Hurley Medical Center at Michigan State University, East Lansing, and coauthors commented that previous observational studies have found significant associations between low vitamin D levels and cardiovascular events and all-cause mortality.

“However, observational studies are susceptible to uncontrolled confounding by outdoor physical activity, nutritional status, and prevalent chronic disease, which may influence serum 25-hydroxyvitamin D levels,” they wrote.

This updated analysis extended earlier clinical trial findings and added in some more-recent randomized trial outcomes, including the massive VITAL trial, which showed that neither daily vitamin D nor omega-3 fatty acids reduce cancer or cardiovascular event risk (N Engl J Med. 2019;380[1]:33-44).

Still, the authors noted that most of the trials included in the analysis had not prespecified cardiovascular disease as the primary endpoint and were underpowered to detect an effect on cardiovascular events. They also pointed out that few trials included data on heart failure, and a previous meta-analysis had suggested a potential benefit of supplementation in reducing the risk of this condition.

“Additional trials of higher-dose vitamin D supplementation, perhaps targeting members of older age groups and with attention to other [cardiovascular disease] endpoints such as heart failure, are of interest,” they wrote.

One author reported receiving funding from the National Institutes of Health and in-kind support from the pharmaceutical sector for a vitamin D study. No other disclosures were reported.

SOURCE: Barbarawi M et al. JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1870.